POPULARITY
durée : 00:04:16 - Ici et là avec Lisa Huth du Saarländischer Rundfunk - Lisa Huth nous détaille le programme de l'émission "Ici et là " du SR2
Ion channel block unraveled Transcript of this podcastHello and welcome to the NanoLSI podcast. Thank you for joining us today. In this episode we feature the latest research by Takashi Sumikama at the Kanazawa University NanoLSI in collaboration with Katsumasa Irie from Wakayama Medical University and colleagues.The research described in this podcast was published in Nature Communications in July 2023 Kanazawa University NanoLSI websitehttps://nanolsi.kanazawa-u.ac.jp/en/Ion channel block unraveledResearchers at Kanazawa University report in Nature Communications how calcium ions can block sodium ion channels located in cell membranes. Structural analysis and computer simulations made it possible to identify where and why calcium ions get stuck. Ion channels are structures within cell membranes that enable specific ions to travel to and from the cell. Such transfer is essential for a variety of physiological processes like muscle cell contraction and nerve excitation. In so-called tetrameric cation channels, the ion selectivity results from the unique structural and chemical environment of the part referred to as the selectivity filter, which is located between two intertwined helical structures. Tetrameric ion channels are prone to ‘divalent cation block', the blocking of the channel by ions like calcium (as in Ca2+). Such blocking regulates the ionic current, which is involved in various neural activities such as memory formation. How divalent cation block happens exactly is still unclear at the moment — in particular, a direct observation of the cation actually blocking the ion pathway has not been reported yet. Now, Takashi Sumikama from Kanazawa University in collaboration with Katsumasa Irie from Wakayama Medical University and colleagues has discovered the mechanism behind divalent cation block in NavAb, a well-known tetrameric sodium (Na) channel. Through structural analysis and computer simulations, the researchers were able to reveal the relevant structural features and molecular processes at play.So how did they go about this structural analysis?NavAb is a sodium channel cloned from a bacterium (Arcobacter butzleri) and has a well-known structure. Sumikama and Irie's colleagues performed experiments with NavAb and three mutants. The structures of the mutants were determined for environments with and without calcium. The scientists focused on the differences in electron densities for the different structures, as these provide insights into the locations of the calcium ions. They found that for the mutants displaying calcium blocking, one or two calcium ions are located at the bottom of the selectivity filter. They also discovered that two other divalent cations — magnesium (as in Mg2+) and strontium (Sr2+) ions — blocked the calcium-blocking mutant sodium channels.The researchers then performed computer simulations to obtain a detailed understanding of the interaction between the calcium ions and the mutated NavAb channels. The simulations reproduce the dynamics of ions passing — or not passing — the channel. In the absence of calcium ions, sodium ions were observed to penetrate the channel. In the presence of calcium ions, penetration significantly decreased in the calcium-blocking mutants. The simulations also confirmed that the blocking calcium ions are ‘stuck' at the bottom of the selectivity filter, and revealed that this ‘sticking' is related to the increased hydrophilicity (affinity to water) of relevant structural parts of the mutated channels.The results of Sumikama and Irie's colleagues provide an important step forward towards a full understanding of the mechanism of divalent cation block in NavAb, an important and representaNanoLSI Podcast website
USPAP and the investigator's questions is a topic we've covered before. But investigators still keep asking questions. So it makes sense to be aware of them, as well as how to answer them. That raises the question, "How do I answer the investigator's questions?". There is a two-part answer: part one is "from the data in your workfile". Part two is "and those data in your workfile must have market support". Remember, if you can't find it in the market, why is it in your appraisal? If you can't find it in your workfile (which is your appraisal), why is it in your report? Note there are classes to help you with this. To use the term "USPAP and The Investigator's Questions" implies USPAP is the source of the investigator's questions. That's because USPAP is that source. So are the state's appraisal statutes. But most of the questions are from USPAP. Why? Simply because USPAP is the standard. Does your appraisal meet Standard Rule 1? Does you appraisal report meet Standard Rule 2? If so, you are good to go. If not, there are ramifications to consider. Here is but one example of USPAP and the investigator's questions. "From only the data in your workfile, please demonstrate the derivation of your GLA adjustment of X-dollars per square foot." As far as the investigator's questions go, this one is simple and straightforward. However, the issue is that, all too often, this derivation is not in the workfile. That adjustment is, instead, the result of rules-of-thumb and the appraiser's "...twenty years of experience...". Since the dollar amount of the GLA adjustment is one the market indicates, it is a fact, not an opinion. USPAP's SR2-3 makes it clear the appraiser certifies this dollar amount is both "...true and correct...". This means verification. And how can an appraiser certify something is true and correct if there is no verification in the workfile of that fact?
