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Are Cardinals Rare? What about Red Cardinals?
Inside: This article answers the questions "are cardinals rare?" and "are red cardinals rare?". You'll learn where you can expect to see them throughout North America and a sneak peek into cardinals that are REALLY rare.
I've been backyard birding for over 20 years and have seen hundreds of cardinals in my Wisconsin yard over that time. Many cardinals make Wisconsin their home, but what about in your neck of the woods? Are cardinals rare where you live?
I dove deep into the research and have the answer for you in this article.
Are Cardinals Rare?
Are Cardinal Endangered?
Differentiating between Endangered Species and Rare Species
When a Species is Endangered
When Species are Rare
Cracking the Myth: Red Cardinals are NOT Rare.
Discovering the Actual Rare Cardinals
Half-Male/Half-Female Cardinals
Yellow Cardinals
White Cardinals
Many people throughout the US and Canada have seen beautiful, vibrant red birds fly past or chirp in a nearby tree. This symbol of uplifting joy is a cardinal – northern cardinal to be more precise.
If you have seldom seen this lively bird singing away melodious songs, it is natural for you to think questions like "are cardinals rare?" or "are red cardinals endangered?."
Are cardinals rare? Are "red" cardinals rare?
No. Cardinals are not rare. Neither the red cardinal nor his buffy-brown mate is rare. There are more than 120 million breeding cardinals today and the number is steadily increasing. If you live within the range they live you have a good chance of spotting one.
Naturally, when asking if a bird species is rare the next logical question is are they endangered?. So, are cardinals endangered?
No. Cardinals are not endangered. They're plentiful in the Southeastern US and have been expanding their range north into Canada for decades now.
OK, so cardinals aren't rare and they're not endangered. But what does that mean? If you consider there are species that are rare but not endangered and vice versa, it's an interesting question. Let's take a look at the difference between being rare and endangered.
It is very common for people to confuse the two terms "endangered" and "rare," using them interchangeably. However, this is incorrect. It is essential to use these terms correctly, as they have quite different meanings.
"Endangered" refers to a specific species being in danger of extinction throughout their entire geographical range.
This means that this species is not found in large numbers in any region around the world. It also includes those that do exist but are not at their optimal health and are not actively breeding in large numbers and are at risk of possible extinction.
There are a lot of reasons as to why species can be endangered, ranging from habitat loss, habitat degradation, and invasive behavior to regular capture for animal trade and even climate change.
In contrast, "rare" is a colloquial term that has a broader meaning, with no specific definition outlined. It could mean that the species under observation has a minimal geographic range and is not common to spot in particular areas.
For example, cardinals can be considered rare in the northwest region of the United States due to the climate.
Northern cardinals live primarily in the US east of the Great Plains and parts of Mexico. They spend all of their time, including breeding, in the same general area.
According to The North American Breeding Bird Survey, there are about 120 million breeding cardinals today, a number that has constantly increased since the late 1960s; answering questions like 'are cardinals endangered?' or 'are cardinals rare?", become a very easy no.
Wondering where and how you can spot this magnificent medium-sized bird in the United States? I broke it down for you in the table below followed by a map for those of us who are more visual.
The Northeast Due to their adaptation to the chilly weather, as the name suggests, northern cardinals are concentrated heavily in the northeast. You should expect to see many in states like New York, Pennsylvania, Massachusetts, and Connecticut.
The Southeast With no aversion to heat and humidity, you'll commonly spot cardinals in states like Florida and Delaware, Tennessee, Virginia, and Louisiana.
The Midwest These red songbirds are found in abundance in the Midwest, especially in Illinois, Indiana, Iowa, Wisconsin, and Ohio. However, their enthusiasm for chirping in North and South Dakota is not the same.
The Southwest A large population of cardinals can be found in Texas and Oklahoma. Parts of southern Arizona can also expect to see cardinals. However, you will rarely spot them in the northwest region.
Northern cardinal range map. Compliments of The Cornell Lab of Ornithology.
The male northern cardinal is known for its vibrant red plumage while his lady is a buffy-brown. Many people don't realize they're a pair – from the same species. This may account for curiosity around its rareness. It makes sense. If you think all cardinals are red then you're only seeing 1/2 of the cardinals in your area.
Both male and female cardinals are easy to spot on trees due to their vivid feathers. In fact, unlike other wild birds, it is quite easy to tell between the two cardinal genders just by looking at their appearance.
Male cardinals are distinguishable by their beautiful red plumage. They are covered in bright red plumage from head to tail. Moreover, they have black spotting around their eyes and beak with a relatively more prominent crest on top of their heads.
Unique color attributes of the female cardinal compared to the male cardinal.
In comparison, female cardinals have a more faded reddish-brown plumage that blends into peach undertones.
Would You Like More Cardinals to Visit Your Yard?
You can start by making sure your yard is inviting and friendly for cardinals. Download my FREE guide & checklist How to Create a Cardinal-Friendly Yard and you'll have families of cardinals coming to visit year-round.
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For all the bird enthusiasts skimming through this article to look for something exclusive about cardinals, you're in for a surprise! While the answer to "are red cardinals rare?" will always be a no, you'd be hard-pressed to find a half-male and half-female cardinal! Yes, you read that right.
Half-Male/Half-Female Cardinal scientifically known as a cardinal with Bilateral Gynandromorphism. Photo by Jamie Hill.
A half-male and half-female cardinal has been spotted around Pennsylvania quite a few times and is scientifically described as having a genetic condition called Bilateral Gynandromorphism.
In appearance, this rare mutation makes it look like two cardinal birds of the opposite genders are morphed together into one.
Yellow northern cardinal. Photo by Erika Norris Church.
The fascinating mutations don't just stop there! Recently, a cardinal with a vivid yellow plumage has been spotted in Illinois. Yellow cardinals are unable to grow red feathers and are dubbed to be quite rare.
Leucistic northern cardinal. Photo by Bethany Knox.
If those 2 rare cardinals didn't get your attention – how about the white cardinal? This rare species comes in two flavors – albino and leucistic.
Albino cardinals are all white, have pink eyes, and are extremely rare.
Leucistic cardinals reflect a variation in how much of the body is white and how much is normal color (red for males, buffy brown for females).
Both white types of cardinals are a result of genetic mutations pertaining to a pigment necessary for producing red feathers.
If you've gotten to this point and realize the bird you're interested in is not a cardinal, rather it's a bird that looks like a cardinal, check out my article 9 Birds that Look Like Cardinals but Are Not to quickly identify your bird.
Cardinals are not rare – not even the red ones. Both male and female cardinals are found in abundance throughout the range they inhabit in the US and Canada and increase in numbers every year.
That said, there are several types of cardinals that truly are rare – the half-male/half-female cardinal, yellow cardinal, and white cardinal. As a result of a genetic or pigment issue, the rare cardinals fail to grow their feathers the correct color (red for males, brown for females).
Regardless of the type of cardinal you encounter, it's always fascinating to see them singing, chirping, and hanging out on our feeders.
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package engine

import (
	"fmt"

	"github.com/NetSys/quilt/cluster/provider"
	"github.com/NetSys/quilt/db"
	"github.com/NetSys/quilt/join"
	"github.com/NetSys/quilt/stitch"
	"github.com/NetSys/quilt/util"

	log "github.com/Sirupsen/logrus"
)

var myIP = util.MyIP
var defaultDiskSize = 32

// UpdatePolicy executes transactions on 'conn' to make it reflect a new policy,
// 'stitch'.
func UpdatePolicy(conn db.Conn, stitch stitch.Stitch) error {
	txn := func(db db.Database) error {
		return updateTxn(db, stitch)
	}

	if err := conn.Transact(txn); err != nil {
		return err
	}

	return nil
}

func updateTxn(view db.Database, stitch stitch.Stitch) error {
	err := clusterTxn(view, stitch)
	if err != nil {
		return err
	}

	if err = machineTxn(view, stitch); err != nil {
		return err
	}

	return nil
}

func clusterTxn(view db.Database, stitch stitch.Stitch) error {
	namespace := stitch.QueryNamespace()
	if namespace == "" {
		namespace = "default-namespace"
		msg := "policy did not specify 'Namespace', defaulting to '%s'"
		log.Warn(fmt.Sprintf(msg, namespace))
	}

	cluster, err := view.GetCluster()
	if err != nil {
		cluster = view.InsertCluster()
	}

	cluster.Namespace = namespace
	cluster.Spec = stitch.String()
	cluster.AdminACLs = resolveACLs(stitch.QueryAdminACL())
	view.Commit(cluster)
	return nil
}

