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Home Local Utah News Man arrested for alleged aggravated kidnapping, assault of his grandmother in Harrisville
Local Utah News
Man arrested for alleged aggravated kidnapping, assault of his grandmother in Harrisville
Nancy Van Valkenburg
Miguel Francisco Rendon. Photo: Weber County
HARRISVILLE, Utah, Dec. 19, 2020 (Gephardt Daily) — A 25-year-old man was booked into the Weber County jail after he allegedly held his grandmother in her residence against her will, and threatened to stab and kill her.
Miguel Francisco Rendon is being held on suspicion of:
Aggravated kidnapping, a first-degree felony
Aggravated assault, a third-degree felony
Damage/interruption of communication device, a class B misdemeanor
A probable cause statement says that on Thursday morning, a Harrisville Police officer responded to the woman's residence on a welfare check requested by her son, who lives out of state, who said his mother was being held against her will.
An officer of the Harrisville Police Department went to the address, and was not able to make contact with the victim.
"The door was locked and blinds were drawn and I was unable to see inside the
apartment," the officer said. "I heard no disturbances or any noises coming from inside the complex. I spoke with the son and established that there was no probable cause to enter the home."
About two hours later, the officer was notified the victim had arrived at the Harrisville Police Station.
"She was stating that her grandson, Miguel Rendon, had been holding her against her will inside the apartment with a knife," the probable cause statement says. "I met with the victim at the Harrisville station to conduct an interview. I was also informed that AP&P (Adult Probation & Parole) had picked up Miguel at the Burger King on 2nd Street."
The woman said Rendon had arrived at her apartment at about 6 a.m. after he got off work.
"Miguel stated to the victim that he needed to shower and rest. The victim repeatedly told Miguel that he needed to go. The victim states that an argument ensued and that Miguel also got into an argument with his father who is out of state. Miguel started to tell the victim to stop talking to his dad. Miguel then took the victims phone away from her. The victim stated that Miguel told her, she had to do what he said 'or else.'"
When the officer had arrived earlier for the welfare check, the woman said, the suspect blocked the bedroom door to prevent her from leaving to answer the door.
"The victim stated that Miguel knew the police were outside because he looked
through the blinds. After I left the apartment, the victim said that Miguel became even more agitated.
"Miguel then retrieved a knife from the kitchen. Miguel was acting very erratic and yelling at the victim. Miguel yelled at the victim that he would stab or kill someone to prove what he was saying and that she'd better listen and do what he said. The victim stated that she was in constant fear for her life and felt that she could not leave for fear Miguel would kill her."
The woman said it "is not the first time Miguel has talked or threatened her. The victim stated that during this incident, Miquel would point the knife at her putting her in fear for her safety. The victim sent a text message to Miguel's probation officer with the words 'Knife & Help' at 10:18 hours. She immediately deleted the text from her phone right as Miguel took the phone away from her preventing her from contacting any emergency services."
AP&P started to search for the victim and Rendon, but didn't have a current address, the statement says.
"The victim stated that Miguel wanted her to drive him around. According to the victim, Miguel often has the victim to drive him around for what she describes as his drug dealings. The victim stated that if she refuses, Miguel says he will kill them both in the car or he will grab the steering wheel and wreck the car. The victim states that she feels threatened by Miguel and that he will carry out his threats to prove what he is capable of doing.
"The victim felt that this would be her only way to get away from Miguel safely. The victim stated that she drove Miguel to the Burger King on 2nd street. Miguel exited the vehicle and went inside. The victim immediately left and called Miguel's probation officer."
AP&P arrived and took Rendon into custody, and transported him to jail, where he was initially booked on a probation violation, and placed on a 72-hold.
Rendon is being held without bail due to a history of drugs and drug affiliations, and because of threats made to the victim, the probable cause statement says.
Miguel Rendon
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Managing editor Nancy Van Valkenburg is an award-winning multimedia journalist with more than 30 consecutive years in the field. She has worked as a beat reporter, department head, photographer, video editor, copy editor and podcast associate producer at news outlets in Utah, Washington, Connecticut, Virginia and West Virginia.
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A COLNE Valley man is warning phone users to be on their guard after being hit with a £13 bill for a one-minute call.
Ian Ward, of Golcar, is facing the whopping charge after his 15-year-old son Ben used his mobile to call a chat-line - which is available on a standard London landline number.
The service, run by Telecom Billing Services, sends out bills to home addresses independently of BT.
Callers are charged at £12.95 for the first five minutes, no matter how long the caller stays on the line.
Mr Ward said he received a TBS bill addressed to his partner through the post for a call dated March 28 from a mobile phone.
Mr Ward, who runs a garage door business, said: "My partner doesn't personally own a mobile, so she rang the customer services number and was advised to return the bill marked 'no mobile'.
"When we looked closer the mobile number was one of our business mobiles, which had been in our possession on the night of the call.
"This mobile is registered to our company in Mirfield and we were puzzled as to how the phone had been linked to my partner's name and our home.
"We called the London number using a different mobile phone to examine how the service operated."
Mr Ward said a message told them to put the phone down if they were under 18.
They ended the call, but made another call from the landline to see if the number was obtainable from any phone. They again heard the message and ended the call.
Mr Ward added: "The following day, to my amazement, an operator calling from TBS called on the mobile we had used the previous night - when we had not entered the service proper.
"The woman asked me for my name and address for billing purposes in relation to the few seconds I had registered," he added.
Mr Ward said they then contacted the family on the land line they had used to verify the number, again asking for billing details.
Mr Ward said that each time he had refused to give them details.
Mr Ward said he had contacted phone watchdog ICSTIS about the service, but due to the way the company operates, it was powerless to intervene.
Mr Ward said: "We are seeking advice about the call our son made. He and ourselves may not be liable to pay as the call was made by a minor.
"With regards to the other two calls, TBS can forget it."
Mr Ward said: "Because our son obtained the number from a friend the number will be available to hundreds - if not thousands - of kids in Huddersfield and throughout the country."
A customer service operator said: "The son made the first call. He should find out what he has to pay."
He added: "People need to make sure what kind of numbers they are calling.
"The bill has to be paid, it's as simple as that. If they don't pay it could be put in the hands of a debt collection agency."


Cape Cod is hook-shaped peninsula of the US state of Massachusetts, is a popular summertime destination. It is characterized by quaint villages, seafood shacks, lighthouses, ponds & bay & ocean beaches. The bulk of land on Cape consists of glacial land forms, formed by terminal moraine and outwash plains. Its historic, maritime character and ample beaches attract heavy tourism during summer months.
This beautiful destination aside from being historic dwelled so much at the back of my mind since time immemorial. My sister always told me stories about their summer trips – with her family tagging along the kids, with friends and their family, sometimes with friends of friends – they went there every year. Practically, it's their second home. Setting foot at the Cape is a dream trip to me.
After much prayers and discernment, I scheduled a US trip to visit my Sister and her family and to offer myself a little consolation. Since the trip fell on summer, the Cape Cod dream was few steps closer. And, it happened since my sister's vacation was scheduled just few weeks before I go back home!
Typical scene on the beach during summer!
Breaks can create waves suitable for surfing!
The Nauset Beach in Orleans is just one of those pristine coast line that are too perfect for summer events – be it sunbathing, swimming, skim boarding or just sitting under beach umbrella and watch the horizons beyond. It was far beyond compare to our beaches, definitely it's clean and free from structures and obstructions. It was naturally maintained.
When we got there, it was already filled with beach-goers we had to find a strategic spot with unobstructed view of the waters. The sun was already scorching and decided not to swim, my sister said the waters too cold for her even it is sunny. Lounging on my beach chair was comfortable enough. The sunny skies and blue waters were nothing different back home, I was wondering what was beyond the surface. At a distance, we saw a head or two of seals bobbing up the surface, its either getting away from predators or looking for prey in shallower waters. Few sea gulls flew over humans perhaps looking for food scraps while few also flew over the waters perhaps eyeing for fish.
Pristine and so enticing for swimming or surfing!
Newcomb Hollow Beach is located at northernmost of Wellfleet, it featured a scenic stretch of ocean beach backed with stretch of sand dunes. It is pristine just like other beaches in the Cape and its blue waters were truly inviting not only for swimming but also for surfing as there are bars for waves breaks commonly for short boards.
It was in Fourth of July when we visited Duck Harbor Beach, still in Wellfleet. You need to pass along a stretch of sand dunes, thankfully the parking was free though you need to be early before it gets full. It was dusk and we were in for a glorious display of colors of sunset, the sky was clear and we could saw faint image of the Pilgrim Tower in Provincetown from the horizon ahead of us. Just when the whole country was celebrating this big day we were out there walking along the shore and later sitting in our beach chairs watching the changing hues before us. It was just relaxing!


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Loris Williams (1949-2005)
10 Jul 2018 July 10, 2018 | Tania Schafer
Loris William (2004)
Loris Williams was friend of mine. She loved the smell of lavender, her family and was a proud Aboriginal woman with Mulinjali (Beaudesert – father Cyril Williams) and Birra Gubba (North Qld – mother Agnes Bell) heritage.
I met her when she started working at the State Library of Queensland in 1994. She was the reason I became an Aboriginal librarian and archivist.
Today I want to pay tribute to her and other Aboriginal and Torres Strait Islander women who have lead the way. Because of her, I could …
Loris William and Tania Schafer (nee Bostock)
She was a unique mentor that put your needs first and took great joy in your success.
She had a lovely writing style and was a passionate advocate for Indigenous people's right to know their histories held in information institutions, such as libraries, archives, historical societies, museums and Aboriginal and Torres Strait Islander organistations.
Loris wanted to open Aboriginal and Torres Strait Islander government records, especially at the Queensland State Archives. To accomplish this task Loris became the first Queensland Aboriginal qualified Archivist in 2004. Unfortunately a short-lived dream as in August 2005 Loris died at the age of 55.
Loris and I created the 1996 Aboriginal and Torres Strait Islander Employment and Career Development five year plan at the State Library of Queensland. Loris informed me that through gaining professional qualifications and developing information management skills we would be better candidates for career opportunities. We would be able to influence our fellow librarians or archivists to support new and innovative Indigenous initiatives and break down the barriers in accessing Indigenous content.
Loris always spoke of the need to have qualified Indigenous staff in the archives and record keeping sector. In a paper at the Australian Society of Archivists (ASA) 1999 Conference, she commented "The ASA is to be commended for their commitment to encouraging Indigenous employment by aligning with the Australian Library and Information Association (ALIA) in the Indigenous Recruitment & Career Development Strategy".
She wanted to lead by example, to show Aboriginal and Torres Strait Islander people that a career in the libraries and archives was a way help Australians understand their history, their family lifestyle in a difficult time, and educate future generations on the struggles accomplished by Indigenous people for equality.
Loris Williams during a Cherbourg family history training workshop
Loris joined the team of Queensland Department of Aboriginal and Torres Strait Islander Policies in Community and Personal Histories in 1998 to gain an understanding of records and client service needs and to visit communities, such as Cherbourg (above), to help Aborigines learn their family histories.
As testament to her own personal commitment and lasting legacy, it was due to Loris's leadership, as Convenor of the Indigenous Issues Special Interest Group (IISIG) of the ASA from September 2003 to 2005, that the group produced the brochure 'Pathways to your future and our past: careers for Indigenous peoples in archives and records' to encourage Indigenous people to train as archivists and records managers. This directly paved the way for an ASA scholarship being offered that now deservedly bears Loris's name.
I was fortunate to be the recipient of this scholarship in 2009.
Loris presence still effects my decisions in my career life even after she has been gone for 13 years.
NAIDOC : www.naidoc.org.au/
Loris Williams Meeting room
http://www.slq.qld.gov.au/services/venues/venues-for-hire/loris-williams-room
Loris Williams Memorial Scholarship Aboriginal and Torres Strait Islander.
https://www.archivists.org.au/learning-publications/loris-williams-memorial-scholarship-indigenous-students
Williams family in Beenleigh, Queensland, 2004
State Library of Queensland John Oxley Library Blog
Loris Williams Annual Memorial Lecture, 21 August 2012
Loris Williams Indigenous Scholarship
Posted in People	| Tagged Aboriginal, Archivist, Birra Gubba; NAIDOC, female, Loris Williams, Mulinjali	Jo Browse John Oxley Library
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Ernest Duncan: Soldier, Solicitor and State High Old Boy