USPAP and adjustments. Are they facts or just your opinion? USPAP does not use the word adjust or adjustments in Standard One, the appraisal development standard, nor Standard Two, the appraisal reporting standard. Further, USPAP does not require appraisers to make them to anything at any time. They are a function of what the GSE's want from an appraisal report. So, when it comes to USPAP and adjustments, are those adjustments facts or just opinions? There are appraisers who advocate they are opinions. Why? Because there are no standard protocols to derive an adjustment. There are numerous ways to derive individual adjustments. Because of this lack of standardization, so long as there is market support for the adjustment you make, it is just your opinion, right? Market support? USPAP and adjustments means you have market support for them. Since there is such support, that means you extracted them from the market. Given that the market revealed to you that swimming pool adjustment, that is a market-derived fact, not your opinion. Any facts we report must, according to SR2-3, be both true and correct. This requires verification. We verify facts. We confirm opinions. So, with USPAP and adjustments, are they facts or opinions? There are classes you can take to help you answer this question. There are USPAP instructors out there you can contact who will help you navigate your way to an answer to this question. But the point is (and any state appraisal board member will tell you this) be adjustments facts or opinions, they must have market support. Without that support, they are nothing more than guesses. So, gather your data, do your due diligence, and make your decision. In the end, when it comes to USPAP and adjustments, I think you'll agree with me: there are facts to be found.
Does USPAP demand precision? This is a question few appraisers have raised, so there is no specific answer to it. USPAP itself uses the word precision just once, in AO-23, but in the context of a discounted cash flow analysis. It uses precise only four times. But only one of those is in Standard 1. None of them is in Standard 2. And its use in Standard 1 is in the context of a precise definition of value. USPAP does not use the term in the context of the value opinion itself. But, does USPAP demand precision anywhere in Standard 2 (the report writing standard), in any context? Directly, no it does not. However, SR2-1 demands the appraisal report be clear and accurate so that it is not misleading. That same SR also makes it clear the client and the intended user(s) must be able to "...understand the [appraisal] report properly..." no matter the reporting format. So, in an off-handed manner, USPAP does demand precision, although that call could be clearer and more emphatic. So, the question, "Does USPAP Demand Precision?" raises another question: "What is precise?", which this podcast's purpose is to illustrate with a series of questions. For example, in twenty (-20-) words or less, answer this question: "In the final reconciliation, why did sale-X deserve more weight than sale-Y?" Here is another one: "In twenty (-20-) words or less, explain why appraisers develop value opinions, rather than provide estimates of value". There are so many more. "Does USPAP Demand Precision?" may be too emphatic. Perhaps a more applicable question is, "Does USPAP Encourage Precision?" Given what Standard 2 says about not misleading the client, about writing the report so it is easy to understand, it looks as if the answer is in the affirmative. So, why is it that we appraisers should write precisely? (In the podcast, I mention Einstein's E=MC-squared formula. Here is an explanatory link).