// toDBMachine converts machines specified in the Stitch into db.Machines that can
// be compared against what's already in the db.
// Specifically, it sets the role of the db.Machine, the size (which may depend
// on RAM and CPU constraints), and the provider.
// Additionally, it skips machines with invalid roles, sizes or providers.
func toDBMachine(machines []stitch.Machine, maxPrice float64) []db.Machine {
	var hasMaster, hasWorker bool
	var dbMachines []db.Machine
	for _, stitchm := range machines {
		var m db.Machine

		role, err := db.ParseRole(stitchm.Role)
		if err != nil {
			log.WithError(err).Error("Error parsing role.")
			continue
		}
		m.Role = role

		hasMaster = hasMaster || role == db.Master
		hasWorker = hasWorker || role == db.Worker

		p, err := db.ParseProvider(stitchm.Provider)
		if err != nil {
			log.WithError(err).Error("Error parsing provider.")
			continue
		}
		m.Provider = p
		m.Size = stitchm.Size

		if m.Size == "" {
			providerInst := provider.New(p)
			m.Size = providerInst.ChooseSize(
				stitchm.RAM, stitchm.CPU, maxPrice)
			if m.Size == "" {
				log.Errorf("No valid size for %v, skipping.", m)
				continue
			}
		}

		m.DiskSize = stitchm.DiskSize
		if m.DiskSize == 0 {
			m.DiskSize = defaultDiskSize
		}

		m.SSHKeys = stitchm.SSHKeys
		m.Region = stitchm.Region
		dbMachines = append(dbMachines, provider.DefaultRegion(m))
	}

	if hasMaster && !hasWorker {
		log.Warning("A Master was specified but no workers.")
		return nil
	} else if hasWorker && !hasMaster {
		log.Warning("A Worker was specified but no masters.")
		return nil
	}

	return dbMachines
}

func machineTxn(view db.Database, stitch stitch.Stitch) error {
	// XXX: How best to deal with machines that don't specify enough information?
	maxPrice := stitch.QueryMaxPrice()
	stitchMachines := toDBMachine(stitch.QueryMachines(), maxPrice)

	dbMachines := view.SelectFromMachine(nil)

	scoreFun := func(left, right interface{}) int {
		stitchMachine := left.(db.Machine)
		dbMachine := right.(db.Machine)

		switch {
		case dbMachine.Provider != stitchMachine.Provider:
			return -1
		case dbMachine.Region != stitchMachine.Region:
			return -1
		case dbMachine.Size != "" && stitchMachine.Size != dbMachine.Size:
			return -1
		case dbMachine.Role != db.None && dbMachine.Role != stitchMachine.Role:
			return -1
		case dbMachine.DiskSize != stitchMachine.DiskSize:
			return -1
		case dbMachine.PrivateIP == "":
			return 2
		case dbMachine.PublicIP == "":
			return 1
		default:
			return 0
		}
	}

	pairs, bootList, terminateList := join.Join(stitchMachines, dbMachines, scoreFun)

	for _, toTerminate := range terminateList {
		toTerminate := toTerminate.(db.Machine)
		view.Remove(toTerminate)
	}

	for _, bootSet := range bootList {
		bootSet := bootSet.(db.Machine)

		pairs = append(pairs, join.Pair{L: bootSet, R: view.InsertMachine()})
	}

	for _, pair := range pairs {
		stitchMachine := pair.L.(db.Machine)
		dbMachine := pair.R.(db.Machine)

		dbMachine.Role = stitchMachine.Role
		dbMachine.Size = stitchMachine.Size
		dbMachine.DiskSize = stitchMachine.DiskSize
		dbMachine.Provider = stitchMachine.Provider
		dbMachine.Region = stitchMachine.Region
		dbMachine.SSHKeys = stitchMachine.SSHKeys
		view.Commit(dbMachine)
	}

	return nil
}

func resolveACLs(acls []string) []string {
	var result []string
	for _, acl := range acls {
		if acl == "local" {
			ip, err := myIP()
			if err != nil {
				log.WithError(err).Warn("Failed to get IP address.")
				continue
			}
			acl = ip + "/32"
		}
		result = append(result, acl)
	}

	return result
}


1 cup up tofu sour cream (optional) it tastes fine without!
Saute onion and garlic in a tbsp. of olive oil over medium heat, add cubed boca burgers until everything is browned. Stir in flour and other ingredients (except sour cream). When the sauce starts to thicken, take off from heat. Pour mixture into a medium sized casserole dish with a cover and bake for 30 mins at 325 degrees. Add the sour cream and enjoy over mashed potatoes, noodles, or rice!
I had some leftover homemade mushroom and onion gravy so I used that instead of soup, used tvp instead of the boca burgers and forgot to add the flour. It was delicious!
I substituted gardein homestyle beefless tips for the boca burgers; a packet of onion mushroom soup mix + 2 cups water for the can of french onion soup; soy sauce instead of the worcestershire sauce;used 8 ounces of sliced mushrooms; had to add bit extra flour to thicken it; and i cooked it on the stove top instead of baking; added sour cream @ the end and heated it thru.
This is a wonderful recipe. Thanks for sharing it. I'm not vegan but I adjusted things and it was every bit as good as the other reviewers say it was. I used GimmeLean "beef".
Our family is new to vegetarian... and this was our first recipe off the site.
We made this last week with the boca burgers (we like the these) and my whole family LOVED it. I am actually getting ready yo make it again.
I made this the other night...yummy! I used Morning Star's beef strips (vegan) in place of the burger bits. I also used Bragg's Amino liquid -I didn't have Worchestire sauce on hand. My husband raved about how tasty it was. Thanks!


text:
Why Ethical Procurement Matters
Traditionally, the primary goal of most businesses was simply to turn a profit. But companies, like the people who staff them, do not operate within a void, and as the world as grown more interconnected, every business decision can have powerful and lasting ramifications. It is unsurprising to find, then, that ethical procurement—the practice of balancing return on investment (ROI) against the potential impact that purchasing goods and services has on a company's supply chain, reputation, and sociopolitical/environmental footprint—has become a driving force for companies seeking ROI in a responsible way.
The value of ethical procurement lies in both tangible and intangible gains for a company. In order to ensure your company maximizes both, it's essential to understand what ethical procurement is and how you can make it part of your best practices within the procurement process.
The Importance of Ethical Procurement
In an ideal world, ethical procurement would be the default state of affairs for businesses of all sizes and types; doing the right thing for the company and the right thing for the society the company operates within would be the same. Which is not to say that ethics and morality are the same thing, of course, but rather that what is ethical is what is just, fair, and consistent with the values one champions.
But as procurement professionals in the real world know, even the sturdiest code of ethics can be severely tested in a world where not everyone is on the side of the light with regard to conflict of interests, human rights, child labour, and other unethical behavior.
For companies, the question of ethical procurement boils down to supply chain management blended with meeting legal, moral, and societal obligations and expectations. These obligations and expectations are contextual, as different societies have different views on the importance of personal gain in partnership with corporate profits, or the definition of a term like "corruption."
Regardless of location, however, ethical procurement always requires an understanding of a company's social responsibility in addition to its legal one—and an intelligent approach to eliminating unethical practices from its procurement activities. A bribery scandal might create hefty fines, for example, but the lasting damage to a company's reputation could bring it to its knees if it loses the trust (and therefore the business) of its customer base.
Trust lies at the crux of ethical procurement. Losing it not only damages customer relations and public perception, but supplier relationships and the efficacy of procurement activities themselves. A company known for unethical behavior may have trouble attracting new potential suppliers, or earning incentives, discounts, and "extra-mile" customer support from existing ones. They may also attract the wrong sort of suppliers, whose own unethical practices could spell further disaster.
These companies may find themselves under extra scrutiny from government compliance teams, or denied crucial funding by wary financial institutions. Companies that use suppliers who shirk the law, using child labour, disregarding basic human rights, or violating environmental compliance mandates may find themselves excluded from lucrative government bids. And if the public finds a company's practices questionable, it can lose millions to boycotts and bad press.
"Trust lies at the crux of ethical procurement. Losing it not only damages customer relations and public perception, but supplier relationships and the efficacy of procurement activities themselves."
Ethical Procurement Challenges
For procurement teams, identifying the types of ethical issues a company is likely to face is the first step in developing ethical standards for better business practices. Modern supply chains are global, complex, increasingly managed with the help of both automation and artificial intelligence, and rife with potential ethics violations. Consider these examples:
Bribery: The oldest form of greasing the wheels. Quid pro quo, special considerations or support for specific candidates during supplier evaluation or contract negotiation, or good old fashioned kickbacks are just a few examples.
Coercion/Intimidation: When threats of loss and harm are offered instead of cash or kickbacks. May occur in tandem with bribery.
Extortion: On the other side of the bribery mirror lies requests for money in exchange for consideration or to prevent exposure of other corruption. May occur alongside coercion and other unethical behavior, including threats of violence.
Nepotism: Giving unearned advantage or preference to suppliers who are family or friends.
Illegal Supply Chain Practices: Purchasing (knowingly or unknowingly) products produced via illegal or immoral means. Covers stolen goods and items produced using child labour (or modern slavery), human rights abuses, and environmentally irresponsible production, as well as counterfeit goods.
Influence Peddling: The practice of granting contracts (or speaking in support of granting contracts) to a specific supplier in exchange for discounts, special incentives, or other compensation by the party receiving the contract.
These violations, and others like them, can occur at any stage within the procurement function, on both sides of the supply chain, and may even extend to the C-Suite if left unchecked. Fallen corporations such as Enron, Worldcom, and others provide powerful case studies for the heavy price of unethical behavior, for both the perpetrators and the lives of countless others.
Implementing Ethical Procurement Practices
A code of ethics can be as comprehensive and complex as a novel-sized manual (such as the one issued by the United Nations) or as simple as a Web page outlining a company's code of conduct and commitment to socially, environmentally, and legally compliant procurement ethics.
The best code of ethics is one that reduces your risk of loss and supports business goals while maximizing your compliance with societal and legal demands. You can develop an ethical procurement process by following some basic best practices.
Evaluate Potential Ethics Issues in Your Supply Chain
Begin with an in-depth review of your entire supply chain, both direct and indirect, to identify risk exposure created by illegal and unethical practices. Don't overlook ancillary practices outside a supplier's core business; an ostensibly "squeaky clean" supplier may use illegal employment practices in hiring support and cleaning staff, for example, or support human rights abuses in purchasing materials or goods from a third party that violates child labour laws.
Review Your Procurement Team and Existing Ethical Practices
An internal audit of your existing practices and any "special relationships" between staff and vendors will help you identify and eliminate conflict of interests and other violations of your procurement policies and ethical standards.
Prioritize and Streamline
Once you've evaluated your chain and procurement function and identified the specific supply management issues and internal practices leading to ethics violations, prioritize the most dangerous and costly, and begin developing a plan to eliminate them. Connect with others in your industry who are facing the same challenges, or hire ethics consultants to assist in determining your best path forward.
In addition, introducing automation and artificial intelligence to your workflows through implementation of a cloud-based, centralized procure-to-pay system can also help. Automated workflows with built-in contingencies and three-way matching, combined with integrated supply chain management and intelligent data management, creates a procurement environment where risk-creating theft, rogue spend, and fraud cannot thrive.
Develop and Implement an Ethical Procurement Strategy
In order for ethical standards to succeed, they need support from a formalized, written ethics policy that clearly and completely describes the obligations and expectations imposed upon staff, suppliers, and senior management.
Ideally, your ethical procurement strategy will include:
Clear, precise language.
Availability both online and off.
Initial training for all procurement team staff as well as the organization as a whole, with scheduled refreshers as necessary.
Information on resources available for further clarification, support for suspected ethics issues, etc.
Explicit guidelines where required, e.g. maximum dollar values for gifts (if permitted), procedures implemented to avoid undue overlap of staff responsibilities, limits on familial or social relationships between buyers and suppliers, etc.
Additional context for supply chain management concerns such as sustainable sourcing, limits or bans on suppliers and materials from certain areas of the country or planet, and human rights, financial, or other legal issues that may affect a given supplier's eligibility to bid for contracts.
Full-buy-in from senior management and enthusiastic, vocal support for all ethics standards.
Mechanisms in place to ensure frequent reviews and refinements as events warrant (e.g., changing laws, changes in public support for certain issues, etc.)
Ethical Procurement is the Key to a Responsible ROI
Doing the right thing can be hard for companies as it is for individuals. But by embracing ethical procurement, your company can protect and enhance its profits, public image, and productivity while also pursuing profitability and innovation—and protecting itself from unnecessary risk, expense, and scandal.
Make Ethical Procurement Your Policy, Enforce It With PurchaseControl's Vendor Management

redpajama_set_name: RedPajamaCommonCrawl


Cabot Energy Plc (LON:CAB) has shown that its Canadian business has had a "seriously good kick-start", according to WH Ireland analyst Brendan Long, who reckons the relaunched group will be turning heads in Calgary.
In a statement, on Thursday, Cabot told investors it has been producing some 550 barrels of oil per day, which is in line with guidance, and its summer programme is set to expand on that significantly.
The company, previously known as Northern Petroleum, expects the new work programme to target an additional 300 bopd. It will include two side-tracks from existing wells, plus recompletion of two previously drilled wells and work-overs to three other wells.
It is budgeted to cost some US$3.5mln, and sets the newly relaunched group up for a year-end production target between 800 and 1,000 bopd.
WH Ireland's Brendan Long, in a note, said: "1,000 b/d is a key milestone and although it is an ambitious target and the high-end of the range, shareholders should take note that Cabot is aiming high, moving fast and delivering.
"Most importantly is the capex side of the equation – the returns on these modest investments tells the real story of how Cabot has emerged as a successful high-growth oil company with material production.
"They have hardly used any capital. We are unsure for how long this model will last because it is unusual for such gains to be realised in a mature/safe petroleum province, time will tell.
Long added: "So much for an AIM company not being able beat the locals at their own game, or has Cabot gone local?
Chief executive Keith Bush, in a statement, said: "I am very pleased to see the growing levels of production from Canada following the successful completion of the work programme from the first half of the year.


text:
La terza e ultima stagione della serie televisiva Control Z è stata interamente distribuita per la prima volta sulla piattaforma Netflix il 6 luglio 2022.

Control Z

redpajama_set_name: RedPajamaWikipedia


The Junior Market Lamb Show was initiated at the Arizona National Livestock Show in 1977, and continues to remain competitive.
Through their involvement in raising a lamb, exhibitors are able to consider multiple careers and occupations, learn expected workplace behavior, develop specific skills within an industry, and are given opportunities to apply academic and occupational skills. Through these strategies, exhibitors learn how to apply what they are learning in the classroom in preparation to transition into the world of college and career opportunities.
Market lambs are judged on the amount of muscling in their hind legs; the length, width and thickness of the loin; structural correctness; volume and capacity; style and balance.
Exhibitors competing in the Market Lamb Show must own a lamb by October 31. The lamb will be approximately 10 months old when sold at the Junior Market Auction. The Grand Champion Market Lamb is selected from division weight group champions.


Weekly Sales Activity Report – If it involves you wanting to establish aims for yourself that there are plenty of methods this can be accomplished. You could ofcourse only think about setting them. However if you truly need to be certain that you achieve your goals then using goal setting worksheets needs to be considered.
Excel can be an accountant's software. What application can we use a lot more? We've our overall ledger apps, ERP apps, e mail, phrase, etc.. As for me personally and the majority of other attorneys, Excel is your most used tool we have.
Be certain you stay up to date with all the changes which have happened. If the company you benefit doesn't use the brand new Excel, go get it on your personal use. I'm hearing an increasing number of tales about candidates being requested in job interviews with this matter: Exactly what version of Excel does your company use? When the candidate states 2003, the interviewer cites that this program has changed a lot at the brand new 2007 launch, also implies the candidate has been out-of-date using the tools he's using.
Now the moment it comes to finding objective worksheets you'll find many places on the web where these may be seen. You might always choose a basic listing of worksheets many that can be obtainable for free, but may well not really assist you to track and focus your ends. For that reason if you truly want to see the correct types of results then selecting more comprehensive goal systems should be contemplated.
However take note that initially employing those objective worksheets can establish a struggle. It should require work from your end to place up these and to answer all of the questions but the further you use them the more you may understand them. The truth is many people who these worksheets over a normal basis have now found they have become second character. In reality a lot of folks love the practice of tracking how much they have achieved. That has led in their goal-setting taking a whole new significance and they are succeeding much more and much faster. This really is one of the essential benefits of carrying out a defined system. Regardless of what you want to achieve, it is strongly suggested that you simply begin with a fantastic goal setting worksheet and follow it through. You're going to be stunned at how effective just the easy task of answering exactly the goal setting questions is.
Related Posts of "Weekly Sales Activity Report"


Great Lakes region to ease restrictions on hunting Canadian Snow Geese.
season on record. In Michigan, new restrictions will start next year.
communities where the tradition of sturgeon spearing spans generations.
getting "back to nature" for what ails them. From chamomile tea to St.


I worked with some amazing Middlesex Residency alumni during medical school who quickly became my mentors and inspired me to pursue family medicine. After spending a month at Middlesex during 4th year, I knew this was the program where I would be challenged to grow both professionally and personally in a supportive and welcoming environment. I also knew I wanted to spend time during training learning more about integrative medicine and the individualized tracks allow that to happen.
I have a strong interest in nutrition, osteopathy, and acupuncture. I am planning to pursue the Integrative Medicine Track and hope to complete the Fellowship in Integrative Medicine from the University of Arizona.
Working out in our basement gym, doing yoga, cooking, weeding the garden, sitting on the porch, listening to podcasts, and spending time with my husband. I also love home improvement projects and am in the process of repainting every room in our house.
I used to work for the U.S. Forest Service and was trained as a wildland firefighter.


text:
A view of the crowd at the Sarojini Nagar Market, in New Delhi on January 10, 2022. (Qamar Sibtain/IANS)
Private offices in Delhi told to switch to 'work from home' as COVID cases rise
11 Jan, 2022, 7:57 am
New Delhi, January 11, 2022
All private offices in Delhi have been mandated to ask their employees to work from home in view of the surge in COVID-19 cases in the past few days.
The decision came after a meeting of the Delhi Disaster Management Authority (DDMA) chaired by Lt Governor Anil Baijal here yesterday to review the COVID-19 situation in the national capital.
The meeting noted that the numbers of COVID-19 cases, including those of the new and more transmissible variant Omicron, were rapidly increasing and the positivity rate had crossed 23%.
The eeting felt it was necessary to impose additional restrictions on the movement and gathering of people to contain the spread of the coronavirus.
"All private offices shall be closed, except those which are falling under the 'Exempted Category' as prescribed in DDMA's GRAP Order No. 460 dated 08.08.2021. The practice of work from home shall be followed," the order issued today said.
The meeting also decided that all restaurants and bars would be closed. However, restaurants would be allowed to function ony for home delivery or takeaway of food items.
Till now, offices had been asked to function with half their employees in office and the rest at home. Government offices in the national capital are already working with only 50 per cent capacity.
Delhi reported 19,166 new cases of COVID-19 infection and 17 deaths in the last 24 hours. It had added 22,751 cases and 17 deaths to the tally yesterday.
The number of active cases of COVID-19 in the national capital rose by 5,073 in the last 24 hours to 65,806.


When two moles of aldehyde is treated with sodium hydroxide, a reaction occurs in which one mole of aldehyde is oxidized (giving carboxylic acid) while the other mole of aldehyde is reduced (giving primary alcohol).
Cannizzaro reaction is disproportionation reaction in which two molecules of an aldehyde are reacted to produce a primary alcohol and a carboxylic acid using a hydroxide base. This is shown in the example of benzaldehyde which produces benzoic acid and benzyl alcohol. And disproportionation is a redox reaction in which a compound of intermediate oxidation state converts to two different compounds, one of higher and one of lower oxidation state.
In the first step, a hydroxide ion serves as a nucleophile to attack the carbonyl group of aldehyde. This is followed by deprotonation to give a dianion.
In the second step, the resulting intermediate then functions as a hydride reducing agent. This unstable intermediate releases a hydride anion which attacks another molecule of aldehyde. In this process, the dianion is converted to carboxylate anion and the aldehyde to an alkoxide anion.
And in the last step, the alkoxide picks up a proton from water to provide the alcohol final product. The alkoxide is more basic than water so this reaction can proceed. And the carboxylate anion is converted to the carboxylic acid product after acid workup. Because the carboxylate is less basic than water, thus cannot pick up a proton from water and requires an acid workup to protonate.
More useful is the crossed-Cannizzaro reaction in which two different aldehydes react. Usually, formaldehyde is reacted with another aldehyde. The formaldehyde reduces the aldehyde to alcohol and is itself oxidized to formic acid.


text:
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In this example, Alabama are the favorites and you must wager $450 dollars to turn a profit of $100.Good to hear from you.Flyers Second Power Play Unit in 2017 The team's second power play unit wasn't Prospect camps around the league will soon be underway, followed by training camp, preseason, and then game number one of the regular season on Oct.Brazil Brazil turned in their best performance of the tournament against Colombia, however it Rob Kelley Jersey came with a costly price.European World Cup Qualifier.
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text:
Q: How to get distinct columns clientid and code grouped together by latest date? I have the table as following:
clientid   code  band   date
49          1    2-59   1899.12.01
49          1    2-54   2004.11.01
49          1    0-54   2013.05.17
49          2    60-64  1899.12.01
49          2    55-59  2004.11.01
49          3    65-69  1899.12.01
49          3    60-64  2004.11.01

How can I get distinct (clientid and code) by latest date.
For example, after executing solution I have to get the following table:
clientid   code  band   date
49          1    0-54   2013.05.17
49          2   55-59   2004.11.01
49          3   60-64   2004.11.01

It is logical that I have to use MAX(date) and GROUP BY (clientid, code). This logic seems correct, but when I execute it it gives me an error that band is not included in GROUP BY. However, I cannot include band to GROUP BY because it is not going to sort correctly.
Following is the code that I have implemented so far.
SELECT clientid, code, band, MAX(date)
FROM tempTeble
GROUP BY clientid, code;

A: You can use a subquery that will be correlated with a main query.Try this:
SELECT clientid, code, band, date
FROM tempTable t
WHERE date = (
    SELECT MAX(date)
    FROM tempTable t2
    WHERE t2.clientid = t.clientid AND t2.code = t.code)

The subquery finds max date for every combination of clientid and code. The main query returns only these records for every combination of clientid and code for which date is equal to max date (that was found by the subquery).

A: My solution using common table expression
WITH cte as
(
SELECT clientid,code,MAX(date) AS date from tempTable
GROUP BY clientid,code
)
SELECT t.*
FROM cte c
INNER JOIN tempTable t
ON c.clientid=t.clientid
AND c.code=t.code
AND c.date=t.date

For variety,It can also be done using join
SELECT t1.*
FROM tempTable t1
JOIN (SELECT clientid,code,MAX(date) AS date from tempTable GROUP BY clientid,code) t2
ON t1.clientid=t2.clientid
AND t1.code=t2.code
AND t1.date=t2.date

redpajama_set_name: RedPajamaStackExchange


Patent lust red glitter lace-up sneaker trimmed with white leather. The sneaker features large flat laces and an oversized rubber sole. Finished with an Alexander McQueen signature on tongue and heel counter. Oversized rubber sole with a leopard stamp design. The sneakers come with an additional set of shoelaces.


Folks, today I have been married for five years.
The Holbs and I got married on a Tuesday afternoon in the Portland, Oregon Temple. We had our reception that night in a stable in Aloha.
The Holbs still has gloriously red hair. He is afraid of the spiders in Harry Potter and the Chamber of Secrets. He built me a patio this summer. He leaves his empty cereal boxes on the kitchen counter for me to throw away.
The Holbs cries at good movies. He plants trees and lilacs in the ground and worries for them in windstorms. He loves his dogs. He has a beautiful mouth and a dimple square in the middle of his chin. He has the greatest arm hair on the planet. He loves my goofy little brother.
Here's what have I learned in five years of marriage.
Men don't consider steamed vegetables to be a balanced meal.
Costco is a great place for a cheap date.
Praying as a couple, reading the scriptures together, and making it to church a little early somehow make your marriage so much stronger. But praying as a couple, reading scriptures together, and making it to church a little early somehow are somehow the hardest things in the world to do. I have no idea why that is.
Making babies can be a lot of fun. You should try it.
Happy Anniversary! I came across your blog. It's quite fun to read and to catch up on your life. My husband and I just celebrated #6. Time flies. Good luck with the baby stuff. It took us 15 months and fertility pills to do the trick. I hope you have quicker success than that! Have a great time celebrating!
grrrl, it happens to be the architect's and my anniversary today as well. eight years, baby. we're going to see batman. you and the ginger kid wanna come? here's what i know about marriage: good friends make it even better. thanks for being our good friends. congratulations around.
I am pretty sure Ryan is going to love your advice about farting during fights... Unfortunately, it will totally work on me too, because I am, at my core, incredibly immature.
Wow! 5 years! Hold on to your hat batman...we are going onto #12!!! Steve JUST took me to see X-files yesterday (& we had to take all 3 kids with us cause we couldn't find a sitter) & we had to wait for it to hit the $1 theater!!! And we did just finnish reading book #4 of the twilight series together! Nerds unite!!!
So awesome to find your blog.


Create your free blog with Blogger. Your blog is whatever How to install: Download and install Minecraft Forge. Download the mod. Go to %appdata%. Go to .minecraft/mods folder. If the "mods" folder does not exist 7 Days To Die мод на зомби апокалипсис для майнкрафт 1.7.10 добавит в игру не только кровожадных.
Кликабельная сводная таблица всех сетевых игр (и их режимы, количество игроков), доступных. Crafting Dead Mod is a Multiplayer based mod that puts you into a Zombie Apocalypse. Look for loot, craft base parts and fend off endless masses of zombies. Let's assume you're talking a walk along a road in your town/city/whatever. You see a large advertisment, advertising random stuff you would never be interested. Сервера майнкрафт 1.5.2. Мониторинг серверов майнкрафт 1.5.2 - топ русских серверов Minecraft 1.5.2. Выживание в Minecraft с модом Solar Apocalypse, серия 1, часть 1. minecraft выживание на острове часть.
You may use Cars and Drives in your mod pack as long as you. 1. Include me as the mod author 2. Provide a link to the forum post. 3. ! Call the mod 'Cars and Drives. Скачать Моды на Майнкрафт 1.6.4, а также Мод на Майнкрафт 1.11 для того чтобы играть в Minecraft.


← Part 46D Australia's "irrelevant" crimes against Humanity. 'Surfing' isn't just surfing and 'Burking' isn't just burking.
Did you know about the massive 'Poll Tax' on 1st preference voting?
As the Australian Electoral Commission data below reveals, we voters are paying a massive 'Poll Tax' when we give our 1st preference votes to the major political parties. Unless we demand that this tax on 1st Preference votes be scrapped immediately, the Federal election Poll tax will cost us round $3.5 – $4 BILLION by the end of the century!
In the 2013 and 2016 federal elections, we voters paid the Liberal-National Coalition, the Labour Party, and the Greens, the bulk of a staggering $120,854,731 for the so-called 'privilege' of giving these parties our 1st preference votes.
Again, these figures reveal that almost $6 in every $7 taxpayers' dollars were paid to the Liberal-National coalition and the Australian Labour Party.
In all, in the 2013 and 2016 federal elections, the Coalition and the Australian Labour Party received $98,426,866 of taxpayers' money out of a total 'prize pool' of $120,854,731 or 81.44%.
The winnings of the next major prize poll winner, the Australia Greens, i.e. $6,717,055.98 + $5,531,871.45, totals a very substantial $12,248,927.43 or 10.13% of the prize pool.
In all, in the 2013, and 2016 federal elections, the Liberal-National Coalition, the Australian Labour Party and the Australian Greens received a massive $110,775,793 of taxpayer's money , i.e. 91.57% of the 1st Preference Bonanza Lottery prize pool.
On the huge WHITE ballot paper, vote BELOW the line in every election, federal, state or territory.
If you want the Liberal-national Coalition, Labour or the Greens to win, give them your 2nd Preference vote.
Your 1st Preference vote should go to some one who is totally unknown, i.e. a 1st Timer INDEPENDENT candidate, or alternately, the person who has come either last or 2nd last in a previous election.
By giving your 1st preference vote to some one who will be unlikely to pick up the minimum 4% of 1st preference votes, that person receives no payments, i.e. no 'Poll Tax' on 1st Preference votes is paid.
Voting below the line on the WHITE ballot paper may give you between 30 – 150 candidates to pick from and if enough people vote below the line, your mainstream preferred candidate may win on 2nd or 3rd preferences, or even on 23rd preferences, but they loose out on the 1st Preference Poll Tax payments.
So, to reduce the Poll Tax on 1st preference votes, just don't give this vote to mainstream party candidates.
On Saturday 17th March 2018, when South Australians vote for new state government, in my electorate I have 4 mainstream candidates and 1 newcomer.
In next Saturday's election in South Australia, my 1st preference vote will go to the-new-kid-on-the-block, whilst my 2nd preference will go to the candidate that I hope wins the election.
In the Upper House – the big WHITE ballot paper, there are 22 mainstream (Liberal-National, ALP & Greens) candidates and 20 minor party and un-grouped Independent candidates vying for 11 seats.
By voting below the line, I can randomly give votes to 5 Independent or minor party candidates and the next 6 votes to the candidates that I want to win.
My preferred winners may be spread across the 4 mainstream parties with 1 each from the 2 minor parties, or visa versa.
The end result is that I vote as I want and not as the money grubbing mainstream parties want me to vote.
By having a diverse range of groups in the Upper house, no party dominates and extremist policies have little chance of being railroaded through the Upper House, regardless of who wins in the Lower House and forms government.
Vote smart and you not only reduce the massive, taxpayer funded, Poll Tax on 1st Preference "Above the Line" votes that funnels money in the coffers of political parties, you also deprive them of the ability to make stupid laws.
That is called a WIN-WIN result for voters.
This entry was posted in abuse of power, election, News and politics, Political, Uncategorized and tagged 1st preference, above the line, independent, mainstream parties, poll tax, vote below the line, vote smart. Bookmark the permalink.
I say put all these major party scumbags at the bottom of the paper, i.e. absolute last with the greens there too. All these elections are just a waste of time and money if the major party scumbags are not put last.


Workshops - "...a duo that is both a technical marvel and tastefully perfect"
EDUCATIONAL OUTREACH: Peter and Mary Danzig are both passionate educators and present a variety of engaging workshops and programs for children and adults. They both maintain private studios of students and have taught music in public and private schools. Peter is currently an instructor for Banjo and Songwriting for the University of Utah. He also spent several years working for the Utah Opera Company as a composer in residence for their educational outreach program where he traveled to schools to lead students in composing songs and musicals. Mary is a skilled teacher who has taught numerous workshops on traditional instruments, singing, and group instrument instruction.
Workshops include but are not limited to the subjects listed below. If you have a specific need not mentioned in this list it is likely we can design something to fit your needs.
INSTRUMENTAL: Not only are Peter and Mary award winning instrumentalists (2nd Place 2011 National Mandolin Championship, 2011/2012 Utah State Fiddle, Mandolin, and Banjo Champions) but they are also passionate about inspiring the next generation of players. Their classical training combined with their in depth knowledge of traditional American instruments and music allow them to offer a wide variety of educational workshops and presentations. Instructional workshops can be offered at any level on violin/viola, guitar (fingerstyle and flatpick), mandolin, banjo, and Appalachian dulcimer.
SONGWRITING/ARRANGING: Otter Creek is known for their innovative and exciting arrangements of both their traditional and original music. In addition, Peter is an award winning Songwriter (Winner: 2010 NewSongs Showcase, Walnut Valley Festival; Winner: 2011 Suzanne Millsaps Performing Songwriter Showcase) and has years of experience helping children and adults create their own songs.
SCHOOLS: (Assemblies and Workshops) With experience gained from their years in public and private education as well as Peter's experience as a child and adolescent therapist, Otter Creek is adept and engaging students of all ages.
IMPROVISATION, JAMMING, & PERFORMANCE: Otter Creek teaches workshops for students of all levels on improvisation and jamming skills and can include your choir (and possibly instrumental ensemble) in their performance while they are in town if it can be arranged.


it was last November when i posted my 1000th pageviews post. and now when it's only January when i posted my 5000th pageviews!
i also want to thank my followers and the many visitors who have spent their time visiting my blog.
as a form of thanks to all my visitors, i will be doing a Free Book Giveaway!
this Giveaway contest will open around mid-January.
@A.S Dewi: salam kenall :D terimakasih sudah jdi pembaca setiaa..


text:
ESPNESPN
Engine options leveling field, but some teams still behind
Jayski.com Staff
The soft open for the new NASCAR Camping World Truck Series spec engine has suddenly become a requirement, apparently, with every team working to obtain enough power plants to sustain a full fleet during the first couple of races this season.
When NASCAR first decided to introduce a spec option during the off-season, the understanding was that the sanctioning body would ease the engines into use so as not to alienate teams that wanted to retain manufacturer-supported engines. But after several tests, it appears that the Ilmor-produced NT1 is more competitive than the existing OEMs.
After winning the Cup Series pole on Friday, Kyle Busch said that's problematic, because Ilmor doesn't have enough inventory to meet the demand.
"We don't have enough Ilmors," Busch said. "They don't have enough to ship out to go around. So yeah, that's been awesome. We're kind of shorthanded on some of that stuff. All of our backups, if we had to go to a backup truck, has all of our OEM stuff in it.
"We just don't have enough engines right now. We were late to the game with ordering that stuff because we were trying to stick with the OEM."
To his point, all but 11 trucks have been entered with Ilmor NT1s this weekend at Atlanta Motor Speedway. The KBM No. 18 (Noah Gragson) and Hattori Racing Enterprises No. 16 (Brett Moffitt) are the only Toyotas with actual Toyota engines.
Fourth-year driver/owner Jordan Anderson says he couldn't have sold sponsors on a full-time schedule this season if not for the cheaper and more durable spec engine. He scored his first career top-10 last week at Daytona with the motor.
The Ilmors are expected to last 1,500 miles before a rebuild and could save teams hundreds of thousands of dollars in engine rebuilds or lease programs.
--- AutoWeek ---