redpajama_set_name: RedPajamaCommonCrawl


All-NEW, easy-to-use, 9-inch fishfinder/chartplotter combines CHIRP Sonar with DownScan Imaging™ technology, a super-bright, LED-backlit color display, built-in GPS antenna and high-definition mapping options.
Combining the benefits of CHIRP Sonar with DownScan Imaging for the best possible view below your boat, the Hook-9 CHIRP fishfinder/chartplotter features today's best sonar solution for greater sensitivity, improved target resolution and superior noise rejection for clearer, easy-to-see bait fish and game fish targets – all on a brilliant widescreen display. This package comes with a 83/200 455/800 transducer and AUS/NZ NAV+ Charts.


text:
Q: Fetch data from external database to WordPress website I am new to WordPress, I have an old website containing a simple database to my diner's menu, I am switching my website to WordPress and I need to use my old database, is their anyway I can use both databases? The one already in WordPress and my own database?

A: You can try something like this or refer to this forum: https://wordpress.org/support/topic/multiple-databases-16/
    function seconddb() {
             global $seconddb;
             $seconddb = new
             wpdb('Username','password','database name','localhost');
    }
    add_action('init','seconddb');

redpajama_set_name: RedPajamaStackExchange


text:
«Tagada Jones» — французький панк-гурт з Ренн, що в Бретань. Музичний стиль гурту серед іншого включає хеві-метал та електро. Наразі гурт складається з Niko (гітара та вокал), Waner (бас), Stef (гітара), Job (ударні). Гурт налічує близько 1800 концертів серед 24 країн.

Історія
Гурт сформовано в Ренн, що в Бретані. Гурт спочатку складався з Niko (вокал та гітара), Pascal (гітара), Pepel (бас), Benoît (ударні). У 1995 Tagada Jones випускає свій перший альбом з однойменною назвою Tagada Jones. Два роки по тому, виходить альбом під назвою «À Grands coups de bombes». У 1998 році гурт публікує свій перший студійний альбом
«Plus de bruit» (Більше шуму). В 1999 році під впливом хардкор-панк виходить брутальний альбом «Virus». Але жоден цей альбом не з'являється на музичних платфоромах.

У 2000 відбувається розкол гурту. Наступного року 2001 виходить їх третій студійний альбом «Manipulé», для підтримки якого гурт їде в турне. У 2003 гурт публікує свій четвертий студійний альбом «L'Envers du décor» (За лаштунками), який включає 13 композицій. У 2004 Tagada Jones публікує збірку The Worst of Tagada Jones, яка складається з "найгірших пісень" гурту.

Дискографія

Студійні альбоми
 1998 «Plus de bruit» (Більше шуму)
 1999 «Virus»
 2001 «Manipulé» (Маніпулювали)
 2003 «L'Envers du décor» (За лаштунками)
 2006 «Le Feu aux poudres» (Вогнепровідний шнур)
 2018 «Les Compteurs à zéro» (Лічильники в нулі)
 2011 «Descente aux enfers» (Сходження до пекла)
 2014 «Dissident» (Дисидент)
 2017 «La Peste et le choléra» (Чума та холера)

Альбоми наживо
 2001 «Manipulé Tour 2001»
 2005 «L'Envers du tour»
 2013 «20 ans d'ombre et de lumière» (20 років тіні та світла)
 2015 «Live Dissident Tour» (Живий дисидент тур)

Сінгли
 2011 «Zéro de conduite»
 2005 «Je suis démocratie»

Інше
 1992 «Mortelle rébellion "les premiers pas"» (Касета)
 1992 «A Grands Coups De Bombes»
 1992 «Split avec Mass Murderers»
 1992 «The Worst of Tagada Jones» (Компіляція)
 1992 «6.6.6» (CD що вийшов з нагоди 1000-ого виступу, 6-альбомів, 6-неопублікованих, 6-реміксів)

Примітки

Посилання

 Офіційний сайт гурту

Панк-рок гурти

redpajama_set_name: RedPajamaWikipedia


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HealthCare.gov sign-ups reach 2.84 million as deadline nears
by Zachary Tracer
(Bloomberg) — Ten days before a key Patient Protection and Affordable Care Act (PPACA) individual major medical coverage enrollment deadline, 2.84 million people have selected 2016 coverage through the HealthCare.gov public exchange enrollment system, officials said today.
During the week that ended Dec. 5, 804,338 people chose plans, according to the Centers for Medicare & Medicaid Services (CMS).
That's the biggest single week of sign-up activity since the HealthCare.gov markets opened Nov. 1.
The U.S. Department of Health and Human Services (HHS), the parent of CMS, uses HealthCare.gov to run PPACA exchange plan enrollment efforts in 38 states.
HHS will add millions of automatic plan renewals to the 2016 enrollment total sometime this month. The final total will also include millions of active plan selectors and people with automatically renewed coverage in California, New York and other states with state-based exchange programs.
Consumers have until Jan. 31 to sign up for 2016 individual major medical coverage without showing they qualify for a special enrollment period (SEP). But, in HealthCare.gov states and many other states, consumers who want to have 2016 major medical coverage in place on Jan. 1 must sign up by Dec. 15.
"We are now seeing a surge of interest as we get closer to the deadline," Andy Slavitt, acting CMS administrator, said today during a conference call with reporters.
See also: HealthCare.gov sign-ups top 1 million after second week
Officials at CMS and HHS have said they hope to have about 10 million people enrolled in individual marketplace plans by the end of 2016. They expect to have 9.1 million people enrolled in exchange coverage at the end of 2015.
See also: Medicare enrollment period slides to an end


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The name port comes from the BSD world where a port refer to software "ported" to another operating system or platform. In our case, the port is simply the definitions for building a package.
build(): the function which contains the recipe if not the standard one.
Listing 1 - "The xfce4-libutil Pkgfile"
contributors="tyrry at nutyx dot org"
The line # Depends on: is used for this purpose. It defines all the needed dependencies for the compilation of the package. Dependencies are separated by a comma, a space or both.