In Episode 84, The 966 speaks with Faisal Durrani, partner and head of Middle East research for the global real estate company Knight Frank. Mr. Durrani shares some of the highlights and key information from Knight Frank's recently-released 2023 report on real estate in Saudi Arabia, The Saudi Report 2023, a publication which touches on many subjects beyond real estate, including hotels and tourism, travel preferences for Saudis domestically, and so much more. Before the conversation, the hosts discuss the situation in Sudan and Saudi Arabia's role in assisting other nations in getting its civilians out of harms way in the country, how a Saudi company became ensnared in the politics of the Western US water crisis, and much more. 4:01 - Richard's one big thing is Saudi Arabia's assistance in getting civilians out of harms way in the war-torn country. Sudan is just across the Red Sea from Saudi Arabia, and both nations share a long border with that pivotal trade route, raising the stakes for the Kingdom as yet another nation in its neighborhood is threatened with instability. Sudan has a 530-mile (853 km) coastline bordering the Red Sea, and that waterway's maximum width is 190 miles. There are fears that the fighting could further fragment the country, worsen political turbulence and draw in neighboring states. Saudi Arabia received praise from U.S. President Joe Biden for its work and hospitality in rescuing civilians from harm's way. 12:04 - Lucien's one big thing is the water crisis in the American west, and how it has ensnared a Saudi company, Fondomonte, a subsidiary of Almarai, the Kingdom's largest big agricultural company. Saudi Arabia's own water conservation has lead Saudi Arabia to explore farming and agriculture opportunities abroad, both in wheat and other imports from places like Ukraine and in Africa, and in agricultural enterprises abroad, including in the United States. Fondomonte in Arizona farms alfalfa to feed cows for dairy products in the Kingdom. Fondomonte had permitting applications into the state for drilling the wells but those were denied ceremoniously by the state's attorney general, Kris Mayes, who used the opportunity to make an example of Saudi Arabia's farms in Arizona and the need for water to be used by locals. The permits were denied after Hays raised objections in early April to state agencies about discrepancies in application paperwork, including listing different landowners and conflicting information about whether the wells were new or replacements,” azcentral.com reports. Valued at $14.3 billion, the Almarai Company – which owns about 10,000 acres of farmland in Arizona under its subsidiary, Fondomonte – is one of the biggest players in the Middle East's dairy supply. The company also owns about 3,500 acres in agriculture-heavy Southern California, according to public land records, where they use Colorado River water to irrigate crops.26:28 - The 966 speaks with Faisal Durrani, partner and head of Middle East research for the global real estate company Knight Frank. Mr. Durrani shares some of the highlights and key information from Knight Frank's recently-released 2023 report on real estate in Saudi Arabia, The Saudi Report 2023, a publication which touches on many subjects beyond real estate, including hotels and tourism, travel preferences for Saudis domestically, and so much more. 1:12:07 - Yallah! 6 top storylines to get you up to speed on all things Saudi headed into the weekend. World Military Spending Rises to Record as Insecurity SwellsDefense expenditure increased by 3.7% in real terms to reach a record high of $2.24 trillion in 2022, the Stockholm International Peace Research Institute, SIPRI, said on Monday. About half the annual increase was due to Ukraine's ballooning military budget, according to data for the eastern European country that excludes foreign aid. Arms budgets are expanding across Europe in response to Russia's aggression at the same time as tensions in East Asia are prompting larger outlays in that part of the world. In another sign of how the world is sliding back into a situation last seen during the Cold War, military expenditure in central and western European countries exceeded the 1989 level for the first time.Saudi Arabia Advances 17 Ranks in World Bank's Logistics Performance IndexSaudi Arabia, which came in at 38, was ranked 55 in the 2018 report, and has seen its stock as a global logistics hub rise as it formulates plans for as many as 60 logistics hubs around the Kingdom, and contemplates wholesale upgrades of existing ports, as well as a number of greenfield facilities. Identical rankings to Saudi Arabia were achieved by India, Lithuania, Portugal and Turkey, also all ranked 38-equal, with identical overall LPI scores of 3.4. The rankings were topped by Singapore, with a score of 4.2, with Finland coming second, also on 4.2 and Denmark third, with 4.1Saudis constitute 82.2% of workforce in financial and insurance activitiesReflecting the success of localization efforts, Saudis constituted 82.2 percent of the number of workers in the financial and insurance sectors in 2022. Saudi citizens who are working in financial and insurance activities reached 75,001, while foreigners totaled only 16,290 or 17.8 percent, bringing the total number of workers to 91,291 last year. Male workers made up 93 percent of the workforce in financial and insurance activities – reaching 71,648 workers in 2022, while the number of females working in these activities hit 19,643, according to Al-Eqtisadiyah. Saudi Public Investment Fund ranks 5th with worth $620bnThe ranking of Saudi Arabia's Public Investment Fund (PIF) has improved from sixth to fifth place among the largest sovereign funds in the world for the first time, with assets valued at SR2.3 trillion ($620 billion). The fund's share of the world's sovereign wealth has increased to 6.2%, up from 5.9%, according to Arab News.Unemployment in Saudi Arabia Reaches Record Low with Women Driving the Change — Jadwa InvestmentThe unemployment rate in Saudi Arabia dropped to 8 percent at the end of 2022, down from 11 percent in 2021, with women driving that positive change, according to a recently-released report from Jadwa Investment, citing the General Authority for Statistics' (GaStat) latest labor market release.Female unemployment was down to 15.4 percent in 2022 versus 22.5 percent in the previous year.Saudi Arabia is building more hotels than UAE for the first timeAccording to a report in Hotelier Middle East, the UAE is no longer the regional leader when it comes to building hotels. "According to STR, Saudi Arabia has almost double the number of hotel rooms being built than the UAE. Saudi sits behind only China and the US globally in terms of the number of hotel rooms currently being built."