text:
Illinois sues e-cig maker Juul for allegedly targeting minors
By Robert Channick
Juul products are displayed Dec. 20, 2018, at a smoke shop in New York. Juul has pulled fruit- and candy-flavored pods from retail and online stores, but it faces mounting pressure from health experts, state law enforcement officials and federal regulators over vaping's prevalence among youth. (Seth Wenig/AP)
The Illinois attorney general's office filed a consumer fraud lawsuit Thursday against Juul Labs, alleging the e-cigarette maker targets its product to minors and misrepresents the ability of its devices to help people quit smoking.
Citing epidemic levels of addiction to vaping tobacco products among underage users across the state, Attorney General Kwame Raoul announced the Illinois lawsuit as "one part of a multifaceted" effort to hold Juul accountable for undoing years of progress in reducing youth smoking rates.
The lawsuit against Juul comes amid mounting pressure from health experts, state law enforcement officials and federal regulators over vaping's prevalence among youth, where a recent government survey showed 1 in 4 high school students used e-cigarettes. Consumers must be over 18 to buy and use e-cigarettes.
In November, the attorneys general of New York and California filed similar lawsuits alleging the e-cigarette maker deliberately marketed its vaping products to teenagers.
The Illinois lawsuit, filed in Cook County Circuit Court, alleges Juul "had a central role in undoing years of work by government agencies and anti-tobacco activists in order to addict a whole new generation to nicotine." While cigarette smoking by high school teens dropped to 5% in 2017, from 36% in 1997, e-cigarette use continues to grow.
"In high schools, even middle schools, they are now referring to the restroom as the vaping room," Raoul said at a news conference announcing the lawsuit.
Vaping has contributed to a growing national health crisis, with thousands of cases of lung illnesses linked to vaping, mostly using products containing the psychoactive ingredient THC. Regulators are exploring everything from banning flavored e-cigarettes to halting sales entirely.
Illinois Department of Public Health Director Dr. Ngozi Ezik, who spoke at the news conference, said there have been 201 confirmed cases of vaping lung illnesses in Illinois, with the youngest patient 13 years old. There have been five vaping-related deaths in Illinois, Ezik said.
From the sleek e-cigarette device to sweet and fruity flavors masking a higher nicotine content, the product is attractive to youth smokers, the lawsuit says. In addition, the lawsuit alleges Juul was "deceptively marketing" its products to youth on social media.
"While we have not yet reviewed the complaint, we remain focused on resetting the vapor category in the U.S. and earning the trust of society by working cooperatively with attorneys general, regulators, public health officials, and other stakeholders to combat underage use and convert adult smokers from combustible cigarettes," Juul spokesman Austin Finan said in a statement.
Founded in 2007, San Francisco-based Juul is the dominant e-cigarette manufacturer, with a 75% share of the market, according to the lawsuit. Its system features a device loaded with flavored cartridges to deliver vaporized nicotine, which some argue is healthier than burning and inhaling tobacco smoke.
Juul has taken voluntary steps to tamp down usage among youth. Last year, it pulled fruit- and candy-flavored pods from retail stores and more recently, from its online store. In November, Juul said it would halt sales of its popular mint-flavored e-cigarettes, leaving only menthol and tobacco flavors. It also has suspended its advertising in the U.S., Finan said.
"Our customer base is the world's 1 billion adult smokers and we do not intend to attract underage users," Finan said.
The Illinois lawsuit also alleges that Juul misrepresents the ability of its devices to help people quit smoking, and that it has continued to market to that "different, but still vulnerable" group of consumers. Juul's products have not been approved by the U.S. Food and Drug Administration as a smoking cessation device.
"Far more new smokers are created by way of vaping than adult smokers quitting because of it," Raoul said at the news conference.
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text:
Kinase
Dihydroxyacetone kinase in complex with a non-hydrolyzable ATP analog (AMP-PNP). Coordinates from PDB ID:1UN9.[1]
In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the substrate gains a phosphate group and the high-energy ATP molecule donates a phosphate group. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group (producing a dephosphorylated substrate and the high energy molecule of ATP). These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis.[2][3][4] Kinases are part of the larger family of phosphotransferases. Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate groups to an acceptor, nor with phosphatases, which remove phosphate groups. The phosphorylation state of a molecule, whether it be a protein, lipid, or carbohydrate, can affect its activity, reactivity, and its ability to bind other molecules. Therefore, kinases are critical in metabolism, cell signalling, protein regulation, cellular transport, secretory processes, and many other cellular pathways, which makes them very important to human physiology.
Biochemistry and functional relevanceEdit
General reaction that is catalyzed by kinases.
Kinases mediate the transfer of a phosphate moiety from a high energy molecule (such as ATP) to their substrate molecule, as seen in the figure below. Kinases are needed to stabilize this reaction because the phosphoanhydride bond contains a high level of energy. Kinases properly orient their substrate and the phosphoryl group within their active sites, which increases the rate of the reaction. Additionally, they commonly use positively charged amino acid residues, which electrostatically stabilize the transition state by interacting with the negatively charged phosphate groups. Alternatively, some kinases utilize bound metal cofactors in their active sites to coordinate the phosphate groups. Protein kinases can be classed as catalytically active (canonical) or as pseudokinases, reflecting the evolutionary loss of one or more of the catalytic amino acids that position or hydrolyse ATP.[5] However, in terms of signalling outputs and disease relevance, both kinases and pseudokinases are important signalling modulators in human cells, making kinases very important drug targets.[6]
Kinases are used extensively to transmit signals and regulate complex processes in cells. Phosphorylation of molecules can enhance or inhibit their activity and modulate their ability to interact with other molecules. The addition and removal of phosphoryl groups provides the cell with a means of control because various kinases can respond to different conditions or signals. Mutations in kinases that lead to a loss-of-function or gain-of-function can cause cancer[7] and disease in humans, including certain types of leukemia and neuroblastomas, glioblastoma,[8] spinocerebellar ataxia (type 14), forms of agammaglobulinaemia, and many others.[9]
History and classificationEdit
The first protein to be recognized as catalyzing the phosphorylation of another protein using ATP was observed in 1954 by Gene Kennedy at which time he described a liver enzyme that catalyzed the phosphorylation of casein. In 1956, Edmond H. Fischer and Edwin G. Krebs discovered that the interconversion between phosphorylase a and phosphorylase b was mediated by phosophorylation and dephosphorylation.[10] The kinase that transferred a phosphoryl group to Phosphorylase b, converting it to Phosphorylase a, was named Phosphorylase Kinase. Years later, the first example of a kinase cascade was identified, whereby Protein Kinase A (PKA) phosphorylates Phosphorylase Kinase. At the same time, it was found that PKA inhibited glycogen synthase, which was the first example of a phosphorylation event that resulted in inhibition. In 1969, Lester Reed discovered that pyruvate dehydrogenase was inactivated by phosphorylation, and this discovery was the first clue that phosphorylation might serve as a means of regulation in other metabolic pathways besides glycogen metabolism. In the same year, Tom Langan discovered that PKA phosphorylates histone H1, which suggested phosphorylation might regulate nonenzymatic proteins. The 1970s included the discovery of calmodulin-dependent protein kinases and the finding that proteins can be phosphorylated on more than one amino acid residue. The 1990s may be described as the "decade of protein kinase cascades". During this time, the MAPK/ERK pathway, the JAK kinases (a family of protein tyrosine kinases), and the PIP3-dependent kinase cascade were discovered.[11]
Kinases are classified into broad groups by the substrate they act upon: protein kinases, lipid kinases, carbohydrate kinases. Kinases can be found in a variety of species, from bacteria to mold to worms to mammals.[12] More than five hundred different kinases have been identified in humans.[2] Their diversity and their role in signaling makes them an interesting object of study. Various other kinases act on small molecules such as lipids, carbohydrates, amino acids, and nucleotides, either for signaling or to prime them for metabolic pathways. Specific kinases are often named after their substrates. Protein kinases often have multiple substrates, and proteins can serve as substrates for more than one specific kinase. For this reason protein kinases are named based on what regulates their activity (i.e. Calmodulin-dependent protein kinases). Sometimes they are further subdivided into categories because there are several isoenzymatic forms. For example, type I and type II cyclic-AMP dependent protein kinases have identical catalytic subunits but different regulatory subunits that bind cyclic AMP.[13]
Protein kinasesEdit
Overview of signal transduction pathways. Many of the proteins involved are kinases, including protein kinases (such as MAPK and JAK) and lipid kinases (such as PI3K).
Main article: Protein Kinase
Protein kinases act on proteins, by phosphorylating them on their serine, threonine, tyrosine, or histidine residues. Phosphorylation can modify the function of a protein in many ways. It can increase or decrease a protein's activity, stabilize it or mark it for destruction, localize it within a specific cellular compartment, and it can initiate or disrupt its interaction with other proteins. The protein kinases make up the majority of all kinases and are widely studied.[14] These kinases, in conjunction with phosphatases, play a major role in protein and enzyme regulation as well as signalling in the cell.
A common point of confusion arises when thinking about the different ways a cell achieves biological regulation. There are countless examples of covalent modifications that cellular proteins can undergo; however, phosphorylation is one of the few reversible covalent modifications. This provided the rationale that phosphorylation of proteins is regulatory. The potential to regulate protein function is enormous given that there are many ways to covalently modify a protein in addition to regulation provided by allosteric control. In his Hopkins Memorial Lecture, Edwin Krebs asserted that allosteric control evolved to respond to signals arising from inside the cell whereas phosphorylation evolved to respond to signals outside of the cell. This idea is consistent with the fact that phosphorylation of proteins occurs much more frequently in eukaryotic cells in comparison to prokaryotic cells because the more complex cell type evolved to respond to a wider array of signals.[13]
Cyclin dependent kinasesEdit
Cyclin dependent kinases (CDKs) are a group of several different kinases involved in regulation of the cell cycle. They phosphorylate other proteins on their serine or threonine residues, but CDKs must first bind to a cyclin protein in order to be active.[15] Different combinations of specific CDKs and cyclins mark different parts of the cell cycle. Additionally, the phosphorylation state of CDKs is also critical to their activity, as they are subject to regulation by other kinases (such as CDK-activating kinase) and phosphatases (such as Cdc25).[16] Once the CDKs are active, they phosphorylate other proteins to change their activity, which leads to events necessary for the next stage of the cell cycle. While they are most known for their function in cell cycle control, CDKs also have roles in transcription, metabolism, and other cellular events.[17]
Because of their key role in the controlling cell division, mutations in CDKs are often found in cancerous cells. These mutations lead to uncontrolled growth of the cells, where they are rapidly going through the whole cell cycle repeatedly.[18] CDK mutations can be found in lymphomas, breast cancer, pancreatic tumors, and lung cancer. Therefore, inhibitors of CDK have been developed as treatments for some types of cancer.[18]
Mitogen-activated protein kinasesEdit
MAP kinases (MAPKs) are a family of serine/threonine kinases that respond to a variety of extracellular growth signals. For example, growth hormone, epidermal growth factor, platelet-derived growth factor, and insulin are all considered mitogenic stimuli that can engage the MAPK pathway. Activation of this pathway at the level of the receptor initiates a signaling cascade whereby the Ras GTPase exchanges GDP for GTP. Next, Ras activates Raf kinase (also known as MAPKKK), which activates MEK (MAPKK). MEK activates MAPK (also known as ERK), which can go on to regulate transcription and translation. Whereas RAF and MAPK are both serine/threonine kinases, MAPKK is a tyrosine/threonine kinase.
A variety of mitogenic signals engage the MAPK pathway and promote cell growth and differentiation through a kinase cascade.
MAPK can regulate transcription factors directly or indirectly. Its major transcriptional targets include ATF-2, Chop, c-Jun, c-Myc, DPC4, Elk-1, Ets1, Max, MEF2C, NFAT4, Sap1a, STATs, Tal, p53, CREB, and Myc. MAPK can also regulate translation by phosphorylating the S6 kinase in the large ribosomal subunit. It can also phosphorylate components in the upstream portion of the MAPK signalling cascade including Ras, Sos, and the EGF receptor itself.[19]
The carcinogenic potential of the MAPK pathway makes it clinically significant. It is implicated in cell processes that can lead to uncontrolled growth and subsequent tumor formation. Mutations within this pathway alter its regulatory effects on cell differentiation, proliferation, survival, and apoptosis, all of which are implicated in various forms of cancer.[19]
Lipid kinasesEdit
Lipid kinases phosphorylate lipids in the cell, both on the plasma membrane as well as on the membranes of the organelles. The addition of phosphate groups can change the reactivity and localization of the lipid and can be used in signal transmission.
Phosphatidylinositol kinasesEdit
Insulin binding to its receptor leads allows PI3 kinase to dock at the membrane where it can phosphorylate PI lipids
Phosphatidylinositol kinases phosphorylate phosphatidylinositol species, to create species such as phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), phosphatidylinositol 3,4,5-trisphosphate (PIP3), and phosphatidylinositol 3-phosphate (PI3P). The kinases include phosphoinositide 3-kinase (PI3K), phosphatidylinositol-4-phosphate 3-kinase, and phosphatidylinositol-4,5-bisphosphate 3-kinase. The phosphorylation state of phosphatidylinositol plays a major role in cellular signalling, such as in the insulin signalling pathway, and also has roles in endocytosis, exocytosis and other trafficking events.[20][21] Mutations in these kinases, such as PI3K, can lead to cancer or insulin resistance.[22]
The kinase enzymes increase the rate of the reactions by making the inositol hydroxyl group more nucleophilic, often using the side chain of an amino acid residue to act as a general base and deprotonate the hydroxyl, as seen in the mechanism below.[23] Here, a reaction between adenosine triphosphate (ATP) and phosphatidylinositol is coordinated. The end result is a phosphatidylinositol-3-phosphate as well as adenosine diphosphate (ADP). The enzymes can also help to properly orient the ATP molecule, as well as the inositol group, to make the reaction proceed faster. Metal ions are often coordinated for this purpose.[23]
Mechanism of phosphatidylinositol-3 kinase. ATP and phosphatidylinositol react to form phosphatidylinositol-3-phosphate and ADP, with the help of general base B.[23]
Sphingosine kinasesEdit
Sphingosine kinase (SK) is a lipid kinase that catalyzes the conversion of sphingosine to sphingosine-1-phosphate (S1P). Sphingolipids are ubiquitous membrane lipids. Upon activation, sphingosine kinase migrates from the cytosol to the plasma membrane where it transfers a γ phosphate (which is the last or terminal phosphate) from ATP or GTP to sphingosine. The S1P receptor is a GPCR receptor, so S1P has the ability to regulate G protein signaling. The resulting signal can activate intracellular effectors like ERKs, Rho GTPase, Rac GTPase, PLC, and AKT/P13K. It can also exert its effect on target molecules inside the cell. S1P has been shown to directly inhibit the histone deacetylase activity of HDACs. In contrast, the dephosphorylated sphingosine promotes cell apoptosis, and it is therefore critical to understand the regulation of SKs because of its role in determining cell fate. Past research shows that SKs may sustain cancer cell growth because they promote cellular-proliferation, and SK1 (a specific type of SK) is present at higher concentrations in certain types of cancers.
There are two kinases present in mammalian cells, SK1 and SK2. SK1 is more specific compared to SK2, and their expression patterns differ as well. SK1 is expressed in lung, spleen, and leukocyte cells, whereas SK2 is expressed in kidney and liver cells. The involvement of these two kinases in cell survival, proliferation, differentiation, and inflammation makes them viable candidates for chemotherapeutic therapies.[24]
Carbohydrate kinasesEdit
For many mammals, carbohydrates provide a large portion of the daily caloric requirement. To harvest energy from oligosaccharides, they must first be broken down into monosaccharides so they can enter metabolism. Kinases play an important role in almost all metabolic pathways. The figure on the left shows the second phase of glycolysis, which contains two important reactions catalyzed by kinases. The anhydride linkage in 1,3 bisphosphoglycerate is unstable and has a high energy. 1,3-bisphosphogylcerate kinase requires ADP to carry out its reaction yielding 3-phosphoglycerate and ATP. In the final step of glycolysis, pyruvate kinase transfers a phosphoryl group from phosphoenolpyruvate to ADP, generating ATP and pyruvate.
Hexokinase is the most common enzyme that makes use of glucose when it first enters the cell. It converts D-glucose to glucose-6-phosphate by transferring the gamma phosphate of an ATP to the C6 position. This is an important step in glycolysis because it traps glucose inside the cell due to the negative charge. In its dephosphorylated form, glucose can move back and forth across the membrane very easily.[25] Mutations in the hexokinase gene can lead to a hexokinase deficiency which can cause nonspherocytic hemolytic anemia.[26]
Phosphofructokinase, or PFK, catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate and is an important point in the regulation of glycolysis. High levels of ATP, H+, and citrate inhibit PFK. If citrate levels are high, it means that glycolysis is functioning at an optimal rate. High levels of AMP stimulate PFK. Tarui's disease, a glycogen storage disease that leads to exercise intolerance, is due to a mutation in the PFK gene that reduces its activity.[27]
Other kinasesEdit
The active site of riboflavin kinase bound to its products--FMN (on left) and ADP (on right). Coordinates from PDB ID: 1N07.[28]
Kinases act upon many other molecules besides proteins, lipids, and carbohydrates. There are many that act on nucleotides (DNA and RNA) including those involved in nucleotide interconverstion, such as nucleoside-phosphate kinases and nucleoside-diphosphate kinases.[29] Other small molecules that are substrates of kinases include creatine, phosphoglycerate, riboflavin, dihydroxyacetone, shikimate, and many others.
Riboflavin kinaseEdit
Main article: Riboflavin kinase
Riboflavin kinase catalyzes the phosphorylation of riboflavin to create flavin mononucleotide(FMN). It has an ordered binding mechanism where riboflavin must bind to the kinase before it binds to the ATP molecule.[30] Divalent cations help coordinate the nucleotide.[30] The general mechanism is shown in the figure below.
Mechanism of riboflavin kinase.
Riboflavin kinase plays an important role in cells, as FMN is an important cofactor. FMN also is a precursor to flavin adenine dinucleotide(FAD), a redox cofactor used by many enzymes, including many in metabolism. In fact, there are some enzymes that are capable of carrying out both the phosphorylation of riboflavin to FMN, as well as the FMN to FAD reaction.[31] Riboflavin kinase may help prevent stroke, and could possibly be used as a treatment in the future.[32] It is also implicated in infection, when studied in mice.[33]
Thymidine kinaseEdit
Main article: Thymidine kinase
Thymidine kinase is one of the many nucleoside kinases that are responsible for nucleoside phosphorylation. It phosphorylates thymidine to create thymidine monophosphate (dTMP). This kinase uses an ATP molecule to supply the phosphate to thymidine, as shown below. This transfer of a phosphate from one nucleotide to another by thymidine kinase, as well as other nucleoside and nucleotide kinases, functions to help control the level of each of the different nucleotides.
Overall reaction catalysed by thymidine kinase.
After creation of the dTMP molecule, another kinase, thymidylate kinase, can act upon dTMP to create the diphosphate form, dTDP. Nucleoside diphosphate kinase catalyzes production of thymidine triphosphate, dTTP, which is used in DNA synthesis. Because of this, thymidine kinase activity is closely correlated with the cell cycle and used as a tumor marker in clinical chemistry.[34] Therefore, it can sometime be used to predict patient prognosis.[35] Patients with mutations in the thymidine kinase gene may have a certain type of mitochondrial DNA depletion syndrome, a disease that leads to death in early childhood.[36]
Wikimedia Commons has media related to Kinases.
Activation loop
Autophosphorylation
Ca2+/calmodulin-dependent protein kinase
Cyclin-dependent kinase
G protein-coupled receptor
Nucleoside-diphosphate kinase
Phosphatase
Phosphatidylinositol phosphate kinases
Phosphotransferase
Thymidine kinase in clinical chemistry
Thymidylate kinase
Wall-Associated Kinase
^ Siebold, C; Arnold, I; Garcia-Alles, LF; Baumann, U; Erni, B (Nov 28, 2003). "Crystal structure of the Citrobacter freundii dihydroxyacetone kinase reveals an eight-stranded alpha-helical barrel ATP-binding domain". The Journal of Biological Chemistry. 278 (48): 48236–44. doi:10.1074/jbc.M305942200. PMID 12966101.
^ a b Manning G, Whyte DB, et al. (2002). "The protein kinase complement of the human genome". Science. 298 (5600): 1912–1934. doi:10.1126/science.1075762. PMID 12471243.
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