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Justia Dockets & Filings Eleventh Circuit Florida Southern District Continental Group, Inc. v. KW Property Management, LLC et al Filing 91
Continental Group, Inc. v. KW Property Management, LLC et al
ORDER re 88 Oral rulings made at end of hearing; Order denying KW Defendants' Motion for Expedited Discovery. See Order for details. Signed by Judge James I. Cohn on 3/11/2009. (lc1)
UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF FLORIDA CASE NO. 09-60202-CV-COHN THE CONTINENTAL GROUP, INC., Magistrate Judge Seltzer Plaintiff, vs. KW PROPERTY MANAGEMENT, LLC d/b/a KW PROPERTY MANAGEMENT AND CONSULTING, LLC; KW HOLDING ONE, LLC d/b/a KW PROPERTY MANAGEMENT AND CONSULTING, LLC; THE GRAND PRESERVE AT NAPLES LLC d/b/a KW PROPERTY MANAGEMENT AND CONSULTING, LLC; and MARCY KRAVIT, Defendants. _____________________________________________/ OMNIBUS ORDER THIS CAUSE is before the Court upon Plaintiff's Emergency Request for Status Conference [DE 71], Plaintiff's Expedited Application to Allow Disclosure of Discovery Produced to Certain Employees of Plaintiff [DE 52], KW Defendants' Motion to Strike [69], Plaintiff's Motion to Compel Production from Defendant Kravit [DE 54], Plaintiff's Supplement to its Motion to Compel Production from Defendant Kravit [DE 67], Defendant Kravit's Motion for Expedited Discovery [DE 56], Plaintiff's Supplement [DE 66] thereto, Defendants' Motion for Court to Expedite Resolution of Subject Matter Jurisdiction, or in the Alternative, Adjourn hearing on Motion for Preliminary Injunction Pending Resolution of the Motion to Dismiss [DE 78] and Motion to Admit Bretton Pollack pro hac vice [DE 86]. The Court has carefully considered the motions and related filings and has heard the argument of counsel at a hearing held on March 9, 2009. This Order serves to memorialize the oral rulings made by the Court at the end of the hearing. In addition to those rulings, listed below, the Court has considered the KW Defendants' cross-motion for limited discovery [DE 22, � 5], Plaintiff The Continental Group's ("Plaintiff" or "TCG") response [DE 35], Defendants' reply [DE 44], and Plaintiff's sur-reply [DE 49-2]. The KW Defendants seek their own expedited discovery on factual issues regarding Marcy Kravit's authority to use her TCG computer, whether TCG's computer system is a "protected computer" under the Computer Fraud Abuse Act ("CFAA") (Count I), and also whether TCG has a legitimate business interest in enforcing its restrictive covenants with Defendant Kravit (state law claim). A protected computer under the CFAA is one that affects interstate commerce, which Plaintiff asserts means it must access the Internet, which its computer system does, and which it alleges Defendant Kravit must have done to remotely access TCG servers via her laptop. The KW Defendants assert that the computer system only connects TCG offices within the state of Florida and does not affect interstate commerce. As there is no diversity in this case, Defendants argue that if the CFAA claim fails, this Court lacks subject matter jurisdiction. Plaintiff argues that its Verified Complaint at a minimum creates a factual issue at the motion to dismiss stage as to subject matter jurisdiction as the merits of its CFAA claim are inextricably intertwined with the subject matter jurisdiction question, therefore making any discovery request irrelevant for purposes of the preliminary injunction hearing. In its Complaint, Plaintiff alleges that Defendant Kravit, acting individually and as an agent of the KW Defendants, exceeded her authorization to access TCG's 2 protected computer in violation of 18 U.S.C. � 1030(a)(2)�, for which a civil action is provided at 18 U.S.C. �1030(g). A "protected computer" is defined as one affecting interstate or foreign commerce or communication. 18 U.S.C. � 1030(e)(2)(B). This Court concludes that the issues of whether Defendant Kravit exceeded her authority or whether TCG's computer is a "protected computer" under the CFAA are elements of the claim rather than simply jurisdictional facts. Thus, under Garcia v. Copenhaver, 104 F.3d 1256 (11th Cir. 1997), the determination of these intertwined elements of the claim are for a jury to decide,1 rather than the Court on a subject matter jurisdiction attack. Cf. Scarfo v. Ginsburg, 175 F.3d 957, 961 (11th Cir. 1999). Defendants are therefore not entitled to expedited discovery. Plaintiff will have to prove the likelihood of success on the merits of its claim at the preliminary injunction hearing. The Court will analyze whether Plaintiff has met all elements of its claim at that time. Defendants will have the opportunity to cross-examine Plaintiff's witnesses at the hearing on these elements.2 Accordingly, it is ORDERED AND ADJUDGED as follows: 1. Plaintiff's Expedited Application to Allow Disclosure of Discovery Produced to Of course, because Plaintiff is seeking a preliminary injunction, the Court will end up making a preliminary determination of whether Plaintiff has a likelihood of success on the merits of its claims. Defendants' request for discovery regarding the "legitimate business interests" of TCG in its trade secrets relating to the state law breach of contract (restrictive covenant) claim also can be delayed until after the preliminary injunction hearing. As with the CFAA claim, Plaintiff will have to prove all elements of its claims to obtain an injunction, with Defendants able to cross-examine the witnesses in support of those elements. 3 2 1 Certain Employees of Plaintiff [DE 52] is hereby GRANTED as to the five named individuals, but is limited to the TCG confidential information found on all KW computers and servers of any size (thus not including proprietary information of KW that has no bearing on the TCG information); 2. 3. KW Defendants' Motion to Strike [69] Plaintiff's Motion is hereby DENIED; Plaintiff's Motion to Compel Production from Defendant Kravit [DE 54] is hereby GRANT ED, though counsel for KW Defendants shall have until March 17 to review the information (including the I-phone and Blackberry Hybrid Information) for privilege prior to its production to Plaintiff; 4. Going forward, Plaintiff and Defendant Kravit shall continue to be bound by their production agreement, with the opportunity for counsel for all Defendants to review information for privilege prior to the turning over of documents to Plaintiff; 5. Plaintiff's request for access to files and data on the KW Defendants' privilege log or submission of the data for an in camera review is hereby DENIED; 6. Defendant Kravit's Motion for Expedited Discovery [DE 56] is hereby GRANTED in part as to the deposition of Turner Billups, and DENIED in part as to the other requests; 7. KW Defendant's cross-motion for limited discovery [DE 22, � 5] is hereby DENIED; 8. Defendants' Motion for Court to Expedite Resolution of Subject Matter Jurisdiction, or in the Alternative, Adjourn hearing on Motion for Preliminary Injunction Pending Resolution of the Motion to Dismiss [DE 78] is hereby 4 DENIED; 9. 10. Motion to Admit Bretton Pollack pro hac vice [DE 86] is hereby GRANTED; The hearing on the Motion for Preliminary Injunction is continued until Thursday, March 26, 2009 at 9:00am; 11. Plaintiff's reply in support of its Motion for Preliminary Injunction is now due Monday, March 16, 2009. DONE AND ORDERED in Chambers at Fort Lauderdale, Broward County, Florida, on this 11th day of March, 2009. Copies furnished to: counsel of record on CM/ECF 5


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Assistant Professor - Department of Physics
Work type: Instructional Faculty – Tenured/Tenure-Track
Categories: Unit 3 - CFA - California Faculty Association, Tenured/Tenure-Track, Full Time, Faculty - Natural Sciences
California State University, San Bernardino (CSUSB) is located in San Bernardino in the Inland Empire, 60 miles east of Los Angeles and operates a satellite campus in Palm Desert located in Coachella Valley. CSUSB serves approximately 20,000 students, of which 81% are first-generation college students and graduates about 5,000 students annually. As a designated Hispanic Serving Institution, CSUSB reflects the dynamic diversity of the region and has one of the most diverse student populations of any university in the Inland Empire, and the second highest Hispanic enrollment of all public universities in California. CSUSB employs 467 full-time faculty and offers 48 undergraduate, 35 graduate, and one doctoral degree programs and 14 academic programs with national accreditation.
At CSUSB, diversity, equity and inclusion are values central to our mission. We recognize that diversity and inclusion in all its forms are necessary for our institutional success. By fully leveraging our diverse experiences, backgrounds and insights, we inspire innovation, challenge the status quo and create better outcomes for our students and community. As part of CSUSB's commitment to hire, develop and retain a diverse faculty, we offer a variety of networking, mentoring and development programs for our junior faculty. We are committed to building and sustaining a CSUSB community that is supportive and inclusive of all individuals. Qualified applicants with experience in ethnically diverse settings and/or who demonstrate a commitment to serving diverse student populations are strongly encouraged to apply. CSUSB has received the Carnegie Community Engagement Classification, which recognizes CSUSB's ongoing commitment to service-learning, a high-impact practice that combines classroom instruction with meaningful volunteer service and correlates strongly to student success.
The Department of Physics at California State University, San Bernardino invites applications from a diverse group of qualified applicants for an Assistant Professor tenure-track position to begin August 2023. The Department offers B.A. and B.S. degrees in Physics, with minors in astronomy and applied physics, and is currently in the planning stages for an interdisciplinary M.S. degree in Materials Science, which is associated with the Center for Advanced Functional Materials (https://www.csusb.edu/center-advanced-functional-materials). We welcome applications in all areas of research in physics. Preference will be given to candidates who are able to teach courses within the full range of undergraduate department courses. The successful candidate will join an intellectually stimulating and innovative academic environment that embraces diversity. We are particularly interested in receiving applications from all groups historically underrepresented in Physics and STEM fields, including intersections across multiple groups.
TYPICAL ACTIVITIES
The successful candidate will teach undergraduate courses in Physics, maintain a robust and ongoing research agenda, and mentor students at the undergraduate level. Candidates will be expected to maintain an active research program appropriate for an undergraduate institution that affords research opportunities for students. The candidate will also advise students and perform career related service roles on and off campus for the department, college, university and professional societies. Furthermore, the candidate will also lead activities that will advance scholarly excellence in Physics. The successful candidate will be expected to meet the traditional requirements of excellence in teaching, active scholarly and professional work, and service to the University and community.
Qualified candidates must demonstrate a commitment to excellence in teaching and mentoring a diverse student population and to working effectively with faculty, staff and students across a wide range of disciplines.
Candidates are required to have a Ph.D. in Physics or an equivalent degree in a closely related area by time of appointment. However, candidates with "all but dissertation" (ABD) are considered as long as expected to complete the Ph.D. by the time of the appointment. We welcome applications from all areas of research in Physics.
Preference will be given to candidates who have experience teaching and conducting research with undergraduate students and could teach a broad spectrum of undergraduate physics courses and in our upcoming Material Science MS program.
The person holding this position is considered a 'mandated reporter' under the California Child Abuse and Neglect Reporting Act and is required to comply with the requirements set forth in CSU Executive Order 1083 as a condition of employment.
Following a conditional offer of employment, a background check (including a criminal records check) must be completed satisfactorily before any candidate may start work with CSUSB. Failure to satisfactorily complete the background check may result in the withdrawal of the offer of employment. Note: CSUSB cannot deny an applicant a position solely or in part due to a criminal conviction history until it has performed an individualized assessment and linked the relevant conviction history with specific job duties in the position being sought.
Please note: Current employees who are offered positions on campus will be required to undergo a background check for any position where a background check is required by law or that CSUSB has designated as sensitive. Sensitive positions are those requiring heightened scrutiny of individuals holding the position based on potential for harm to children, concerns for the safety and security of people, animals, or property, or heightened risk of financial loss to CSUSB or individuals in the university community.
For health and well-being, CSUSB is a smoke & tobacco-free campus. The university is committed to promoting a healthy environment for all members of our community.
The Department of Physics currently offers B.A. and B.S. degrees in Physics, with minors in astronomy and applied physics, and is in the planning stages for an interdisciplinary M.S. degree in Materials Science, which is associated with the NSF CREST-funded Center for Advanced Functional Materials (https://www.csusb.edu/center-advanced-functional-materials).
Our faculty are actively involved in research and in professional organizations in their respective fields. Faculty have been successful in obtaining grants through the funding organizations such as NSF and NASA, in particular for multi-million-dollar, interdisciplinary programs both with faculty at CSUSB and external collaborators. Faculty members utilize and are engaged in understanding best practices in physics education. We have approximately 100 majors,9 tenure-line faculty, and 9 lecturers, with a gender balance among both tenure-line and lecturer faculty members.
Our department ranked number three in the number of physics degrees granted to underrepresented minority students at bachelor's institutions and number ten in physics degrees granted to Hispanic students among all institutions nationally. A significant number of students participate in research with CSUSB faculty. The department is actively involved in and a strong supporter of the Cal-Bridge program (https://www.calbridge.org) and a current PhysTEC grantee. CSUSB physics alums have successfully transitioned to graduate school at institutions such as Arizona, Maryland, UCLA, UCSB, UCI, UCM, and/or been hired at companies such as Tokyo Electron, Lockheed Martin, NASA Armstrong, Naval Surface Warfare Center, Kelly Space, Millennium Space Systems/Boeing, and local school districts. Multiple alumni in recent years have been awarded NSF Graduate Research Fellowships.
To find out more about the Department of Physics visit our website: https://www.csusb.edu/physics
For more information regarding the position, please contact:
Recruitment Chair
Dr. Sara Callori
sara.callori@csusb.edu
Please submit
Cover Letter that includes the following three (3) separate statements regarding your preparation for the position. The hiring committee will be conducting an initial blind review of applications; therefore, applicants should avoid including any identifying information (names, affiliations, gendered language, etc.) in these statements:
A Teaching Statement that details your teaching philosophies and how to promote learning in diverse student populations. We request that applicants address how they would promote our Physics Program Learning Outcomes 2 and 3 in their teaching. (https://www.csusb.edu/physics/degrees-and-certificates/program-learning-outcomes)
A Research Statement that details your research, professional accomplishments, and future plans at CSUSB. Include sustainability of research endeavors at CSUSB and how undergraduates would be involved in a meaningful way.
If available, evidence of teaching effectiveness such as teaching portfolios, reports on teaching observations, and/or student evaluations of teaching.
Unofficial copies of all postsecondary degree transcripts (official transcripts will be required prior to appointment).
Reference List - names, telephone numbers, and email addresses of three (3) referees whom we may contact to obtain letters of recommendation.
Confidential letters of recommendation may be solicited from those listed as references on the application if the applicant is moved forward in the recruitment process. Non-confidential letters of recommendation can be uploaded by the applicant during the application process.
Diversity Statement, which may include your interpretation of diversity, equity and inclusion, and must include specific examples of how your background and your educational and/or professional experiences have prepared you for this role at California State University, San Bernardino (maximum 1,000 words).
Formal review of applications will begin November 1, 2022 and continue until the position is filled.
If you are interested in this opportunity, we invite you to apply by using this CSU Recruit hyperlink at:
https://secure.dc4.pageuppeople.com/apply/873/gateway/Default.aspx?c=apply&sJobIDs=517478&SourceTypeID=803&sLanguage=en-us&lApplicationSubSourceID=11243
Salary is commensurate with experience.
CSU Salary Schedule: https://www.calstate.edu/csu-system/careers/compensation/Pages/salary-schedule.aspx
A background check (including a criminal records check) must be completed satisfactorily before any candidate can be offered a position with the CSU. Failure to satisfactorily complete the background check may affect the application status of applicants or continued employment of current CSU employees who apply for the position.
California State University, San Bernardino is an Affirmative Action/Equal Opportunity Employer. We consider qualified applicants for employment without regard to race, religion, color, national origin, ancestry, age, sex, gender, gender identity, gender expression, sexual orientation, genetic information, medical condition, disability, marital status, or protected veteran status. This position adheres to CSU policies against Sex Discrimination, Sexual Harassment, and Sexual Violence, including Domestic Violence, Dating Violence, and Stalking. This requires completion of Sexual Violence Prevention Training within 6 months of assuming employment and on a two-year basis thereafter. (Executive Order 1096)
This position may be "Designated" under California State University's Conflict of Interest Code. This would require the filing of a Statement of Economic Interest on an annual basis and the completion of training within 6 months of assuming office and every 2 years thereafter. Visit the Human Resources Conflict of Interest webpage link for additional information:
https://www.csusb.edu/human-resources/current-employees/employee-relations/conflict-interest
Advertised: 09 Aug 2022 Pacific Daylight Time
Applications close:
Assistant Professor - Department of Physics San Bernardino - San Bernardino Campus
Instructional Faculty – Tenured/Tenure-Track 1
Tenured/Tenure-Track 1
Unit 3 - CFA - California Faculty Association 1
Faculty - Natural Sciences 1