Dr. Sky Steve Kates - Lockheed Martin, Son of Blackbird, SR2 by John Catsimatidis
Also my new EP, "SR2" is finally out this Friday! Go stream it! --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/thesolomonraypodcast/message
In this episode, you'll hear from Susan LaBarr, composer of "Hold Fast to Dreams" - available for SATB and SSA through Santa Barbara Music Publishing. Susan and I discuss the conception of the piece, dotted quarter notes, commissioning, and the usual non-musical banter. Thank you so much for listening and I hope you check out Susan's choral music catalogue! https://www.giamusic.com/store/walton-music-editor SSA - https://sbmp.com/SR2.php?CatalogNumber=1426 SATB - https://sbmp.com/SR2.php?CatalogNumber=1136
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Are there really three USPAP secrets you need to know? What are they? Why are they secrets? Is The Appraiser's Advocate website the only place I can find them? OK! Enough questions! What are the secrets about extraordinary assumptions and hypothetical conditions I need to know? First, the three USPAP secrets are not really secrets. They are there for anybody willing to do the research to find them. They are not even really hard to find. All you have to do is look! These so-called secrets have to do with their definitions, when to use them, and how to disclose them. For details, you'll need to listen to the podcast. But it is possible to reveal that, by definition, there is no such thing as a generic extraordinary assumption. Since the three USPAP secrets are not really secrets, why call them secrets? True, they are not secret. But appraisers use them improperly so much of the time, it is as if they were secrets. There are plenty of places to go for advice on appraisal questions and issues. But sometimes, old Mother USPAP is the best place to start. Start where? How about the definitions of extraordinary assumption and hypothetical condition. Then, how about SR1-2(f, g) for a description of the only circumstances you can use one or the other. Then, finally, SR2-2(a)(xiii) for proper disclosure protocols. See! There aren't three USPAP secrets. They are right there in the open. All you have to do is look for them. Thanks for listening!
This is Derek Miller, Speaking on Business. Located just up Little Cottonwood Canyon, Snowbird has been spinning the bowl wheels of its iconic aerial tram and providing world-class recreation for nearly 50 years. Here to tell us more is president of Snowbird, Dave Fields. Snowbird is a proud and grateful member of our community and we are looking forward to welcoming everyone back to the mountain next season for our golden anniversary. If the past 50 years have taught us anything at Snowbird, it's the importance of preserving our community, mountain, environment and the experience of those who come to the canyon to recreate. One of the largest initiatives that we are working towards is the support of the Utah Department of Transportation's gondola option for Little Cottonwood Canyon transportation. SR2-10 is one of the most dangerous highways in North America. When snow falls in the canyon, it is not only subject to avalanches and road closures, but poor driving conditions that can jeopardize those on it. The UDOT gondola proposal could not only help avoid the need to drive on the road but provide a cleaner and more efficient way to get guests up the canyon directly. For us, this is a top priority. Get ready to celebrate Snowbird's golden anniversary, and to learn more about the Little Cottonwood Canyon gondola initiative, please visit snowbird.com. I'm Derek Miller with the Salt Lake Chamber, and this is Speaking on Business. Originally Aired: August 4, 2021.