Banks Tempt Underwater Home Owners with Cash — Would You Take It?
A short sale might be worth more than avoiding a foreclosure on your credit report. For some, it means cold hard cash.
If your lender offered you as much as five figures to move out of your home because you couldn't make your mortgage payment, would you do it or wait for the lender to foreclose?
The answer would seem to be a resounding "hell, yes." But many people sit tight.
When Bank of America offered short-sale incentives of $5,000 to $20,000 to 20,000 Florida home owners late last year, only 3,000 home owners expressed an interest in participating.
One reason? Folks can often live rent-free while the foreclosure process winds its way through the red tape.
But, a cash "bonus" paired with a short sale that lets you avoid a foreclosure on your credit history can be a sweet deal.
An incentive payment might be as little as $3,000 via the federal government's Home Affordable Foreclosure Alternatives program. But private lender programs offer 10 times that much, depending on where you live, which short sale program you use, and which company holds your mortgage, says BusinessWeek.
"Banks are nudging potential sellers by pre-approving deals, streamlining the closing process, forgoing their right to pursue unpaid debt, and in some cases providing large cash incentives," Moody's Senior Credit Officer Bill Fricke told the magazine.
1. Help the bank sell your home. In a short sale, you find someone willing to buy your home for less than what you owe on the mortgage and your lender agrees to take the sale price.
2. Move on without a fight.
3. Probably live in a state where it takes years, rather than months, for the bank to foreclose. In those areas, it's cheaper for the bank to pay you to do a short sale than to pay the cost of a multi-year-long foreclosure.
1. Make sure the lender can't come after you later to collect any shortfall between what you owe on the mortgage and what you're selling your home for. Some, but not all, states prohibit that.
2. Talk to an attorney and a tax adviser so you know what will happen financially after the short sale. If you sell now through the end of 2012, the tax rules for short sales say you won't owe any income tax on $1 million (singles) to $2 million in forgiven mortgage debt (married couples). Those tax rules, part of the Mortgage Forgiveness Debt Relief Act, expire at the end of this year and only apply to your primary residence.
3. Hire a REALTOR® experienced in short sales to handle the transaction. Look for an agent who's earned the SFR (short sales and foreclosure resource) designation.
4. Figure out where you're going to move and sign a lease now because your credit score will likely drop if you stop paying your mortgage and short sell your home. A low credit score can make it difficult to get a rental home.
By the way, you can ask your bank if it's willing to work with you on a short sale, but asking for an incentive too? That's not how it works. Banks choose you for an incentive program, and how they decide isn't clear, though they're less likely to offer cash in states where it only takes a couple of months to foreclose.
So would you take the cash and short sale, or hold out?


text:
'The Voice' Top 24: How to vote for your favorite artist of Season 16
Paul Sheehan
Trae Patton/NBC
Show support for your favorite artist in the Top 24 of "The Voice" by casting a vote for them during the live show on Monday, April 29. Each of the two dozen hopefuls will get a chance to sing a solo, albeit a brief one, during the two-hour show. You can cast up to 10 votes per artist in one of three ways: on the official App, which is available for download on the Apple App Store and Google Play; on the official website page of "The Voice" ; and by streaming their songs on Apple Music.
On Tuesday's results show, Carson Daly will reveal the eight top vote-getters who will advance to the Top 13, regardless of which team they are on. Then each of the four coaches — Kelly Clarkson, John Legend, Adam Levine and Blake Shelton — will get to save one of their remaining artists.
The final contestant will be determined by a live battle with Kanard Thomas, the winner of "The Comeback Stage." He will face off against a contestant who was eliminated during the Cross Battles. Each will be vying for the Twitter Save that will make them the lucky 13th artist still vying to win season 16.
SEE 'The Voice' Top 24 preview: What songs will the artists perform live on Monday April 29?
Which coach do you think has the strongest team at this stage of the season 16 competition? Vote in our poll below and then be sure to sound off on your most (and least) favorite coach and artist in the comments section.
SIGN UP for Gold Derby's newsletter with experts' latest predictions


Excitation-contraction coupling involves the faithful conversion of electrical stimuli to mechanical shortening in striated muscle cells, enabled by the ubiquitous second messenger, calcium. Crucial to this process are ryanodine receptors (RyRs), the sentinels of massive intracellular calcium stores contained within the sarcoplasmic reticulum. In response to sarcolemmal depolarization, RyRs release calcium into the cytosol, facilitating mobilization of the myofilaments and enabling cell contraction. In order for the cells to relax, calcium must be rapidly resequestered or extruded from the cytosol. The sustainability of this cycle is crucially dependent upon precise regulation of RyRs by numerous cytosolic metabolites and by proteins within the lumen of the sarcoplasmic reticulum and those directly associated with the receptors in a macromolecular complex. In addition to providing the majority of the calcium necessary for contraction of cardiac and skeletal muscle, RyRs act as molecular switchboards that integrate a multitude of cytosolic signals such as dynamic and steady calcium fluctuations, β-adrenergic stimulation (phosphorylation), nitrosylation and metabolic states, and transduce these signals to the channel pore to release appropriate amounts of calcium. Indeed, dysregulation of calcium release via RyRs is associated with life-threatening diseases in both skeletal and cardiac muscle. In this paper, we briefly review some of the most outstanding structural and functional attributes of RyRs and their mechanism of regulation. Further, we address pathogenic RyR dysfunction implicated in cardiovascular disease and skeletal myopathies.
In striated and smooth muscle cells, fluctuations in the intracellular levels of Ca2+ ions greatly determine the magnitude and duration of contractile force. In cardiac and skeletal muscle, depolarization of the external membrane and its invaginations, the T-tubules, elicits swift and massive Ca2+ release from the sarcoplasmic reticulum (SR), which in turn causes 'flooding' of the contractile myofilaments with Ca2+ and induction of contraction. This exquisitely coordinated series of events, in which an electrical stimulus (depolarization) is converted into a mechanical contraction, is collectively termed 'excitation-contraction (EC) coupling', and it has as central players the voltage-dependent Ca2+ channels/dihydropyridine receptors (DHPRs) as the sarcolemmal voltage sensors, and the Ca2+ release channels/ryanodine receptors (RyRs) as the SR Ca2+ release conduits. The structural and functional communication between the voltage sensor and the RyR dictate the magnitude of Ca2+ release from the SR, and thus the force of contraction. In fact, genetic mutations in either of these two proteins, or alterations in the environment that promotes their functional coupling, are known to cause ventricular arrhythmias, hypercontractures and/or pathological remodeling of cellular structures. Excellent reviews on DHPRs have appeared recently [1, 2]. In the current review, we focus on RyRs to discuss their most prominent structural and functional attributes, and to suggest mechanisms by which their dysfunction leads to disease.
RyRs are not restricted to striated muscle. This class of intracellular Ca2+ release channels is also found in the endoplasmic reticulum of neurons, exocrine cells, smooth-muscle cells, epithelial cells, lymphocytes, sea-urchin eggs, and many others . In all of these cells, RyRs play a central role in the regulation of the intracellular free Ca2+ concentration ([Ca2+]i), whose elevation triggers a cascade of events that culminates in, for example, neurotransmitter release, hormone secretion, lymphocyte activation and egg fertilization. To gain the functional flexibility necessary to respond to different triggering signals, at least three isoforms of RyRs are expressed in mammals, each one encoded by a distinct gene (ryr1, ryr2 and ryr3), residing on separate chromosomes. RyR1 is expressed predominantly in fast- and slow-twitch skeletal muscle and at lower densities in cerebellar Purkinje cells, gastric smooth muscle and B lymphocytes, among others. RyR2 was originally purified from cardiac muscle (it is the major isoform expressed there), but is also robustly expressed in neurons, and in visceral and arterial smooth muscle. RyR3 is the least understood of the RyR isoforms and seems to play its most important role during development, although in mature cells RyR3 is found in diaphragm, epithelial cells, brain, and smooth muscle [3, 4]. There is approximately 65% amino acid sequence identity between mammalian RyR isoforms . Most prominent in sequence variation are three regions of divergence, termed D1, D2 and D3, corresponding to amino acids 4254 to 4631, 1342 to 1403, and 1872 to 1923 in RyR1, respectively to amino acids 4210 to 4562, 1353 to 1397, and 1852 to 1890 in RyR2, respectively. Because RyR2 cannot rescue EC coupling in dyspedic myoblasts (immature muscle cells lacking RyR1) , it is likely that these regions of divergence are responsible for the incapacity of rescuing EC coupling with either isoform. Indeed, D2 has been shown to play a crucial role in establishing mechanical coupling between RyR1 and the skeletal DHPR (Cav1.1) , but a complete picture of all the structural elements participating in this mode of EC coupling is still lacking. D3, by contrast, contains a low-affinity Ca2+ binding site , but whether this site corresponds to a Ca2+ inactivation site that operates in vivo has not been determined.
With a molecular weight in excess of 2 MDa, RyRs are indisputably the largest known ion channels. Although structural study of RyRs has been challenging because of the channel's large size, some details of RyR structure have been obtained through cry-oelectron microscopy (cryo-EM) [9–13], comparative modeling  and recently, x-ray crystallography of small RyR segments [15–17]. In electron micrographs, purified RyRs are seen as quatrefoil or cloverleaf-shaped structures [18–20], or in volume-filled renderings as mushroom-shaped structures, with a large (27 × 27 × 12 nm) cytoplasmic assembly and a smaller transmembrane 'stalk' spanning approximately 6.5 nm from the base of the cytoplasmic region and extending into the SR lumen . The quatrefoil structure results from the symmetrical arrangement of four identical subunits of approximately 5,000 amino acids each, thus a single tetrameric channel encompasses approximately 20,000 amino acids. As if this structural assemblage was not massive enough, an RyR in situ serves as a structural scaffold for other proteins and cofactors that add to its discrete bulkiness and distinctive shape. Indeed, RyRs and associated proteins where first observed as the 'foot' structures that bridge the gap of approximately 12 nm that separates T-tubule and SR membranes in cardiac and skeletal muscle .
The cytoplasmic assembly of RyRs consists of 15 distinct domains per subunit, including clamp-shaped domains around the periphery of the channel, connected to 'handle' domains surrounding a central cavity [23, 24]. Single-particle reconstruction studies indicate that moving between the closed and open states involves conformational changes in the cytoplasmic assembly and in the transmembrane domains, which undergo dilation and constriction around the pore, similar to the iris of a camera diaphragm . Molecular sieving experiments, streaming potential experiments, and electrical distance measurements have suggested a pore approximately 3 Å wide, with a voltage drop of approximately 10.4 Å in length . RyR mapping indicates that the pore of the channel consists of six to eight transmembrane segments . Recent studies using single-particle three-dimensional reconstructions of cryo-EM images of RYR1 at refined resolutions (approximately 10 Å) have enabled a more detailed picture of the secondary structure of the channel pore to be pieced together. Samso et al. suggested that each monomer has at least six transmembrane α-helices, with four inner helices forming a 'tepee' around the central cavity. Further, in the closed state of the channel, the conformation of the inner helices of RyR1 resembles that of the closed KcsA channel. However, Ludtke et al. identified only five helix-like densities lining the pore of the RyR1 channel, which, in its closed state, more closely resembles the structure of open MthK channels rather than closed KcsA channels. The authors conceded that higher resolution was needed for further clarification.
This incongruity was addressed in a later paper , in which the authors compared the open and closed conformation of the channel to produce three independent 3D reconstructions, all of which upheld the previous report of six transmembrane helices. Those authors found that relocation of the ion pathway, in which the inner helices bend outward and the inner branches separate slightly, is directly related to an increase of 4 Å in diameter of the pore during channel gating. Further, by superimposing the 3D reconstructions of the open and closed channel, they were able to identify structural hinges that correspond to the previously identified binding sites of regulatory proteins, including calmodulin (CaM) and FK506 (tacrolimus)-binding protein (FKBP)12. Thus, they suggested that the hinges may be the mechanism by which the binding of a small effector is transduced to the pore region.
Two studies have recently solved high-resolution crystal structures (2.5 Å) of portions of the N-terminal region of the skeletal RyR (RyR1) associated with pathogenic mutations. The first study crystallized the N-terminal 210 residues, which were found to adopt a β-trefoil fold, similar to a suppressor domain of inositol trisphosphate receptors (IP3Rs) . The disease mutations investigated in this study clustered in a region within a newly identified domain, highlighting its importance in channel regulation. The authors proposed that the β-trefoil fold, like the analogous structure in IP3Rs, may couple to the C-terminal channel domain to form a suppressor/coupling domain. The second study crystallized a larger construct, comprising N-terminal residues 1 to 559 . This region folds into three distinct domains (arbitrarily termed A, B and C) per monomer (Figure 1), forming a vestibule around the pore of the channel. Fifty pathogenic RyR mutations have been mapped to this region, grouped on the basis of their proposed effect on channel function. Six of the mutations are buried deep within the domains, most probably causing protein misfolding rather than faulty interaction with channel modulators. Significantly, most mutations were mapped to inter-domain and inter-subunit interfaces, thus suggesting that RyR gating is allosterically coupled to the movement of the A, B and C domains, and agreeing well with the hypothesis proposed by Ikemoto et al.[29–31] that disruption of any of the inter-domain interfaces by disease-associated mutations may destabilize closed states, increasing the probability of the channel opening.
Crystallized structure of rabbit ryanodine receptor (RyR)1 for amino acid residues 1-559. This RyR1 segment folds into three distinct domains, forming a vestibule around the four-fold symmetry axis: domain A (blue; 1-205), domain B (green; 206-394) and domain C (red; 395-532). (A) Cytoplasmic view; (B) close-up lateral view from the four-fold symmetry axis, (C) Docking of domain A alone (blue) or domain BC alone (red) yields a near-perfect superposition on the docking position for ABC (grey). Adapted from Tung, et al. .
As mentioned above, RyRs are often complexed with several accessory proteins, forming an intricate multi-protein array [32, 33]. The best known RyR-interacting proteins are CaM, which tonically inhibits RyR2 activity and produces biphasic effects on RyR1 [34, 35]; FKBP12 and FKBP12.6, which stabilize RyR1 and RyR2 closures [36–38]; and the ternary complex triadin-junctin-calsequestrin, which 'senses' luminal Ca2+ content and modulates RyR activity by acting either as a Ca2+ reservoir or as a direct channel ligand [39–47]. More recently, RyR2 has been found to hold anchoring sites for protein kinase (PK)A, protein phosphatase (PP)1, the cAMP-specific phosphodiesterase (PDE)4D3 and Ca2+/calmodulin-dependent protein kinase (CaMK)II [37, 48], emphasizing the importance of RyR2 regulation by phosphorylation . In cardiac cells, sorcin exerts protein-protein interactions with the RyR and inhibits Ca2+ release in a Ca2+-dependent manner [49, 50].
The binding sites of several regulatory proteins have been mapped near the 'clamp' region of the channels, encompassing subdomains 5 to 10, an apparent hot-spot for allosteric modulation. Phosphorylation sites for CaMKII and PKA, including Ser2808 and Ser2030, occur in different subdomains within this region [51, 52]. Muscular A kinase anchoring protein (mAKAP) is believed to bind to RyRs via leucine zippers at residues 3003 to 3039, tethering PKA close to these phosphorylation sites . Another scaffolding protein, Homer, purportedly interacts with RyRs via the clamp domain, where it brings Ca2+ signaling proteins in close proximity to their respective binding sites, and may facilitate crosstalk between RyRs and proteins in the surface membrane, such as DHPRs and β-adrenergic receptors [53–55].
CaM, both in its Ca2+-bound (Ca2+-CaM) and unbound forms (apoCaM), reportedly binds in a cleft between the 'clamp' and 'handle' regions . This cleft occurs between domains 3 and 7 on a portion of the cytoplasmic assembly of the channel facing the SR, about 10 nm from the pore . From their cryo-EM studies, Samso and Wagenknecht [57, 58] proposed a model in which CaM transitions between a distinct, but overlapping apoCaM site as calcium concentration ([Ca2+]i) fluctuates. According to this model, as apoCaM binds Ca2+ ions, it loses affinity for the apoCaM site and translocates to the nearby Ca2+-CaM site. The CaM binding sites identified by these studies was corroborated by a Förster resonance energy transfer (FRET)-based approach, which identified a CaM target helix that spanned residues 3614 to 3643. However, [Ca2+]-dependent translocation of CaM between adjacent or overlapping sites could not be detected by FRET, indicating that any such movements must be subtle. The authors pointed out that such structural rearrangements could also be explained by changes in the interaction of CaM with the RyR target sequence or by rotation of CaM around its major axis .
Collins originally reported that a 12-kDa immunophilin (FKBP12) copurified with RyR1 . Jayaraman et al. later reported that FKBP12.0 binds to RyR1 with a stoichiometry of one molecule per tetrameric channel . Experimental techniques similar to those described above have shown that the binding site of FKBP12 also occurs in the clamp region of the channels; however, there is some controversy about the exact amino acid region(s) responsible for this interaction. For RyR1 and RyR3, a valyl-prolyl motif (amino acid residues 2461 and 2462 in RyR1) seems to berequired for binding of FKBP12/FKBP12.6 [62, 63]. For RyR2, a variant of this motif (isoleucyl-prolyl sequence 2427 and 2428, respectively) has been implicated in binding FKBP12.6 . However, Masumiya et al. reported that mutation of Ile-2427 or Pro-2428 does not alter FKBP12.6 binding , and further, that the RyR2 polypeptide fragment encompassing residues 1 to 1855 is sufficient for binding of FKBP12.6 . Zhang et al. also found that other regions of RyR2 contribute to FKBP12.6 binding . As with CaM, Wagenknecht and colleagues  used 3D reconstructions of cryo-EM images of purified RyRs complexed with FKBP12 to investigate the site of the interaction, which was identified on the opposite side of domain 3 from CaM, about 12 nm from the pore. A later study compared 3D reconstructions of native and FKBP12-stripped RyR1, identifying two surfaces of interaction between FKBP12 and RyR1: a portion of the β-sheet of FKBP12 interacts with domain 9 of RyR1 and the intersection of domains 3, 5 and 9, while loop 87 to 90 interacts with domain 3 of RyR1 .
In cardiac muscle, a small influx of external Ca2+ (ICa) through DHPRs (Cav2.1) binds to and opens RyR2, releasing a larger amount of Ca2+ from the SR. This process, known as Ca2+-induced Ca2+ release (CICR [67, 68]), occurs in diads, which are specialized regions in which a segment of a T-tubule seems to be continuous with a semi-spherical extension of the SR . CICR amplifies the incoming Ca2+ signal approximately 10 to 20 times, and is therefore the major component of the intracellular Ca2+ transient that induces contraction. In skeletal muscle, ICa is not required for contraction . Instead, mechanical coupling between DHPRs (Cav1.1) and RyR1 (direct or facilitated by intermediary proteins) triggers Ca2+ release from the SR immediately after sarcolemmal depolarization [70, 71]. At the triads, where a segment of one T-tubule seems to be continuous with two SR evaginations, not all RyRs are closely apposed to DHPRs; nearly half of RyRs remain DHPR-free and are therefore presumed to be activated by Ca2+ release from neighboring RyRs, effectively amplifying the Ca2+ signal . Thus, common subcellular structures participate in EC coupling, but different processes link membrane depolarization to Ca2+ release in cardiac and skeletal muscle. In this section, we review some of the most prominent regulators of RyR1 and RyR2 and their effect in Ca2+ release in skeletal and cardiac muscle.
All three RyR isoforms harbor both activating and inactivating Ca2+ binding sites. Regardless of some differences (noted below), the Ca2+ affinity for those sites is roughly similar for all RyRs. Thus, Ca2+ plays a crucial role in the modulation of RyR activity, even in skeletal muscle .
The RyR is a Ca2+-gated channel, hence, functional assays that measure its activity ([3H]ryanodine binding, reconstitution in lipid bilayers, Ca2+ sparks) require a critical [Ca2+] in the medium to maintain the channel in its open state. However, despite the fact that RyRs in situ normally encounter fast and transient changes in [Ca2+], most of the functional characterizations of single RyR have been obtained under the continuous presence of a critical [Ca2+], that is, under steady-state conditions. How similar is this characterization to that obtained under a transient application of [Ca2+]? Fabiato, in his classic studies delineating CICR [67, 68], found that the amount of Ca2+ release was strongly dependent on the velocity of the Ca2+ pulse ((d[Ca2+]/d t) applied to skinned cardiac fibers. In light of these data, it is surprising that few studies have addressed the importance of dynamic fluctuations of Ca2+ on RyR kinetics. Three such studies have revealed that a fast Ca2+ stimulus elicits only a transient increase in the Po of RyRs; however, if Ca2+ is applied rapidly but sustained for long periods, RyR Po will 'relax' to a new steady-state that follows a bell-shaped curve as a function of the magnitude of Ca2+ stimulus. Thus, Po-[Ca2+] curves of greater magnitude emerge from titration of RyR activity with fast, calibrated Ca2+ pulses than those obtained under similar but steady applications of Ca2+ (Figure 2) [73–75]. The implication of these findings is that there are components of RyR activity that remain undetected in most of the assays presently used, and these aspects of RyR regulation may explain seemingly discrepant results, as in the case of RyR phosphorylation (see below).
Modulation of ryanodine receptors (RyRs) by Ca 2+ . (A) Ensemble currents of single RyR2 show the effect of fast Ca2+ pulses on the Po of a non-phosphorylated channel ('control') or the same channel after phosphorylation with the catalytic subunit of protein kinase A ('+PKA'). Laser photolysis of 'caged Ca2+' (o-nitrophenyl EGTA, tetrapotassium salt; NP-EGTA) increased [Ca2+] from 0.1 to 10 μmol/l at the point labeled as 'Ca2+ pulse' (modified from . (B) Ca2+-Po curves of RyR1 and RyR2. Channel activity was measured at the indicated stationary concentrations of Ca2+ ('RyR1' and 'RyR2 steady-state') and right after a fast Ca2+ pulse, as in (A) ('RyR2 (peak Po)') (unpublished results) (see text for details).
Under steady-state conditions, Ca2+ concentrations in the range of approximately 100 nmol/l to approximately 10 μm/l activate all three RyR isoforms [76–78]. The activation curve is sigmoidal, but the exact Hill number (cooperativity) and the plateau (maximal activation) depend greatly on the presence of other cytosolic ligands. Higher concentrations of Ca2+ in the range of 100 μmol/l to approximately 10 mmol/l also inactivate the three RyR isoforms, although there is considerable RyR heterogeneity in this process [79, 80]. In general, Ca2+-dependent inactivation is most prominent in RyR1 and less important in RyR2 and RyR3 . In fact, complete Ca2+-dependent inactivation in isolated RyR2 channels occurs at such high [Ca2+] (>10 mmol/l) that its physiological relevance is questionable [58, 76]. The agonist effect of ATP and the inhibitory action of Mg2+ greatly influence the kinetics of calcium-dependent activation and inactivation , but the concentration of these two ligands is not expected to change dramatically over a short period or on a beat-to-beat basis, thus they may be considered rather as tonic modulators of RyRs whose influence becomes relevant under periods of intense muscle activity or in precarious metabolic states. Given the greater sensitivity of RyR1 to Ca2+-dependent inactivation, it is not surprising that Mg2+ also exerts a more powerful inhibition on the RyR1 isoform [74, 81], with Mg2+ apparently binding to both Ca2+ activation and inactivation sites, attenuating the former and intensifying the latter.
Recently, regulation of RyRs by luminal (intra-SR) Ca2+ has been proposed as a critical control mechanism of Ca2+ release, especially in cardiac cells. The crucial observation is that, beyond a certain threshold, small changes in SR Ca2+ load result in far greater increases in Ca2+ release, with the relationship described as an inverse hyperbole with high degree of cooperativity [82, 83]. Direct Ca2+ binding to sites available only from inside the SR , activation of cytosolic sites by the Ca2+ ions being permeated by the channel ('feed-through' mechanism ), and most notably, regulation by the junctin-triadin-calsequestrin ternary complex (for example, [39–47]) remain as the leading candidate mechanisms effecting luminal Ca2+ regulation of RyRs, although it has been difficult to dissect out the specific contribution of each of these phenomena.
RyRs are structural scaffolds for important kinases and phosphatases , and in the heart, RyR2 is one of the first proteins to undergo phosphorylation during β-adrenergic stimulation [86–88]. However, the functional effect of RyR phosphorylation is unclear and remains the subject of intense debate. All potential functional outcomes have been attributed to RyR phosphorylation. On one hand, Li et al. found that PKA phosphorylation of RyR2 has little functional relevance for diastolic Ca2+ release if SR Ca2+ levels remain constant. On the other hand, other groups have suggested that PKA phosphorylation of RyR2 is so essential to intracellular Ca2+ homeostasis that derangement of this process may be the basis for heart failure (HF) [37, 90] and catecholaminergic polymorphic ventricular tachycardia (CPVT) episodes . Between these two extremes, other results, mainly from in vitro experiments, imply that PKA phosphorylation increases [86, 92], decreases [74, 93] or has no effect  on RyR2 activity.
Several factors preclude an easy interpretation of phosphorylation results. First, RyRs contain multiple phosphorylation sites that, depending on their phospho-state, may attenuate or synergize the effect of the other sites, or may require prior phosphorylation to activate the whole protein. To date, three phosphorylation sites have been recognized: Ser2809 (mouse RyR2 nomenclature) was first identified by Witcher et al. as a CaMKII site, and later, Wehrens et al. suggested it as the only PKA site , even though RyR2 from mice with genetic ablation of this site may still be phosphorylated by PKA . Ser2815 and Ser2030 seem to be exclusively phosphorylated by CaMKII  and PKA , respectively. Second, as mentioned above, RyR activity is strongly dependent on the speed of Ca2+ application, which in turn may greatly influence the overall effect of phosphorylation. For example, PKA phosphorylation of isolated RyR2 increases a transient component of activity (peak activation) but accelerates the rate of adaptation to a lower steady-state level of activity [74, 88]. In cellular settings, this effect would translate into greater and faster rates of Ca2+ release in response to a given amount of Ca2+ entry. Elegant experiments in which SR Ca2+ load and ICa were kept constant showed that β-adrenergic stimulation of ventricular myocytes accelerates the rate of Ca2+ release and has little effect on the magnitude of the [Ca2+]i transient . Similarly, experiments in rat and mouse skeletal muscle fibers showed little or no effect of β-adrenergic stimulation on the macroscopic Ca2+ transients . A recent paper suggested that differences in the redox state of RyR could account for some the discrepancies seen . Although appealing, this hypothesis still needs to be corroborated.
CaM regulates RyR activity both directly as a ligand, and indirectly as a cofactor for CaMKII. CaM binding to RyR1 increases channel activity at low [Ca2+], and decreases activity at high [Ca2+] . Nevertheless, at the cellular level, this fine modulation might be negligible compared with the effect of other RyR regulators such as DHPR and calcium . In skeletal muscle cells, CaM is proposed to protect RyR1 from oxidative stress and also work as an oxidative stress sensor (see below). RyR1 nitrosylation decreases CaM binding and increases channel activity . The physiological importance of this mechanism is not clear, but it has been related to pathological processes . In single RyR2 channels, only inhibitory effects by CaM have been shown . CaM binding to both RyR1 and RyR2 can also be regulated by S100A1, a calcium-activated protein that competes with CaM for the RyR binding site [103–105]. Although the physiological beat-to-beat significance of this interaction is not yet clear, its chronic deregulation potentially plays a role in HF [106, 107]. A recent study suggested that PKA phosphorylation decreases CaM binding, which would subsequently increase channel activity .
S-nitroso-N-acetyl penicillamine (SNAP), which targets several EC-coupling proteins, increases inotropy of cardiac myocytes at low concentrations, but decreases it at high concentrations [113, 114]. It has been proposed that reduced glutathione (GSH) could quickly react with and scavenge NO in cardiac cells . Under these circumstances, nitroso-GS or other small nitrosylated molecules would be responsible for RyR oxidation . It is also possible that the close proximity of nitric oxide synthase (NOS)-3, xanthine oxidase and RyR2 in cardiac caveolae creates a microenvironment capable of directly nitrosylating RyR2 , although in physiological conditions the main targets of NOS seem to be other EC-coupling proteins .
In this section, we describe the role of RyR dysfunction in the generation of genetic and acquired diseases afflicting skeletal and cardiac muscle.
Mutations in RYR1, the gene encoding the skeletal isoform of RyRs, are associated with malignant hyperthermia (MH), a pharmacogenetic disease triggered by inhalational anesthetics or depolarizing muscle relaxants [116, 117]. SR Ca2+ 'leak' or excessive Ca2+ mobilization from the SR due to hyperactivity of RyR1 (especially at rest) seems to be the underlying mechanism for this syndrome , although increased resting [Ca2+] in human muscle has yet to be categorically demonstrated . MH episodes are rare (approximately 1 in 10,000 surgeries ), but in their severest clinical presentation, susceptible individuals anesthetized with halothane or other volatile anesthetics suddenly develop muscle rigidity, hyperkalemia, arrhythmias, respiratory and metabolic acidosis, and an alarming increase in body temperature. Fulminant death inexorably follows unless body temperature is lowered and the excessive SR Ca2+ leak is prevented by dantrolene sodium, which presumably blocks RyR1, but not RyR2 . More than 100 different point mutations in human RYR1 have been identified as potential causes of this syndrome; however, mutations in other genes, particularly in the α1 subunit of the skeletal DHPR, have also been reported to generate MH episodes . This syndrome therefore emphasizes the central role that RyRs and DHPRs play in EC coupling. Interestingly, the great majority of RYR1 mutations seem to be clustered in three 'hot spots', namely, near the N-terminal (Cys35-Arg614), the central (Asp2129-Arg2458) and near the C-terminal (Ile3916-Ala4942) domains of the channel, a clustering that is repeated in an analogous RyR2-associated syndrome  (see below).
Porcine stress syndrome (PSS), which also results from point mutations of RYR1 (most often R615C) , is a similar MH syndrome, but with a wider array of triggering events (e.g. exercise, parturition, overcrowding). Susceptible pigs have been invaluable models to elucidate the molecular basis of MH in humans. Caffeine, which sensitizes RyR1 to Ca2+, elicits contractures of muscle strips of MH pigs at a lower dose than that required in control muscle. Caffeine hypersensitivity is also seen in human MH , and constitutes the basis for a clinical test of susceptibility. The bell-shaped Ca2+-dependence of [3H]ryanodine binding of MH-susceptible pigs is wider than that of normal pigs, suggesting greater sensitivity of RyR1 to Ca2+ activation and increased resistance to Ca2+ inactivation . At the single channel level, RyR1s from MH-susceptible pigs exhibit similar conductance to 'normal' RyR1s, but they display longer mean open time and require higher [Ca2+] for inactivation. All these findings point to greater Ca2+ mobilization from RyR1-controlled pathways during resting and contracting periods, with the resultant overflowing of cytosolic compartments with Ca2+, and the ignition of multiple signaling mechanisms. Heat seems to stem from the rampant hydrolysis of ATP by the SR Ca2+ pump and other active Ca2+ transporters trying to reestablish Ca2+ homeostasis. However, the pathway to MH-associated heat production may be much more complex, as shown by the finding that MH mutations cause not only Ca2+ dysregulation, but also an increased release of cytokines (for example, interleukin 6). In sufficiently large quantities, these cytokines can be pyrogenic .
Central core disease (CCD) is another autosomal-dominant myopathy resulting from mutations in RYR1[127, 128]. Although some patients with MH may show clinical myopathies before an MH episode, histopathological lesions characterized by pale staining of the central area of muscle fibers are necessary to diagnose CCD. Non-progressive muscle weakness, hypotonia and motor deficiencies are present in most, but not all, patients with CCD . Type 1 skeletal muscle fibers are preferentially affected, with central areas lacking mitochondria and their oxidative enzymes, thus staining poorly with basophilic dyes . The cause for the disappearance of central mitochondria is unknown. A potential explanation is that the RYR1 mutation, as in MH, causes excessive Ca2+ leak. In the periphery of the fiber, Ca2+-extrusion mechanisms would be sufficient to remove the excess Ca2+, but the central areas would remain vulnerable to local Ca2+ gradients. Central mitochondria would, therefore, 'swallow' greater amounts of Ca2+ than they could handle, leading to swelling and death .
An alternative model for core formation has been proposed, based on studies using a knock-in mouse heterozygously expressing a leaky-channel mutation in the RyR1 N-terminal region [118, 132–135]. According to this model, Ca2+ leak in the SR triggers the release of reactive oxygen and nitrogen species (ROS/RNS), causing RYR1 S-nitrosylation and glutathionylation, modifications that further enhance SR Ca2+ leak and RyR heat sensitivity. The authors correlated the resulting cascade of deterioration with the formation of cores that progress through a series of histopathologically distinct stages as the mice age. They proposed that oxidative damage, Ca2+-dependent proteolysis, and extreme stretching of the myofilaments due to prolonged contracture in the presence of unsequestered Ca2+ may all contribute to the progression of the disease. Importantly, these mice are prone to fulminant MH-like responses to heat challenge and halothane exposure [118, 135].
An entirely different mechanism for the muscle weakness associated with CCD was revealed in recent studies using a mouse knock-in model expressing a heterozygous mutation in the RyR1 ion pore . Muscle fibers from these mice exhibited reduced maximal twitch contraction, slowed rate of force development  and reduced global Ca2+ transients . Adult mice displayed weakened upper body and grip strength . These results were attributed to reduced and slowed RYR1 Ca2+ release, without change in either SR Ca2+ content or RyR1 sensitivity to activation by voltage or caffeine ; this pathway to CCD-associated muscle weakness is known as EC uncoupling . Unlike the leaky-channel knock-ins, these mice were not prone to developing MH-like symptoms.
Surprisingly, the same mutation produced dramatically different phenotypes in different strains of mice, experimental approaches, and expression systems [136–138]. Similarly, identical RYR1 mutations cause MH in some human patients and CCD in others. The mechanism(s) that leads to the different phenotypes remains a mystery. Very interesting, however, is the observation that patients with MH who lack clinical myopathies are more likely to have mutations at the N-terminus of RYR1, whereas those with clinical myopathies are likely to have mutations at the C-terminus . Although these observations seem to suggest that mutation mapping could provide an attractively simple predictor of phenotype, this notion probably oversimplifies the complexity of the problem. Transition from MH to CCD is probably a function of the severity of Ca2+ leakage, as the studies discussed above have shown that both C-terminal and N-terminal mutations are capable of producing this type of RyR1 dysfunction.
CPVT is an autosomal-dominant inherited cardiac disease characterized by exercise- or stress-induced tachyarrhythmia episodes in the absence of apparent structural heart disease or prolonged QT interval [139, 140]. The disease is rare but very malignant, often presenting for the first time in childhood and adolescence as syncopal events and/or sudden cardiac arrest. Multiple electrocardiographic irregularities (polymorphic) are simultaneously present in patients with this syndrome. More than 70 different mutations in RYR2, the gene encoding the cardiac isoform of RyRs, have been associated with CPVT , which is characterized by: a) more than two types of ventricular tachycardia morphologies, b) absence of underlying organic heart disease and c) absence of primary electrical disease (long QT, Brugada syndrome) . CPVT usually occurs during intense exercise or acute emotional stress, and may lead to sudden cardiac death. As in MH, excessive Ca2+ release from the SR, especially during diastole, seems to be the underlying mechanism that gives rise to the VT [143, 144]. Enhanced diastolic Ca2+ leak may overload the Na+/Ca2+ exchanger, which generates an inward current as it extrudes the released Ca2+. The inward current, in turn, gradually depolarizes the cell to threshold, favoring delayed after depolarizations (DADs) . During depolarization, lack of Ca2+-dependent inactivation of ICa due to previous depletion of the SR leads to higher Ca2+ entry and reloading of the SR, which triggers another DAD in the next beat. Successive repetition of this altered Ca2+ cycle could result in paroxysmal tachycardia and arrhythmias even if only a few foci of ventricular cells are involved.
Although this hypothetical scheme logically relates RyR2 dysfunction with VT, it is unclear exactly what mechanism induces a group of apparently normal RyR2s to behave aberrantly and to generate sudden tachycardia. Because infusion of catecholamines also triggers CPVT, it is likely that activation of the β-adrenergic system plays an important role. In this regard, it has been suggested that phosphorylation of RyR2 by PKA, the kinase linking β1-adrenergic receptor activation to cellular effects, dissociates FKBP12.6 [37, 90, 91, 146]), an accessory protein that presumably stabilizes RyR2 in the closed state. Phosphorylation of a mutant RyR2 would therefore remove a stabilizer from a channel on the verge of dysfunction, and would cause the pathogenic events described above. However, several studies have not found any evidence of FKBP12.6 dissociation in CPVT mutation-carrying RyR2 [147, 148]. Thus, structural alterations of the RyR2 channel complex seem to be more important than dysregulation by accessory factors in the pathogenesis of CPVT. Consistent with this notion is the fact that CPVT-associated mutations of RYR2 occur in domains corresponding exactly to mutation-containing domains that give rise to MH [123, 141]. Although some of these mutations are close to the apparent FKBP12.x-binding domain, the great majority are not. Recent studies point to a predominant role of Purkinje cells in the genesis of ventricular arrhythmias [149–151]. Whatever the triggering mechanism, SR Ca2+ load and release seem to be crucial, because mutations in CSQ2, the gene encoding cardiac calsequestrin, an intraluminal Ca2+ buffering protein that regulates RyR2 activity, also generate CPVT . Accordingly, a prominent hypothesis, championed mainly by Chen and collaborators, proposes that cardiac myocytes have a threshold SR Ca2+ load for spontaneous Ca2+ release, and that CPVT-associated mutations decrease the sensitivity to luminal Ca2+ (that is, decrease the threshold) [143, 153]. Thus, during β-adrenergic stimulation, when SR Ca2+ load increases as a result of enhanced Ca2+ entry and uptake, CPVT mutant channels reach their threshold and generate spontaneous Ca2+-release waves, creating a substrate favorable for Ca2+-dependent arrhythmias. Alternatively, CPVT-related mutations could increase the SR load, making it easier to reach the threshold upon adrenergic stimulation .
HF is a multifactorial syndrome characterized by contractile dysfunction and pathological myocardial remodeling. There is growing consensus that Ca2+ mishandling in HF leads to altered gene transcription, resulting in maladaptive structural transformations (cardiac hypertrophy and then wall thinning) that eventually hamper basic cardiac function . As with the genetic RyR dysfunctions discussed above, an enhanced diastolic Ca2+ leak seems to be central in the pathogenesis of some forms of HF . According to a prominent hypothesis spearheaded by Marx et al., increased catecholamine levels in patients with HF activate cAMP-dependent PKA by binding to β1-adrenergic receptors. PKA, in turn, phosphorylates RyR2-Ser2808 and dissociates FKBP12.6, increasing the probability of channel opening by inducing the appearance of long-lasting subconducting states. In this scheme, RyR2 hyperphosphorylation (up to 800% of control ) causes the enhanced diastolic Ca2+ leak. Unfortunately, this mechanism remains controversial. Although a few studies support some aspects of this mechanism, most groups have not been able to reproduce the central tenets of this hypothesis. Although Jiang et al. reported that PKA and the drug JTV519 both decreased FKBP12.6 binding to RyR2 , several other groups found that PKA phosphorylation of RyR2-S2808 neither dissociated FKBP12.6 nor substantially modified channel gating [88, 89, 94, 97, 158, 159]. Ai et al. reported that RyR2-S2808 phosphorylation was increased by approximately 50% in a rabbit model of HF; however, a direct test of PKA phosphorylation of RyR2 in canine and human HF yielded no difference compared with control, and a phospho-antibody against RyR2-S2808 detected equal phosphorylation levels in control and HF samples [158, 161]. More recently, a mouse with genetic ablation of the RyR2-S2808 site (S2808A), supposedly stabilized in the closed state by close association with FKBP12.6, displayed normal β-adrenergic response and similar progression towards heart failure compared with wild-type mice [88, 159]. Finally, FKBP12.0 dissociation of RyR1 is consistently reported to destabilize channel closure, but at least two groups failed to detect effects of FKBP12.6 dissociation of RyR2 [38, 162]. Clearly, more studies are needed to resolve these conflicting results and clarify the potential role of FKBP12.6, SR Ca2+ leak, and PKA phosphorylation of RyR2-S2808 in HF.
In addition to providing the majority of the Ca2+ necessary for contraction of cardiac and skeletal muscle, RyRs act as molecular switchboards that integrate a multitude of cytosolic signals such as dynamic and steady Ca2+ fluctuations, β-adrenergic stimulation (phosphorylation), nitrosylation and metabolic states, and transduce these signals to the channel pore to release appropriate amounts of Ca2+. Furthermore, because Ca2+ release is crucially modulated by luminal factors such as SR Ca2+ content and protein-protein interactions, RyRs play an additional role as integrative switch-valves that offset cytosolic-luminal Ca2+ imbalances. Thus, there is an ample margin to interfere with the activity of RyRs. In both experimental and natural conditions, such interference results in overt contractile dysfunction and gross morphological changes. MH, CCD and CPVT are among the most studied clinical presentations of RyR dysfunction, and the elucidation of the precise molecular mechanisms affected by this dysfunction is advancing with great strides.
EM, RL and HV contributed equally to the writing of this review. All authors read and approved the manuscript.


text:
module FinAnSu
  module DayCount
    class << self
      attr_reader :days_per_month, :days_per_year

      def initialize(days_per_month, days_per_year)
        @days_per_month, @days_per_year = days_per_month, days_per_year
      end
    end

    class Act360

    end
  end
end

redpajama_set_name: RedPajamaGithub


text:
Victory for Environment as Karoo Fracking Dealt Setback in South African Supreme Court Ruling
Kruger Park Visitor's Message for Good Samaritans Goes Viral
Botswana Brings Back Hunting, Reducing Elephants to a Political Football
WATCH Flood Report as Ramaphosa Declares National Period of Mourning in South Africa
More Than 50 Dead After Heavy Rains in South Africa
What Cape Town's Drought can Teach Other Cities about Climate Adaptation
Extreme weather events, such as Cyclone Idai that has recently devastated Beira, Mozambique, and Hurricane Harvey that hit Houston, USA, in 2017 are the...
Cyclone Idai's Death Toll Rises to 843. Hunger Stalks Mozambique.
BEIRA, Mozambique - Hundreds of thousands of people are in need of food, water and shelter after Cyclone Idai battered Mozambique, Zimbabwe and Malawi....
Why Kenya Must Take Control of Sand Harvesting Off Its Coast
Kenyans have taken to social media to protest against what they claim is illegal sand harvesting off Diani beach, one of the country's most...
Amateur SA Botanist: Do Yourself a Favour and Plant a Marula...
The Marula tree (Sclerocarya birrea) is a local alternative to the Jacarandas and Madagascan Flamboyants. Jacarandas and Flamboyants are some of my pet peeves...
Joburg's 10 Million Tree Canopy Under SERIOUS Threat. Here's What You...
Johannesburg is famous for having one of the largest urban forests in the world, but now the South African city faces losing much of...
PHOTOS Magical Mushrooms in Barberton's World Heritage Makhonjwa Mountains, South Africa
Once upon a time... in a beautiful forest on the magical Barberton Makhonjwa Mountains... writes Sheryn Nader who took these beautiful photographs of nature's...
Former NY Mayor Bloomberg to Forgo 2020 White House Bid, Will...
Former New York City Mayor Michael Bloomberg will not seek the Democratic nomination for U.S. president in 2020 but will instead launch an effort...
WATCH: Epic Wingsuit Flight From SA's Majestic Drakensberg
In this 14 minute video account the Red Bull Air Force takes to the skies from the Drakensberg Mountain Range in South Africa flying...
Working Towards a Clean SA
Government is set to launch a ground-breaking initiative that seeks to mobilize all South Africans to become more environmentally conscious. Dubbed the Good Green Deeds...
Cape Town Has a Plan to Manage its Water. But There...
The City of Cape Town – and southwest Africa more generally – experienced its worst drought on record between 2015 and 2018. With fresh...


Picture those furniture ads with their matching sofas, love seats, and recliners, along with their twin end tables and two identical lamps. These types of design decisions are easy because there's little risk involved. You know it will look good because it looks good in the ad. But if the room becomes too predictable, it can become dull and lack personality.
Solution: Stay within your color palette, but don't be afraid to gently mix textures, patterns, and metals-chenille with leather, flowers with pinstripes, bronzes with pewters. Then add a couple of little surprises, such as an antique Chinese red table to complement the sofa or some Turkish pottery to hold a bouquet of wildflowers. Result: instant pizzazz.


Carob Syrup | Australian Carob Powder | Wholesale Carob | The Australian Carob Co.
Syrup pure is naturally sweet and is of the highest quality. The syrup is great to use on breakfast cereals as an alternative to sugar. It is also perfect as a topping for desserts, to pour over pikelets or pancakes, marinating meat, or as a sweetener in hot or cold drinks.
Try cooking the carob syrup cake in the recipe page which is compliments of (Fast Ed).
Organically Grown Carob and Water.


text:
Das Ciudad Emergente, auch Festival Ciudad Emergente (zu deutsch: Aufstrebende Stadt), ist ein mehrtägiges Festival, welches seit 2008 jährlich im Sommer an mehreren Plätzen in der argentinischen Hauptstadt Buenos Aires ausgetragen wird.

Hauptträger ist die Stadtverwaltung Buenos Aires, Hauptveranstaltungsort ist das Centro Cultural Recoleta. Das Programm erstreckt sich über Rock- und Popmusik, Dichterlesungen, Fotografie, Comedy und Film.

Ausgabe 1, 2008

Das erste Festival fand vom 21. bis 29. Juni 2008 statt. Als Film wurde u. a. Feiern – Don't forget to go home von Maja Classen (2006) gezeigt.

Ausgabe 2, 2009

Daten des zweiten Festivals: 11. bis 15. Juni 2009.

Ausgabe 3, 2010

Daten des dritten Festivals: 2. bis 6. Juni 2010. Erstmals wurden 130.000 Teilnehmer verzeichnet.

Ausgabe 4, 2011

Daten des vierten Festivals: 16. bis 20. Juni 2011 mit 160.000 Besuchern.

Ausgabe 5, 2012

Daten des fünften Festivals: 6. bis 10. Juni 2012 mit 250.000 Besuchern.

Ausgabe 6, 2013

Daten des sechsten Festivals: 19. bis 23. Juni 2013 mit 350.000 Besuchern über fünf Tage.

Ausgabe 7, 2014

Für die siebte Ausgabe des Festivals vom 4. bis 8. Juni 2014 wurden mehr als 250.000 Besucher erwartet, letztlich nahmen laut TN.com.ar sogar mehr als 300.000 Besucher teil, während die Festivalleitung die Teilnehmerzahl mit über 350.000 angibt.

Mitte Mai 2014 wurde das musikalische Rahmenprogramm vorgestellt. Ein Höhepunkt war die Vorstellung des Showtheaters Fuerza Bruta. Einen Auftritt hatte am 8. Juni 2014 auch die Post-Hardcore-Band Deny.

Vom 21. bis 23. Mai 2014 fand das erste Festival Ciudad Emergente in der Stadt Córdoba in Argentinien statt.

Anmerkung: Das Festival ist nicht zu verwechseln mit dem 2011 gegründeten gleichnamigen webbasierten Stadtentwicklungsprojekt Ciudad Emergente (CEM).

Weblinks

 Festival Ciudad Emergente auf der Website der Stadt Buenos Aires

Einzelnachweise

Musik (Buenos Aires)
Musikfestival in Argentinien
Erstveranstaltung 2008


text:
Trust in public cloud providers' security is increasing
Enhanced security measures are encouraging use of cloud computing
by: Zach Cooper
End user apprehension towards moving to the cloud is dissipating, according to an IDG Connect survey. Of those polled, half felt more confident in migrating workloads off-premise, a trend that can be attested to stronger security measures on both the vendor's side and the end user's side.
Since its inception, cloud computing has forged paths towards efficiency and enhanced customer experiences, enabling the digital transformation necessary to ensure businesses remain competitive. Storing data and applications in the cloud though, brought to the surface a host of security issues that have dissuaded many IT decision makers from transitioning.
What to look for in a secure cloud system
What is cloud security?
CISOs now say cloud technology is 'just as safe' as on-prem
Cloud providers do offer security layers that end users can take advantage of to shore up vulnerabilities, yet despite this, a lack of understanding and expertise within IT departments has led to many organisations struggling to deploy the security measures, which are often complex and require specific knowledge. The result is vulnerable data and applications. Paired with severe breaches hitting the headlines regularly throughout 2018 and 2019, it is no surprise that many companies were hesitant to store their applications and data off-premise.
In response to end users' fears, vendors are implementing stricter security controls which can restrict access to data centres, ensuring only those who need to access are granted access. This eliminates internal vulnerabilities by preventing the wrong employees stumbling upon information that wasn't meant for their eyes.
Microsoft is taking a leap further: Integrating its Azure compute infrastructure with customised hardware components with embedded protection against unauthorised access, also reducing complexity by providing a one-pane solution. Additional security layers are provided by partner-companies feeding into the original vendor's cloud offering. In the Microsoft example, Red Hat, the open source software specialist, is protecting workloads at the virtualisation and application application levels.
Vendors are also taking it upon themselves to test their security features regularly. Penetration testing has developed out of the ethical hacking concept, allowing vendors to realise vulnerabilities in their software before the chinks can be targeted by malicious hackers.
IDG's survey reveals that these measures are feeding back to customers. In addition to the 50% reporting confidence in transitioning to the cloud, 58% indicated that they trust public cloud providers' data security platforms and protocols rather than their own IT departments, while 54% implied they weren't worried about losing control over application and infrastructure provisioning and management as a result of cloud migration projects.
For vendors, existing customers are happy and retained, and new customers are attracted. And with security remaining a top priority for software companies, cloud computing may continue it's surge in popularity for years to come.


Okay then, so for now and here we go! It's Kingdom Hearts 3D: Dream Drop Distance with Daisy Duck the voice clips. Oh well... I hope she wasn't there on Kingdom Hearts 3D: Dream Drop Distance anymore. And so you see, Daisy Duck is so very pretty nice girl duck!


East Atlantic Avenue in Delray Beach, between Swinton Avenue and the Ocean, is the most happening mile of restaurants in Palm Beach County. Atlantic Ave has grown to encompass the surrounding streets and revitalized downtown area. Notable restaurants include; 32 East, Caffe Martier, Prime, Vic & Angelo's, Cut 32, City Oyster & Atlantic Grill.