Real estate appraisal boilerplate can be an advantage! Yet, it can save time, money, and effort. These are a plus to any appraiser, right? But is there a downside? Are there circumstances when boilerplate could be a problem? Unfortunately, yes, there are. While boilerplate has its advantages, it has some strong disadvantages, too. So strong, in fact, you may want to take a close look at your reports. It is way too easy to let generic boilerplate replace critical thought and analytics. When that happens we are not appraising. We're just filling out a form. An AVM can do that - for a whole lot less money than we charge! So, which real estate appraisal boilerplate should we avoid? In letters of transmittal, it's common to read the appraiser engaged in an economic analysis of the subject's neighborhood. Really!? That is a statement of fact. Per SR2-23 it therefore must be both true and correct. Really, did that appraiser carry-out an economic analysis of the subject's neighborhood? Maybe. But likely not. With rare exceptions, appraiser are not trained in the econometrics and statistics of such an analysis. To make that statement means those analyses are in the workfile. All the state investigator must do is find them. And if those analyses are not there? Let's just say that appraiser is going to have the opportunity to learn the depth of USPAP's definition of misleading. Is that the kind of learning experience the boots-on-the-ground appraiser really wants? Is there another example of real estate appraisal boilerplate? Highest and Best Use is another area to be careful of! There are at least three (3) B&BU models. In the 15th ed. of The Appraisal of Real Estate is the traditional four-component model (made even more complex by expanding to to an eight-component model. USPAP [see SR1-3(a)(i-v)] has a five-step model. But it is different from the model in the 15th edition. Fannie Mae has her own model, too. She says stop once you've shown the improvements add at least one net dollar to the value of the underlying site. But she is totally silent on which model to follow to conclude the H&BU of the vacant site. Remember, SR2-2(a)(x) obligates us ethically relative to H&BU. We have to summarize the support and rationale we developed to support those opinions. (Opinions?! Yes, both as vacant as as improved). Your software does not do this. Only you can write that summary and make it market- and subject-specific Real estate appraisal boilerplate is what you make available to your state board with every report you submit. You say, "Hello state appraisal board! Here's my boilerplate!" How deeply the state chooses to investigate is the state's call. But before you submit your next report, perhaps you'll want to ask yourself a question? Is that boilerplate relevant to a credible value conclusion? Or is it there because some long-past mentor told you to put it in? Does your boilerplate lead your client step-by-step to your value conclusion? If it does not, why is it in the report? If it does not, are you misleading your client by not leading the client anywhere at all? Think about it!
Claim your Hunted profile today with your exclusive and amazing offer which is only valid for Recruitment Rollercoaster Listeners! Use the code - ROLLERCOASTER25 to get a HUGE 25% off all of Hunted's annual subscriptions. https://portal.hunted.com/ (https://portal.hunted.com) If you're a recruiter then make sure you set yourself up a profile on https://www.hunted.com/ (https://www.hunted.com/) to get access to the best companies in the industry. On this episode I'm joined by Chris Sheard, Co-Founder of SR2 recruitment. After his dreams of being a professional golfer were starting to wane, he entered the world of sales, working at Computer Futures, part of the infamous Sthree group. He progressed up the ranks of many businesses, and experienced working in a start-up environment as well as for corporate giant Randstad. He then set up SR2 and in just under three years has grown it to over 15 consultants and a strong brand. For recruitment business owners who are interested in learning about hiring without a R2R, this one's for you. For the junior consultants out there, this is an excellent podcast to learn more about what it's like working for a corporate business as well as a start-up. You can connect with Chris on LinkedIn: https://www.linkedin.com/in/chrissheardsr2/ (https://www.linkedin.com/in/chrissheardsr2/) Timestamps: How did you get into recruitment? [1:11] What was the motivation to get into recruitment? [3:50] Opus [4:49] What's your opinion on Sthree culture? [5:46] Growing your career at Opus [8:12] How did you get the opportunities that you did? [9:15] What were your key learnings as a manager? [11:28] How many people did you lead? [14:08] Pros and cons of a startup and a corporate [17:12] Non-negotiables when starting your own business [18:56] What was the differentiator for SR2? [22:09] What runway did you give yourself when starting the business? [27:05] Key things that have been good investments [30:46] How much did you spend on marketing? [32:39] How much thought did you put into your brand? [34:13] Did you over communicate that you wouldn't be billing? [40:30] What were the key learnings going into year 2? [42:08] What was your mindset when hiring? [44:57] How have you cultivated your culture? [50:24] What's impacted your retention? [54:13] How did you finish in year 2? [55:55] What have been the challenges? [56:33] How has business been during this time? [1:01:02] How have you handled a potential divide? [1:06:14] Expectations for staff on furlough? [1:07:45] What's enabled you to build a strong business? [1:10:00] What are you excited about? [1:12:31] What would you say to the people? [1:13:43] I hope you enjoyed the episode, the best place to connect with me is on Linkedin - https://www.linkedin.com/in/hishemazzouz/ (https://www.linkedin.com/in/hishemazzouz/) If you would love me to cover certain topics with future guests please drop me a message. Finally, if you have been enjoying the podcast and you have two minutes then it would be greatly appreciated if you could leave a review. Simply it will enable me to reach more people with the podcast, you can easily leave a review with the following link - https://ratethispodcast.com/rollercoaster (https://ratethispodcast.com/rollercoaster)
Remote Sessions is the Mini-Series presented by the Getting It Done Podcast, which asks "How do you stay productive during a pandemic?" This episode we sit down with friend of the podcast and Managing Director of SR2, Chris Sheard. Chris shares his thought on remote working, his process of tackling the dreaded "to-do list" and what SR2 are doing to stay connected with each other! Be sure to follow us and subscribe to get all future episodes updates! ***All thoughts, opinions, and comments from those featured, including the host, are their own and not representative of the businesses, employers, brands or individuals they are connected to in any way.*** Contact: peopleup.info@gmail.com
On this episode, Andy and I answer some of our favorite messages that we've received from our beloved Stalkers. Facebook, Instagram, Twitter, you name it! We hear you and we are here to answer life's strangest questions: Why do some sounds feel like nails on a chalkboard? Why do I react so strongly to car horns? And my ~personal~ favorite, how long can you be mad at someone before you don't love them anymore? Give it a listen, send us your own thoughts/questions, and thank you for your support! As always, stay safe my friends. show notes —- http://www.upcpodcast.com/archive1/SR2
Confused over SR2-3, the Certification Standard? Tim Andersen, The Appraiser's Advocate, helps to alleviate that problem...and explains the difference between a fact and a conclusion, too
Hay muchos que están a favor de una dieta baja en carbohidratos, porque les ha ayudado a perder peso y sentirse mejor. Incluso encontrarás revistas y sitios web dedicados a estas dietas cetogénicas muy bajas en carbohidratos, con cientos de testimonios de personas que certifican sus bondades. Por otro lado, hay muchas personas, entre ellos deportistas y gente muy sana, que comen una dieta moderada o alta en carbohidratos. Y cuando han intentado restringir los carbohidratos en su dieta, se sienten fatal. ¿Es mejor comer más o menos carbohidratos para tu intestino? ¿Cuál de los dos grupos miente? Probablemente los dos tengan la razón. En el episodio de hoy hablamos de Las dietas altas y bajas en carbohidratos y cuál es la mejor para tu intestino Algunos alimentos ricos en carbohidratos que suelen dar menos problemas de intolerancias o síntomas digestivos Relación de la ingesta alta o baja de carbohidratos con la tiroides Algunos ejemplos de desayuno, almuerzo y cena altos y bajos en carbohidratos Los criterios a tener en cuenta para saber si debes comer una dieta alta o baja en carbohidratos Los criterios a tener en cuenta para saber si debes comer más o menos frecuentemente Algunos beneficios del ayuno intermitente para la salud intestinal Doctorcueva.com/episodio55 Notas del Episodio Sitio web con contenido nutricional de alimentos - Dietas.net Estudio sobre dieta baja en carbohidratos que mejoró autoinmunidad tiroidea - https://www.ncbi.nlm.nih.gov/pubmed/27747984 Estudios sobre beneficios del ayuno intermitente en Colon Irritable y Enfermedad Inflamatoria Intestinal - https://www.ncbi.nlm.nih.gov/pubmed/17078771 - http://www.indianjgastro.com/IJG_pdf/nov2008/nov08_SR2_pg239_acknowledge241.pdf Revisiones Sistemáticas sobre el ayuno, saltarse comidas y el peso: https://www.ncbi.nlm.nih.gov/pubmed/26024494 https://academic.oup.com/ajcn/article/102/2/464/4564588 Revisión sistemática que no encuentra un beneficio consistente de la típica recomendación de comer frecuentemente - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683169/ Membresía de Problemas Digestivos Si te gusta el podcast, nos ayudaría mucho que nos dejaras una valoración en iTunes (idealmente con un comentario amable y 5
Zeitgenössische Kunst in all ihren verschiedenen Ausdrucksformen gibt es aktuell auf der 11. Landeskunstausstellung SaarART zu sehen und zu hören. Malerei, Fotografie, Klangkunst, Performance und Urban Art ? alles ist vertreten.
Craps Journey | Dice Setting, Dice Control, Dice Influence & Betting Strategy
Casino : Treasury Brisbane $400 buy in 1/2 table right side SO and SR2 2 players 3V set and 2V set Just one other at the table today. I started slow to warm up but in the end it didn’t help. Shot myself in the foot repeated times with working on the come out going […]
Welcome to this weeks full episode of Space Dock Jury (number 32 not as Lee says on the cast 31 – idiot!) This week Lee brings a saucer in the form of the C57-D from Forbidden Planet, Andy returns to Mass Effect with hopefully less contentious return of the SSV Normandy with the SR2 from… Read more →
1913 erhielt die Pfarrkirche St. Johannes und Paulus in Beckingen eine neue Orgel, die spätromantische Klais-Orgel. Spätestens zu ihrem 100jährigen Jubiläum soll sie wieder in einen optimalen Zustand gebracht werden.
Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 02/06
In this study a structure–function analysis has been employed to analyze transcriptional regulation through the Mediator subunit MED25. A relationship could be established between predicted structural domains and functional characteristics of this protein. Most critically the region responsible for interaction of MED25 with the Mediator was identified. Immunoprecipitation experiments demonstrated that the so–called VWA domain (von–Willebrand A domain, amino acids 1–290) is both sufficient and required for this contact. Site–directed mutagenesis indicates that this binding reaction involves the non–conserved loop SR2, which is protruding from this domain. Based on the results of this analysis a model was proposed, in which the primary contact is established by ionic forces and is further stabilized by hydrophobic interactions. The previously identified ACID domain was reported to bind to VP16. Targeted mutagenesis of four different motifs in this region impaired not only transcriptional activation through MED25 but also led to reduced binding to VP16. In particluar a lysine–rich motif is also present in two domains of PTOV1, a close homolog of MED25. Noteworthy, K518 is not conserved in the PTOV1_B domain, which in contrast to PTOV1_A and the ACID domain of MED25 does not bind to VP16. This led to the hypothesis that K518 is critically involved in the binding of VP16 to MED25. Furthermore it could be demonstrated that MED25 contains an intrinsic transcriptional activation capacity, which is localized in the region 290–715. This indicates additional recruitment of other factors to promoters through this region. Together with the Mediator binding VWA–domain and the VP16–interaction domain this region might facilitate transcriptional activation. A genome–wide screen showed downregulation of c–Jun and FosB following overexpression of MED25. Interestingly, expression of GSK3β, a downstream target of which is cyclin D1, seems to be stimulated by MED25. Together with the finding that overexpression of MED25 leads to activation of a p21 reporter, this raises the possibility that MED25 is involved in cell cycle control. An overlap has been discovered by comparison of MED25 target genes and genes identified previously as target for the viral activator EBNA2. The close homology between the activation domains of EBNA2 and VP16 implies a common mechanism of transcriptional activation by these two viral proteins through MED25. The involvement of MED25 in gene activation by viral activators might indicate a role for this Mediator subunit in viral transcription.
Abstract: Bovine chromaffin secretory vesicle ghosts loaded with Na+ were found to take up Ca2+ when incubated in K+ media or in sucrose media containing micromolar concentrations of free Ca2+. Li+- or choline+loaded ghosts did not take up Ca2+. The Ca2+ accumulated by Na+-loaded ghosts could be released by the Ca2+ ionophore A23187, but not by EGTA. Ca2+ uptake was inhibited by external Sr2+, Na +, Li +, or choline +. All the 45Ca2+ accumulated by Na+-dependent Ca2+ uptake could be released by external Na +, indicating that both Ca2+ influx and efflux occur in a Na+-dependent manner. Na + -dependent Ca2+ uptake and release were only slightly inhibited by Mg2+. In the presence of the Na+ ionophore Monensin the Ca2+ uptake by Na +-loaded ghosts was reduced. Ca2+ sequestered by the Na+-dependent mechanism could also be released by external Ca2+ or Sr2+ but not by Mg2+, indicating the presence of a Ca2+/Ca2+ exchange activity in secretory membrane vesicles. This Ca2+/Ca2+ exchange system is inhibited by Mg2+, but not by Sr2+. The Na + -dependent Ca2+ uptake system in the presence of Mg2+ is a saturable process with an apparent Km of 0.28 μM and a Vmax= 14.5 nmol min−1 mg protein−1. Ruthenium red inhibited neither the Na+/Ca2+ nor the Ca2+/Ca2+ exchange, even at high concentrations.
Purified secretory vesicles isolated from bovine neurohypophyses were found to take up Ca2+ when incubated at 30°C in media containing 10−7 to 10−4 M free Ca2+. At 10−4 free Ca2+ 19 nmol/mg protein were taken up within 30 min. The initial uptake at this Ca2+ concentration was about 2 nmol/mg protein per min. The uptake of Ca2+ to secretory vesicles was not affected by ATP, oligomycin, ruthenium red, trifluoperazine, Mg2+ or K+, but was inhibited by Na+ and Sr2+. From these characteristics it can be concluded that the uptake system does not utilize directly ATP (as the Ca2+-ATPases known to be present in the cell membrane and the endoplasmic reticulum) and is different from the mitochondrial Ca2+ uptake system driven by respiration and/or ATP hydrolysis. However, Ca2+-Na+ exchange may well operate: In experiments using different concentrations of Na+ we found half-maximal inhibition of Ca2+ uptake with 33.3 mM Na+. An analysis of the data in a Hill plot indicated that at least 2 Na+ would be exchanged for 1 Ca2+. Also, it was found that Ca2+ previously taken up could be released again by external Na+ but not by K+.
Intact secretory vesicles isolated from bovine adrenal medulla contain 94 nmol Na+ per mg of protein, and Ca2+ influx into the vesicles is inhibited by increasing concentrations of extravesicular Na+ (but not of K+, Li+ or choline+) or by addition of the Na+ ionophore monensin. Thus Ca2+ influx is determined by the Na+ gradient across the vesicular membrane. Half maximal inhibition of Ca2+ influx occurs with 34 mM Na+ extravesicularly. The fact that Ca2+ can also be released from the vesicles by inversion of the Na+ gradient provides direct evidence that an Na+-Ca2+ exchange may operate. According to an analysis of the inhibition of Ca2+ uptake by Na+ in a Hill plot 2 Na+ would be exchanged for 1 Ca2+. Ca2+ influx into the vesicles increases with temperature (energy of activation: 16 kcal/mol), can be observed already with 10−7 M free Ca2+ and increases up to 10−4 M Ca2+. Ca2+ influx is not affected by Mg2+ but Sr2+ is inhibitory. Since the process is only slightly influenced by the pH of the incubation medium and is insensitive to Mg2+-ATP or inhibitors of the proton translocating Mg2+-ATPase the electrochemical proton gradient across the vesicular membrane does not affect directly the Ca2+ influx into the secretory vesicles. Ca2+ uptake is insensitive to ruthenium red and oligomycin.
Secretory vesicles isolated from rat liver were found to fuse after exposure to Ca2+. Vescle fusion is characterized by the occurrence of twinned vesicles with a continuous cleavage plane between two vesicles in freeze-fracture electron microscopy. The number of fused vesicles increases with increasing Ca2+-concentrations and is half maximal around 10–6 m. Other divalent cations (Ba2+, Sr2+, and Mg2+) were ineffective. Mg2+ inhibits Ca2+-induced fusion. Therefore, the fusion of secretory vesiclesin vitro is Ca2+ specific and exhibits properties similar to the exocytotic process of various secretory cells. Various substances affecting secretionin vivo (microtubular inhibitors, local anethetics, ionophores) were tested for their effect on membrane fusion in our system. The fusion of isolated secretory vesicles from liver was found to differ from that of pure phospholipid membranes in its temperature dependence, in its much lower requirement for Ca2+, and in its Ca2+-specificity. Chemical and enzymatic modifications of the vesicle membrane indicate that glycoproteins may account for these differences.
Fusion of plasma membranes isolated from myoblasts grown in culture has been investigated. 1. 1. Membrane fusion was specifically dependent on Ca2+ at physiological concentrations. However, at higher concentrations of cations, fusion could be triggered not only by Ca2+, but by Mg2+ and Sr2+ as well. 2. 2. The amount of fusion was directly proportional to temperature. 3. 3. Fusion was found to depend on the state of maturation of the myoblast membranes. 4. 4. Experiments with chemically and enzymatically modified membranes and with membranes derived from myoblasts grown in the presence of inhibitors of protein biosynthesis suggest the participation of proteinaceous membrane components in the fusion mechanism.
Reconstructed by Cerberus, the SR2 isn't exactly the same as the SR1. We dig into the differences between the ships and how it functions in Mass Effect 2.Subscribe so you don't miss any Mass Effect Lorecast Podcast episodes, lore, and other Mass Effect content from Robots Radio!Support us on Patreon! https://patreon.com/masseffectlorecastJoin us LIVE Sunday 10:30pm EST / 7:30pm PST: https://twitch.tv/robotsradioDiscord: https://discord.gg/JXKfVhMTwitter: twitter.com/masseffectcastEmail: masseffectlorecast@gmail.comMusic:Screen Saver by Kevin MacLeodLink: https://incompetech.filmmusic.io/song/5715-screen-saverLicense: https://filmmusic.io/standard-licenseROBOTSRADIO.netAdvertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy