text:
Digital: A Love Story
Available Platforms: FreeLinuxMacPC
Free to play – Early computer interface
Decisions have no impact on story
Released in 2010 Digital: A Love Story lets you step right into developing a n online relationship with a girl as you also attempt to uncover information relating to the downfall of several AIs. While more linear than similar titles the impressive writing, plot and setting ensure this indie visual novel is among the must play for fans of the genre.
With your first computer ever in hand players step into the world of online bulletin boards where you quickly become entangled with a girl named Emilia on the local board. After falling in love with each other though the board goes down with a cryptic message that suggests Emilia needs help.
Set back in time during the era of 1988 the players computer system will similarly drop back in time to the period with a simple interface that resembles an early online bulletin board system. From this board players are able to received messages and communicate with the various game characters, complete with things like item attachments that can be downloaded to your computer to enhance its functionalities. In order to access more boards players must find out their number and manually enter it while also occasionally obtaining illegal long-distance calling cards in order to reach those hosted internationally.
While many of these messages require the player to reply these have minimal impact on the game which opts for a linear storyline rather than a branching one with multiple endings. These replies are never shown to the player and simply inferred by the options you make and the reactions by the characters. Despite being linear the game won't automatically advance and generally requires players to make specific actions before moving onto the next game stage. This process from start to finish will take approximately just over an hour.
Overall trading the usual branching story lines of visual novel games to have a more engaging story is a trade worth accepting for the experience of Digital: A Love Story.
Step back in time to the early internet days.
Join an interesting cyber themed plot.
Visit discussion boards online and interact with several characters.
Solve the mystery of recent AI disappearances.
Free to play title.
Review Platform: PC
This review was first published on December 18, 2016 . Read our update policy to learn more.
Games Like Emily Is Away, Games Like Mystic Messenger


text:
Going gray
With 497 offices worldwide, Ogilvy and Mather builds brands for clients on a global and local scale. Navigating such an enormous market requires flexibility. Providing that flexibility for the last eight years is Jeffrey Bonacci, Senior Creative Systems Engineer and Applications Specialist of North American IT.
To describe his role, Jeffrey serves as the "creative liaison to IT." To describe his work, he says, "I develop ideas on how to implement the technology that will move our business forward."
But that work, according to Jeffrey, has brought gray hairs, which creep up his sideburns.
"The creative professionals have living, breathing workstations, utilizing many emerging technologies that sometimes my team isn't familiar with," said Jeffrey. "I need to maintain inventory, compliance, and enterprise level security and at the same time don't want to dictate how they work on their machines."
Providing his professionals with desktop flexibility generates more gray hair because he has to dedicate more time to inventory tracking and compliance.
Discovering the fountain of youth
With Jamf Pro, Jeffrey was promised a way to turn three weeks of work into a day or even milliseconds. But Jeffrey is not an easy sell.
"I'm not going to deploy a solution if it is not going to work," he said. "I don't have time to coddle. Advertising is a volatile business: We need work done quickly and precisely."
Jeffrey was familiar with Jamf Pro, and he was eager to learn about how it could serve the business. So Jeffrey and the Jamf professionals devised a simple test as part of deployment.
"This test was the deciding factor as to whether we would make the investment," he said.
The business needed to replace a bundled application on 750 Macs. In the past, such a deployment would require Jeffrey to hire 10-15 people to visit every workstation over two days. With Jamf Pro, he created a package in 25 minutes and sent it to a dozen machines in 20 minutes.
"It worked phenomenally," he said. "Of the 750 Macs, I only had four machines that needed additional support."
The triumph of a conquistador
Like an elixir, Jamf Pro has transformed Jeffrey's work day.
"Jamf Pro obliterated the need to do a physical inventory," he said. In seconds, Jeffrey can capture granular detail on all data from the entire network.
"I can drill down into specific operating systems, RAM, drives, peripherals... everything." Jeffrey said. "I also know a machine's entire history—purchase date, serial number, users, and ailments."
Knowing this history and inventory, Jeffrey has been able to maintain compliance and standardize desktops. Jamf Pro handles compliance logistics, so Jeffrey meets SOX requirements, and he didn't sacrifice flexibility for standardization.
"With Jamf Pro, I can get everyone in the same place with the same image without feeling intrusive," said Jeffrey. Most important is remote deployment. "Image creation is so much easier and more efficient. What took days, is now done overnight. I can deploy packages with a click."
Like a conquistador, Jeffrey now commands and explores. He will always have to monitor the network, but now he can design as well.
"I get to decide on how to do my work and then let Jamf Pro execute those decisions," Jeffrey said. "It frees up my time and makes my job less stressful."
He uses that time to facilitate more collaboration and focus on continuing to move the business forward both nationally and internationally. Despite those local and global goals, the stress reduction has kept his gray hair from spreading.
I get to decide on how to do my work and then let Jamf Pro execute those decisions. It frees up my time and makes my job less stressful.
— Jeffrey Bonacci

redpajama_set_name: RedPajamaCommonCrawl


text:
#include <Core/ApplicationPool/Pool.h>

/*************************************************************************
 *
 * Process data structure utility functions for ApplicationPool2::Pool
 *
 *************************************************************************/

namespace Passenger {
namespace ApplicationPool2 {

using namespace std;
using namespace boost;

/****************************
 *
 * Private methods
 *
 ****************************/

ProcessPtr
Pool::findOldestIdleProcess(const Group *exclude) const {
	ProcessPtr oldestIdleProcess;

	GroupMap::ConstIterator g_it(groups);
	while (*g_it != NULL) {
		const GroupPtr &group = g_it.getValue();
		if (group.get() == exclude) {
			g_it.next();
			continue;
		}
		const ProcessList &processes = group->enabledProcesses;
		ProcessList::const_iterator p_it, p_end = processes.end();
		for (p_it = processes.begin(); p_it != p_end; p_it++) {
			const ProcessPtr process = *p_it;
			if (process->busyness() == 0
			     && (oldestIdleProcess == NULL
			         || process->lastUsed < oldestIdleProcess->lastUsed)
			) {
				oldestIdleProcess = process;
			}
		}
		g_it.next();
	}

	return oldestIdleProcess;
}

ProcessPtr
Pool::findBestProcessToTrash() const {
	ProcessPtr oldestProcess;

	GroupMap::ConstIterator g_it(groups);
	while (*g_it != NULL) {
		const GroupPtr &group = g_it.getValue();
		const ProcessList &processes = group->enabledProcesses;
		ProcessList::const_iterator p_it, p_end = processes.end();
		for (p_it = processes.begin(); p_it != p_end; p_it++) {
			const ProcessPtr process = *p_it;
			if (oldestProcess == NULL
			 || process->lastUsed < oldestProcess->lastUsed) {
				oldestProcess = process;
			}
		}
		g_it.next();
	}

	return oldestProcess;
}

/**
 * Calls Group::detach() so be sure to fix up the invariants afterwards.
 * See the comments for Group::detach() and the code for detachProcessUnlocked().
 */
ProcessPtr
Pool::forceFreeCapacity(const Group *exclude,
	boost::container::vector<Callback> &postLockActions)
{
	ProcessPtr process = findOldestIdleProcess(exclude);
	if (process != NULL) {
		P_DEBUG("Forcefully detaching process " << process->inspect() <<
			" in order to free capacity in the pool");

		Group *group = process->getGroup();
		assert(group != NULL);
		assert(group->getWaitlist.empty());

		group->detach(process, postLockActions);
	}
	return process;
}

bool
Pool::detachProcessUnlocked(const ProcessPtr &process,
	boost::container::vector<Callback> &postLockActions)
{
	if (OXT_LIKELY(process->isAlive())) {
		verifyInvariants();

		Group *group = process->getGroup();
		group->detach(process, postLockActions);
		// 'process' may now be a stale pointer so don't use it anymore.
		assignSessionsToGetWaiters(postLockActions);
		possiblySpawnMoreProcessesForExistingGroups();

		group->verifyInvariants();
		verifyInvariants();
		verifyExpensiveInvariants();

		return true;
	} else {
		return false;
	}
}

void
Pool::syncDisableProcessCallback(const ProcessPtr &process, DisableResult result,
	boost::shared_ptr<DisableWaitTicket> ticket)
{
	LockGuard l(ticket->syncher);
	ticket->done = true;
	ticket->result = result;
	ticket->cond.notify_one();
}

void
Pool::possiblySpawnMoreProcessesForExistingGroups() {
	/* Looks for Groups that are waiting for capacity to become available,
	 * and spawn processes in those groups.
	 */
	GroupMap::ConstIterator g_it(groups);
	while (*g_it != NULL) {
		const GroupPtr &group = g_it.getValue();
		if (group->isWaitingForCapacity()) {
			P_DEBUG("Group " << group->getName() << " is waiting for capacity");
			group->spawn();
			if (atFullCapacityUnlocked()) {
				return;
			}
		}
		g_it.next();
	}
	/* Now look for Groups that haven't maximized their allowed capacity
	 * yet, and spawn processes in those groups.
	 */
	g_it = GroupMap::ConstIterator(groups);
	while (*g_it != NULL) {
		const GroupPtr &group = g_it.getValue();
		if (group->shouldSpawn()) {
			P_DEBUG("Group " << group->getName() << " requests more processes to be spawned");
			group->spawn();
			if (atFullCapacityUnlocked()) {
				return;
			}
		}
		g_it.next();
	}
}

/****************************
 *
 * Public methods
 *
 ****************************/

vector<ProcessPtr>
Pool::getProcesses(bool lock) const {
	DynamicScopedLock l(syncher, lock);
	vector<ProcessPtr> result;
	GroupMap::ConstIterator g_it(groups);
	while (*g_it != NULL) {
		const GroupPtr &group = g_it.getValue();
		ProcessList::const_iterator p_it;

		for (p_it = group->enabledProcesses.begin(); p_it != group->enabledProcesses.end(); p_it++) {
			result.push_back(*p_it);
		}
		for (p_it = group->disablingProcesses.begin(); p_it != group->disablingProcesses.end(); p_it++) {
			result.push_back(*p_it);
		}
		for (p_it = group->disabledProcesses.begin(); p_it != group->disabledProcesses.end(); p_it++) {
			result.push_back(*p_it);
		}

		g_it.next();
	}
	return result;
}

ProcessPtr
Pool::findProcessByGupid(const StaticString &gupid, bool lock) const {
	vector<ProcessPtr> processes = getProcesses(lock);
	vector<ProcessPtr>::const_iterator it, end = processes.end();
	for (it = processes.begin(); it != end; it++) {
		const ProcessPtr &process = *it;
		if (process->getGupid() == gupid) {
			return process;
		}
	}
	return ProcessPtr();
}

ProcessPtr
Pool::findProcessByPid(pid_t pid, bool lock) const {
	vector<ProcessPtr> processes = getProcesses(lock);
	vector<ProcessPtr>::const_iterator it, end = processes.end();
	for (it = processes.begin(); it != end; it++) {
		const ProcessPtr &process = *it;
		if (process->getPid() == pid) {
			return process;
		}
	}
	return ProcessPtr();
}

bool
Pool::detachProcess(const ProcessPtr &process) {
	ScopedLock l(syncher);
	boost::container::vector<Callback> actions;
	bool result = detachProcessUnlocked(process, actions);
	fullVerifyInvariants();
	l.unlock();
	runAllActions(actions);
	return result;
}

bool
Pool::detachProcess(pid_t pid, const AuthenticationOptions &options) {
	ScopedLock l(syncher);
	ProcessPtr process = findProcessByPid(pid, false);
	if (process != NULL) {
		const Group *group = process->getGroup();
		if (group->authorizeByUid(options.uid)
		 || group->authorizeByApiKey(options.apiKey))
		{
			boost::container::vector<Callback> actions;
			bool result = detachProcessUnlocked(process, actions);
			fullVerifyInvariants();
			l.unlock();
			runAllActions(actions);
			return result;
		} else {
			throw SecurityException("Operation unauthorized");
		}
	} else {
		return false;
	}
}

bool
Pool::detachProcess(const string &gupid, const AuthenticationOptions &options) {
	ScopedLock l(syncher);
	ProcessPtr process = findProcessByGupid(gupid, false);
	if (process != NULL) {
		const Group *group = process->getGroup();
		if (group->authorizeByUid(options.uid)
		 || group->authorizeByApiKey(options.apiKey))
		{
			boost::container::vector<Callback> actions;
			bool result = detachProcessUnlocked(process, actions);
			fullVerifyInvariants();
			l.unlock();
			runAllActions(actions);
			return result;
		} else {
			throw SecurityException("Operation unauthorized");
		}
	} else {
		return false;
	}
}

DisableResult
Pool::disableProcess(const StaticString &gupid) {
	ScopedLock l(syncher);
	ProcessPtr process = findProcessByGupid(gupid, false);
	if (process != NULL) {
		Group *group = process->getGroup();
		// Must be a boost::shared_ptr to be interruption-safe.
		boost::shared_ptr<DisableWaitTicket> ticket = boost::make_shared<DisableWaitTicket>();
		DisableResult result = group->disable(process,
			boost::bind(syncDisableProcessCallback, _1, _2, ticket));
		group->verifyInvariants();
		group->verifyExpensiveInvariants();
		if (result == DR_DEFERRED) {
			l.unlock();
			ScopedLock l2(ticket->syncher);
			while (!ticket->done) {
				ticket->cond.wait(l2);
			}
			return ticket->result;
		} else {
			return result;
		}
	} else {
		return DR_NOOP;
	}
}

} // namespace ApplicationPool2
} // namespace Passenger

redpajama_set_name: RedPajamaGithub


What are the Best Boiler Systems Available in Woodstock?
My Fireplace in London, Ontario. A hot offer.
If you are looking into getting a high efficiency furnace, here is what to consider How our experts assess your furnace How does ductless heating work? A natural gas fireplace is a great investment, with many benefits.


text:
Novoperzijsko Sasanidsko Carstvo (224./226. – 651.) stoljećima je bilo suparnik Rimskog, kasnije Bizantskog Carstva na Bliskom Istoku, sve do propasti u 7. stoljeću kada su ga osvojili Arapi. Perzija je u doba Sasanida doživjela kulturni procvat koji se nastavio i u doba Abasidskog kalifata.

Ovaj Popis perzijskih vladara iz dinastije Sasanida sastavljen je na temelju novijih istraživanja. Važno je napomenuti da dijelom zbog nedostatka izvora kronologiju sasanidskih vladara nije moguće posve točno odrediti. To se osobito odnosi za razdoblje kraja Sasanidskog Perzijskog Carstva kada je moguće samo okvirno odrediti kronologiju (na primjer u slučaju Hormizda V. i Hozroja IV. koji se ponekad piše i kao Hozroje V.)

 Ardašir I. (224. – 240.)
 Šapur I. (također Sapor, Sabuhr itd.) (240. – 270./272.)
 Hormizd I. (270./272. – 273.)
 Bahram I. (također Varam) (273. – 276.)
 Bahram II. (276. – 293.)
 Bahram III. (293.)
 Narseh (293. – 302.)
 Hormizd II. (302. – 309.)
 Šapur II. (309. – 379.)
 Ardašir II. (379. – 383.)
 Šapur III. (383. – 388.)
 Bahram IV. (388. – 399.)
 Jezdegerd I. (također Jazdgird) (399. – 421.)
 Bahram V. Gor (421. – 439.)
 Jezdegerd II. (439. – 457.)
 Hormizd III. (457. – 459.)
 Peroz I. (459. – 484.)
 Balaš (484. – 488.)
 Kavad I. (488. – 496. i 499. – 531.)
 Zamasp (496. – 499.)
 Hozroje I. Anuširvan (531. – 579.)
 Hormizd IV. (579. – 590.)
 Bahram Čobin (590. – 591.)
 Hozroje II. Parviz (590. – 628.)
 Kavad II. (628.)
 Ardašir III. (628. – 630.)
 Šahrabaraz (630.)
 Boran Perzijska (630. – 631.)
 Azarmedukt (630./632.)
 Hozroje III. (630.); samo u dijelu države
 Hormizd V. (631. – 632.)
 Hozroje IV. (631. – 633.)
 Jezdegerd III. (632. – 651.)

Napomena: Bahram Čobin i Šahrabaraz nisu potjecali iz dinastije Sasanida.

Literatura

 Klaus Schippmann: Grundzüge der Geschichte des sasanidischen Reiches. Wissenschaftliche Buchgesellschaft, Darmstadt 1990.
 Josef Wiesehöfer: Das antike Persien. Aktualisierte Auflage. Albatros, Düsseldorf 2005.

Vanjske poveznice

 Obiteljsko stablo Sasanida (engleski, PDF, 144 KB)

Bilješke

Sasanidski vladari
Sasanidi, vladari
Sasanidi, vladari

redpajama_set_name: RedPajamaWikipedia


text:
Q: Not allowing Android app to be installed on WiFi-only devices I have an application that require the GSM/CDMA radio to be present and the ability to read the devices' IMEI (which is not present on WiFi-only devices).
How would I use the <uses-feature> to restrict my app from being visible to WiFi only devices on Play?
Right now I have this in my manifest:
<uses-feature
    android:name="android.hardware.telephony.gsm"
    android:required="true" />

Should I also add android.hardware.telephony.cdma to allow the app to be installed on devices using GSM and CDMA as well?

A: Use android.hardware.telephony instead.  Otherwise you require a specific type of telephony, which may not be available.  And if you required both CDMA and GSM you'd end up only working on a very small set of phones that have both.
Please note that CDMA doesn't have an IMEI, it has its own identifiers.

redpajama_set_name: RedPajamaStackExchange


You know, I was planning on selling this pack-in game that came with my 360. I was never interested in it before and I didn't see myself playing it much, me not being that big on racing games. To be honest, nothing much has changed really am I'm still not, least of all because of this.
But I will keep the game. Why? Because its a good example of what Xbox Live is all about. Almost everyone I know has it (a requirement for online multiplayer), and setting up races is easy enough so it's fun for that reason alone. There are problems, the most major being that you cannot let a guest play alongside you on Live via split screen - this is disappointing in an age where the PGRs and Halos take this for granted.
The game itself is okay too - it steers (hah) toward simulation rather than arcade style racing but not enough to make it hell boring (I'm looking at you Gran Turismo!). You don't have to spend days tuning up your car in order to get an edge for instance.
But I won't be playing Forza other than online. After all, it is just another racing game. But when I do play it (online) it is pretty darned ace. Vrooom.


Load shedding is back, and nobody's happy about it. But unless you have the money for generators, solar installations, or other expensive alternatives, the reality is that you are at risk of losing power for periods of time until the national grid is stable again.
In our tech-driven world, it's really disruptive to have a few hours without electricity. But losing power doesn't necessarily mean losing productivity. In this article, we look at some key strategies for minimising the blow of load shedding, while also making the most of the electrical downtime.
The current load shedding is subject to fairly reliable schedules - so you can plan ahead. Whether you're supplied by the City of Cape Town or Eskom, keep your schedule close at hand - whether printed or on your mobile device.
You may only log a call for UCT-owned equipment - not for your personal devices.


Fall has come! Everyone is going shopping for trendy fall clothing. And you obviously don't want to be an out-of-fashion woman, do you? So why not update your wardrobe with the latest fashion trends this fall?
Scarves are always an essential item of clothing for women in fall. They not only help you mix clothes effectively, but also help you protect your neck against the cooler fall weather. However, it's not always easy to choose a suitable scarf for this fall, as there are a various types of scarves. For example, in terms of material, scarves have varied from silk and polyester to acrylic and wool, among many others. Therefore, some good advice is to buy scarves according to weather. For instance, in cool weather, silk and polyester scarves are proper choices, while wool ones, which are popularly offered at Urban Outfitters, are suitable for cold weather.
2. Sweaters Sweaters are always one of the must-have fall items in any woman's closet. With their various fashionable designs, women are always "in love with sweaters" in fall. And among the many types of sweaters, cardigans and pullovers with geometric and animal patterns have won the hearts of many women this fall. Besides, you can choose sweaters according to your style. If you love simple clothing, select solid and sweet sweaters from store such as 6pm or Old Navy; otherwise, you can choose the premium and luxurious sweaters of Gap or Express!
3. Coats and Jackets A good coat or jacket will set you in good stead this fall and winter. Not only does it provide you with a fashionable look, but it also keeps your body warm, especially during extreme cold spells. This fall we have welcomed trendy leather trench coats and jackets in black, white, oxblood, red, and denim. Thus, a leather trench coat in the military style should be on your list of fall must-have clothing!
4. Dresses One of the most popular clothing items for any woman is a dress as it shows her feminine side. Lace dresses have continued holding the top position of favorite apparel for women this fall. Leather, metallic and thick cotton dresses with cut-outs in black, white, oxblood, and red are also in vogue. Metallic dresses will always help you shine at parties and events, and remember to wear metallic shoes, clutches and accessories for the perfect ensemble! On the other hand, leather dresses provide you a retro look, and you should wear them with boots for a perfect image! You can find a range of elegant leather, lace, or thick cotton dresses at Urban Outfitters, or you can buy luxurious metallic dresses at Express.
5. Pants Fashion trends may change, but pants never lose their exclusive position in the fashion industry. Thanks to their easy-match feature, pants are always on women's must-have lists for fall clothes. There are many colors of pants for you to choose from in this fall. Besides original black pants, you can diversify your wardrobe with pastel, color block, and especially "huge" color pants such as oxblood, red, green, and cobalt. And you can find such pants at Gap and Old Navy. If you are worried about the price of clothes at these stores, consider using Gap Promo Code and Old Navy Promo Code to save on your purchases!
6. BootsFashionable clothing will not be complete without attractive footwear. When it comes to footwear, boots will be the most wanted item this fall. This year, the military style is becoming the hottest trend in boots. Otherwise, you can choose flat leather boots or retro high-heeled ankle boots for fashionable outfits. You also can consider leather boots with metal details from 6pm.
You have had in your hand must-have clothing items for this fall. Why not go shopping now?


Blocks of duplicated genomic DNA sequence longer than 1000 base pairs are known as low copy repeats (LCRs). Identified by their sequence similarity, LCRs are abundant in the human genome, and are interesting because they may represent recent adaptive events, or potential future adaptive opportunities within the human lineage. Sequence analysis tools are needed, however, to decide whether these interpretations are likely, whether a particular set of LCRs represents nearly neutral drift creating junk DNA, or whether the appearance of LCRs reflects assembly error. Here we investigate an LCR family containing the sulfotransferase (SULT) 1A genes involved in drug metabolism, cancer, hormone regulation, and neurotransmitter biology as a first step for defining the problems that those tools must manage.
Sequence analysis here identified a fourth sulfotransferase gene, which may be transcriptionally active, located on human chromosome 16. Four regions of genomic sequence containing the four human SULT1A paralogs defined a new LCR family. The stem hominoid SULT1A progenitor locus was identified by comparative genomics involving complete human and rodent genomes, and a draft chimpanzee genome. SULT1A expansion in hominoid genomes was followed by positive selection acting on specific protein sites. This episode of adaptive evolution appears to be responsible for the dopamine sulfonation function of some SULT enzymes. Each of the conclusions that this bioinformatic analysis generated using data that has uncertain reliability (such as that from the chimpanzee genome sequencing project) has been confirmed experimentally or by a "finished" chromosome 16 assembly, both of which were published after the submission of this manuscript.
SULT1A genes expanded from one to four copies in hominoids during intra-chromosomal LCR duplications, including (apparently) one after the divergence of chimpanzees and humans. Thus, LCRs may provide a means for amplifying genes (and other genetic elements) that are adaptively useful. Being located on and among LCRs, however, could make the human SULT1A genes susceptible to further duplications or deletions resulting in 'genomic diseases' for some individuals. Pharmacogenomic studies of SULT1Asingle nucleotide polymorphisms, therefore, should also consider examining SULT1A copy number variability when searching for genotype-phenotype associations. The latest duplication is, however, only a substantiated hypothesis; an alternative explanation, disfavored by the majority of evidence, is that the duplication is an artifact of incorrect genome assembly.
Experimental and computational results estimate that 5–10% of the human genome has recently duplicated [1–4]. These estimates represent the total proportion of low-copy repeats (LCRs), which are defined as homologous blocks of sequence from two distinct genomic locations (non-allelic) >1000 base pairs in length. LCRs, which are also referred to in the literature as recent segmental duplications, may contain all of the various sequence elements, such as genes, pseudogenes, and high-copy repeats. A set of homologous LCRs make up an LCR family. Non-allelic homologous recombination between members of an LCR family can cause chromosomal rearrangements with health-related consequences [5–7]. While data are not yet available to understand the mechanistic basis of LCR duplication, mechanisms will emerge through the study of individual cases .
At the same time, the appearance of LCR duplicates may be an artifact arising from one of a number of problems in the assembly of a genome of interest. Especially when classical repetitive sequences are involved, it is conceivable that mistaken assembly of sequencing contigs might create in a draft sequence of a genome a repeat where none exists. In the post-genomic world, rules have not yet become accepted in the community to decide when the burden of proof favors one interpretation (a true repeat) over another (an artifact of assembly). Again, these rules will emerge over time through the study of individual cases.
Through the assembly of many case studies, more general features of duplication and evolutionary processes that retain duplicates should emerge. Although each LCR family originates from one progenitor locus, no universal features explain why the particular current progenitor loci have been duplicated instead of other genomic regions. From an evolutionary perspective, duplicated material is central to creating new function, and to speciation. One intriguing hypothesis is that genes whose duplication and recruitment have been useful to meet current Darwinian challenges find themselves in regions of the chromosome that favor the generation of LCRs.
Browsing a naturally organized database of biological sequences, we identified human cytosolic sulfotransferase (SULT) 1A as a recently expanded gene family with biomedically related functions. SULT1A enzymes conjugate sulfuryl groups to hydroxyl or amino groups on exogenous substrates (sulfonation), which typically facilitates elimination of the xenobiotic by the excretory system . Sulfonation, however, also bioactivates certain pro-mutagenic and pro-carcinogenic molecules encountered in the diet and air, making it of interest to cancer epidemiologists [10, 11]. These enzymes also function physiologically by sulfonating a range of endogenous molecules, such as steroid and thyroid hormones, neurotransmitters, bile salts, and cholesterol .
Three human SULT1A genes have been reported [12, 13]. The human SULT1A1 and 1A2 enzymes are ~98% identical and recognize many different phenolic compounds such as p-nitrophenol and α-naphthol [14–19]. The human SULT1A3 enzyme is ~93% identical to SULT1A1 and 1A2, but preferentially recognizes dopamine and other catecholamines over other phenolic compounds [19–23]. High resolution crystal structures of SULT1A1 and 1A3 enzymes have been solved [24–26]. Amino acid differences that contribute to the phenolic and dopamine substrate preferences of the SULT1A1 and 1A3 enzymes, respectively, have been localized to the active site [27–30].
Polymorphic alleles of SULT1A1, 1A2, and 1A3 exist in the human population [31–33]. An allele known as SULT1A1*2 contains a non-synonymous polymorphism, displays only ~15% of wild type sulfonation activity in platelets, and is found in ~30% of individuals in some populations . Numerous studies comparing SULT1A1 genotypes in cancer versus control cohorts demonstrate that the low-activity SULT1A1*2 allele is a cancer risk factor [34–36], although other studies have failed to find an association . Ironically, the protection from carcinogens conferred by the high activity SULT1A1*1 allele is counterbalanced by risks associated with its activation of pro-carcinogens. For example, SULT1A enzymes bioactivate the pro-carcinogen 2-amino-α-carboline found in cooked food, cigarette smoke and diesel exhaust . The sulfate conjugates of aromatic parent compounds convert to reactive electrophiles by losing electron-withdrawing sulfate groups. The resulting electrophilic cations form mutagenic DNA adducts leading to cancer.
Recently, it has become widely understood that placing a complex biomolecular system within an evolutionary model helps generate hypotheses concerning function. This process has been termed "phylogenomics" . Through our bioinformatic and phylogenomic efforts on the sulfotransferase 1A system, we detected a previously unidentified human gene that is very similar to SULT1A3, transcriptionally active, and not found in the chimpanzee. In addition, we report that all four human SULT1A genes are located on LCRs in a region of chromosome 16 replete with other LCRs. A model of SULT1A gene family expansion in the hominoid lineage (humans and great apes) is presented, complete with date estimates of three preserved duplication events and identification of the progenitor locus. Positively selected protein sites were identified that might have been central in adapting the SULT1A3 and 1A4 enzymes to their role in sulfonating catecholamines such as dopamine and other structurally related drugs.
The human SULT1A1 and 1A2 genes are tandemly arranged 10 kilobase pairs (kbp) apart in the pericentromeric region of chromosome 16, while the SULT1A3 gene is located ~1.7 million base pairs (Mbp) away (Figure 1B and 1C). In addition to the three known SULT1A genes, we found a fourth gene, SULT1A4, by searching the human genome with the BLAST-like alignment tool . SULT1A4 was located midway between the SULT1A1/1A2 gene cluster and the SULT1A3 gene (Figure 1B and 1C).
Genomic organization of the SULT1A LCR family. (A) 30 LCRs (red) aligned to the SULT1A3 LCR (blue). Core sequences of SULT1A and LCR16a families are shown between dashed lines. (B) Chromosome 16 positions of 29 SULT1A3-related LCRs. (C) Known genes, bacterial sequencing contigs, and LCRs (outlined in boxes) in three 350 kbp regions of chromosome 16.
The SULT1A4 gene resided on 148 kbp of sequence that was highly identical to 148 kbp of sequence surrounding the SULT1A3 gene (Figure 1A and Table 1). The high sequence identity between the SULT1A3 and 1A4 genomic regions suggested that they were part of a low copy repeat (LCR) family. This suspicion was confirmed by mining the Recent Segmental Duplication Database of human LCR families . In addition to the four-member SULT1A LCR family, the 148 kbp SULT1A3 LCR was related to 27 other LCRs (Figure 1A and Table 1). Many of the SULT1A3-related LCRs are members of the previously identified LCR16a family [41, 42]. The SULT1A3-related LCRs mapping to chromosome 16 collectively amounted to 1.4 Mbp of sequence – or 1.5% of chromosome 16.
*LCR names are as in Figure 1. †Percent identity is relative to the 1A3 LCR.
To determine if other genes in the SULT super family were also recently duplicated during LCR expansions, we searched the Segmental Duplication Database  for human reference genes located on LCRs. No other complete cytosolic SULT genes were located on LCRs, but 25% of the SULT2A1 open reading frame (ORF) was located on an LCR (Table 2).
The steroid sulfatase gene, which encodes an enzyme that removes sulfate groups from the same biomolecules recognized and sulfonated by SULT enzymes, is frequently deleted in patients with scaly skin (X-linked icthyosis) due to nonallelic homologous recombination between LCRs on chromosome X [43, 44]. As demonstrated by the X-linked icthyosis example, SULT1A copy number or activity in the human population could be modified – with health-related consequences – by nonallelic homologous recombination between LCRs on chromosome 16.
The sequence of the SULT1A4 gene region from the human reference genome was so similar to that of the SULT1A3 region (>99% identity) that the differences were near those that might arise from sequencing error or allelic variation. It was conceivable, therefore, that some combination of sequence error, allelic variation, and/or faulty genome construction generated the appearance of a SULT1A4 gene that does not actually exist. We therefore searched for additional evidence that the SULT1A4 gene was material.
We asked whether any evidence was consistent with the hypothesis of an artificial SULT1A4 LCR from erroneous genome assembly, as opposed to the existence of a true duplicate region. Here, the quality of the genomic sequencing is important. The junction regions at the ends of the SULT1A4 LCR were sufficiently covered; at least nine sequencing contigs overlapped either junction boundary (Figure 1C). This amount of evidence has been used in other studies to judge the genomic placement of LCRs .
As another line of evidence, we compared the nucleotide sequences of the SULT1A4 and 1A3 genomic regions (Table 3). Among the 876 coding positions the only difference was at position 105, where SULT1A4 possessed adenine (A) and SULT1A3 possessed guanine (G). Thus, if two genes do exist, they differ by one silent transition at the third position of codon 35. The untranslated regions, however, contained thirteen nucleotide differences while the introns contained seven additional differences (Table 3). These 21 differences between the SULT1A4 and 1A3 genomic regions disfavor the hypothesis that sequencing errors played a role in the correct/incorrect placement of these LCRs.
* 21 alignment positions are shown where the nucleotide/gapping (-) of the SULT1A4 region differed from that of the SULT1A3 region. Exon and intron names of the SULT1A3 gene are according to . All nucleotides are numbered relative to the first nucleotide of the start codon, which has a value of +1. There was no position 'zero'. The last nucleotide of the coding sequence occurs at position +3,188. Approximately 3 kb of upstream (5' UTR) and downstream (3' UTR) nucleotides were included in the comparison.
The SULT1A4 gene was located near the junction of two LCRs (Figure 1C). For this reason, it was not clear whether SULT1A4 had a functional promoter. We took a bioinformatic approach to address this question. Expressed sequences ascribed to SULT1A3 were downloaded from the NCBI UniGene website . Each sequence was aligned to SULT1A3 and SULT1A4 genomic regions. Based on the A/G polymorphism at the third position of codon 35, five expressed sequences were assigned to SULT1A4 and nine to SULT1A3 (Table 4). Other expressed sequences were unclassified because they did not overlap codon 35. If the SULT1A4 does exist, there is ample evidence from expressed sequences to make conclusions about its transcriptional activity.
*Gene classifications made according to the nucleotide at position 105 as described in the text. †Tissue descriptions were taken from GenBank accessions.
The codon 35 A/G polymorphism was reported as allelic variation in SULT1A3 by Thomae et al. . It is conceivable that Thomae et al. sequenced both SULT1A3 and SULT1A4 because of the identical sequences surrounding them. In their study, 89% of CAA (1A4) and 11% of CAG (1A3) codon 35 alleles were detected in one population. Why were the frequencies not more equal, as would be expected if SULT1A4 is always CAA and SULT1A3 is CAG? One hypothesis is that SULT1A3 is indeed CAG/CAA polymorphic as reported, while SULT1A4 is always CAA. Interestingly, in both the chimpanzee and gorilla, codon 35 of SULT1A3 is CAA. This implies that the ancestral SULT1A3 gene (prior to duplication) likely had a CAA codon. An A to G transition might have been fixed in a fraction of SULT1A3 genes after the divergence of humans and great apes. If this scenario is true, some transcripts assigned to SULT1A4 on the basis of codon 35 may actually be from individuals expressing the ancestral CAA version of SULT1A3.
We aligned the coding sequences of all available SULT1A genes and used various nucleotide distance metrics and tree-building algorithms to infer the gene tree without constraints. The unconstrained topology placed platypus as the out group, with the placental mammals ordered (ox,(pig,(dog,(rodents)),(rabbit,(primates)))). This differed from the topology inferred while constraining for the most likely relationships among mammalian orders (platypus,((dog,(ox,pig)), ((rabbit,(rodents)), primates))) . We considered both trees, and found that the conclusions drawn throughout the paper were robust with regard to these different topologies. Therefore, only the tree inferred while constraining for most likely relationships among mammalian orders is discussed (Figure 2).
SULT1A gene tree. TREx upper-limit date estimates of hominoid SULT1A duplications are shown as Ma in red. KA/KS values estimated by PAML are shown above branches. Infinity (8) indicates a non-reliable KA/KS value greater than 100. The 1A3/1A4 branch is dashed. NCBI accession numbers of sequences used: chimpanzee 1A1 [Genbank:BK004887], chimpanzee 1A2 [Genbank:BK004888], chimpanzee 1A3 [Genbank:BK004889], ox [Genbank:U34753], dog [Genbank:AY069922], gorilla 1A1 [Genbank:BK004890], gorilla 1A2 [Genbank:BK004891], gorilla 1A3 [Genbank:BK004892], human 1A1 [Genbank:L19999], human 1A2 [Genbank:U34804], human 1A3 [Genbank:L25275], human 1A4 [Genbank:BK004132], macaque [Genbank:D85514], mouse [Genbank:L02331], pig [Genbank:AY193893], platypus [Genbank:AY044182], rabbit [Genbank:AF360872], rat [Genbank:X52883].
Using the transition redundant exchange (TREx) molecular dating tool , we placed upper-limit date estimates at the SULT1A duplication nodes (Figure 2). The SULT1A gene family appears to have expanded ~32, 25, and 3 million years ago (Ma). Therefore, the SULT1A duplications likely occurred after the divergence of hominoids and old world monkeys, with the most recent duplication occurring even after the divergence of humans and great apes.
Mouse, rat, and dog genomes each contained a single SULT1A gene. The simplest evolutionary model, therefore, predicted that one of the four hominoid SULT1A loci was orthologous to the rodent SULT1A1 gene. Syntenic regions have conserved order of genetic elements along a chromosomal segment and evidence of synteny between homologous regions is useful for establishing relationships of orthology and paralogy. Human SULT1A1 is most like rodent Sult1a1 in sequence and function and before the advent of whole genome sequencing it was assumed that they were syntenic and therefore orthologous . Complete genome sequences have since emerged and alignments between them are available in the visualization tool for alignments (VISTA) database of human-rodent genome alignments [50, 51]. The VISTA database contains mouse-human pairwise alignments and mouse-rat-human multiple alignments. The multiple alignments were found to be more sensitive for predicting true orthologous regions between rodent and human genomes . We searched the VISTA database for evidence of any human-rodent syntenic regions involving the four SULT1A loci. The more sensitive multiple alignments failed to record any human-rodent syntenic regions involving the SULT1A1, SULT1A2, or SULT1A4 loci but detected synteny involving the SULT1A3 loci and both rodent genomes (Figure 3). These results are indicative of a hominoid specific SULT1A family expansion from a progenitor locus corresponding to the genomic region that now contains SULT1A3. The results from the VISTA database were not as clear when the less sensitive alignment method was employed (Figure 3).
Synteny plots demonstrating SULT1A3 is the progenitor locus of the hominoid SULT1A family. Each box shows a VISTA percent identity plot between a section of the human genome and a section of a rodent genome. Different rodent genomes and alignment methods are indicated as follows: 1 = mouse (Oct. 2003 build) multiple alignment method (MLAGAN); 2 = rat (June 2003 build) multiple alignment method (MLAGAN); 3 = mouse (October 2003 build) pairwise alignment method (LAGAN). Human gene locations are shown above and human chromosome 16 coordinates below.
SULT1A3 and 1A4 LCRs were 99.1% identical overall (Table 1). More careful inspection revealed that the SULT1A3 and 1A4 LCRs were 99.8% identical over the first 120 kbp, but only 98.0% identical over the last 28 kbp (data not shown). This 10-fold difference in percent identities (0.2% vs. 2.0%) suggested that the SULT1A4-containing LCR was produced by two independent duplications. The chimpanzee draft genome assembly aligned with the human genome  provides evidence in support of this hypothesis. There is conserved synteny between human and chimp genomes over the last 28 kbp of the 1A4-containing LCR, but no synteny over the first 120 kbp where the SULT1A4 gene is located (data not shown). This finding and the TREx date estimate for the SULT1A3/1A4 duplication event at ~3 Ma indicate that SULT1A4 is a human invention not shared by chimpanzees – our closest living relatives.
It should be noted that the chimpanzee genome assembly is less reliable than the assembly of the human genome. The coverage is significantly lower, and the methods used for assembly are viewed by many as being less reliable, in part because they relied on the human assembly. Other possibilities, less supported the available evidence, should be considered, including deletion of the chimpanzee SULT1A4 gene since the human-chimp divergence, or failure of the draft chimpanzee genome assembly to detect the 120 kbp segment on which the SULT1A4 gene resides.
From an analysis of gene sequence change over time, molecular evolutionary theory can generate hypotheses about whether duplication has led to functional redundancy, or whether the duplicates have adopted separate functional roles. If the latter, molecular evolutionary theory can suggest how different the functional roles might be by seeking evidence for positive (adaptive) selection for mutant forms of the native proteins better able to contribute to fitness.
Positive selection of protein function can best be hypothesized when the ratio of non-synonymous (replacement) to synonymous (silent) changes normalized to the number of non-synonymous and synonymous sites throughout the entire gene sequence (KA/KS) is greater than unity. Various models of evolutionary sequence change can be used to calculate these ratios. The simplest assumes a single KA/KS ratio over the entire tree (one-ratio). More complex models assume an independent ratio for each lineage (free-ratios), variable ratios for specific classes of sequence sites (site-specific), or variable ratios for specific classes of sequence sites along specified branches (branch-site specific) [53–57].
Estimating the free parameters in each of these models by the maximum likelihood method  enables testing two nested evolutionary models as competing hypotheses, where one model is a special case of another model. The likelihood ratio test (LRT) statistic, which is twice the log likelihood difference between the nested models, is comparable to a χ2 distribution with degrees of freedom equal to the difference in free parameters between the models . Evidence for adaptive evolution typically requires a KA/KS ratio >1 and a statistically significant LRT .
We estimated KA/KS ratios for each branch in the 1A gene tree by maximum likelihood with the PAML program . A typical branch in the SULT1A gene tree had a ratio of 0.16, and the ratio was 0.23 on the branch separating extant SULT1A3/1A4 genes from the single SULT1A gene in the last common ancestor of hominoids (Figure 2). Thus, the KA/KS ratio estimated as an average over all sites did not suggest adaptive evolution along the 1A3/1A4 branch.
We then implemented three site-specific and two branch-site evolutionary models that allow KA/KS ratios to vary among sites. Four of the five models estimated that a proportion of sites (2–8%) had KA/KS >1 (Table 5). Each model was statistically better at the 99 or 95% confidence level than the appropriate null model as determined using the LRT statistic (Table 6). Table 6 lists the specific sites that various analyses identified as being potentially involved in positive selection and a subset of these sites that are changing along the SULT1A3/1A4 branch.
*f.p. is the number of free parameters in each model. †Evidence for positive selection is shown in boldface. Proportions of sites in each KA/KS class, p0, p1, and p2, were not free parameters when in parentheses. Neutral site-specific model assumes two site classes having fixed KA/KS ratios of 0 and 1, with the proportion of sites in each class estimated as free parameters. Selection site-specific model assumes a third proportion of sites with KA/KS estimated from the data. Discrete model assumes 2 or 3 site classes (k) with the proportion of sites, and KA/KS ratios for each proportion, estimated as free parameters. Beta model assumes a beta distribution of sites, where the distribution is shaped by the parameters p and q. Beta+selection model assumes an additional class of sites having a KA/KS ratio estimated from the data. Model A, an extension of the neutral model, assumes a third site class on the 1A3/1A4 branch with KA/KS estimated from the data. Model B, an extension of the discrete model with two site classes (k = 2), also assumes a third site class on the 1A3/1A4 branch with KA/KS estimated from the data.
*In parentheses for each positively selected site is the posterior probability that the site belongs to the class with KA/KS >1. Posterior probabilities >90% are bold-face. Positively selected sites also experiencing non-synonymous change on the 1A3/1A4 branch are underlined.
A hypothesis of adaptive change that is based on the use of KA/KSvalues can be strengthened by joining the molecular evolutionary analysis to an analysis based on structural biology [62, 63]. Here, we ask whether the sites possibly involved in an episode of sequence evolution are, or are not, randomly distributed in the three dimensional structure. To ask this question, we mapped the sites to the SULT1A structure (Figure 4). Sites holding amino acids whose codons had suffered synonymous replacements were evenly distributed throughout the three-dimensional structure of the enzyme, as expected for silent changes that have no impact on the protein structure and therefore cannot be selected for or against at the protein level (Figure 4). In contrast, sites experiencing non-synonymous replacements during the episode following the duplication that created the new hominoid gene are clustered on the side of the protein near the substrate binding site and the channel through which the substrate gains access to the active site (Figure 4 and Table 7). This strengthens the hypothesis that replacements at the sites are indeed adaptive. The approach employed here based on structural biology does not lend itself easily to evaluation using statistical metrics. Rather, the results are valuable based on the visual impression that they give, and the hypotheses that they generate.
Non-synonymous changes along the 1A3/1A4 branch cluster on the SULT1A1 enzyme structure [PDB: 1LS6] . Red sites experienced non-synonymous changes, green sites experienced synonymous changes. The PAPS donor substrate and p-nitrophenol acceptor substrates are shown in blue. Image was generated using Chimera .
* Sites underlined were identified as being positively selected using the branch-site specific models. †Posterior probabilities that the ancestral residues are correct, conditional on the model of sequence evolution used.
We then examined literature where amino acids had been exchanged between SULT1A1 and SULT1A3. One of the sites, at position 146, identified as being involved in adaptive change, is known to control substrate specificity in SULT1A1 and 1A3 [27–30]. The remaining sites identified are nearby.
An interesting question in post-genomic science asks how to create biological hypotheses from various drafts of whole genome sequences. In generating these hypotheses, it is important to remember that a genomic sequence is itself a hypothesis, about the chemical structure of a small number of DNA molecules. In many cases, biologists wish to move from the genomic sequence, as a hypothesis, to create hypotheses about biological function, without first "proving" the genome sequence hypothesis.
This type of process, building hypotheses upon unproven hypotheses, is actually common in science. In fact, very little of what we believe as fact is actually "proven"; formal proof is virtually unknown in science that involves observation, theory, and experiment. Rather, scientists generally accumulate data until a burden of proof is met, with the standards for that burden being determined by experience within a culture. In general, scientists have an idea in an area as to what level of validation is sufficient to avoid making mistakes an unacceptable fraction of the time, and proceed to that level in their ongoing work, until they encounter a situation where they make a mistake (indicating that a higher standard is needed), or encounter enough examples where a lower standard works, and therefore come to accept a lower standard routinely .
Genomics has not yet accumulated enough examples for the culture to define the standards for a burden of proof. In the example discussed here, several lines of reasoning would be applied to analyze the sulfotransferase gene family. First, the fact that the draft genome for chimpanzee contains three paralogs, while the draft genome for human contains four, would normally be interpreted (as it is here) as evidence that an additional duplication occurred in the time since chimpanzee and humans diverged. It would also, however, be consistent with the loss of one of four hypothetical genes present in the common ancestor of chimpanzee and humans in the lineage leading to chimpanzee. Another possibility is that the finishing stages of the chimpanzee genome project will uncover a SULT1A4 gene.
Normally, one would resolve this question using an out group taxon, a species that diverged from the lineage leading to chimpanzee and human before chimpanzee and human themselves diverged. The nearest taxa that might serve as an out group today are, however, rat and mouse. As noted above, they diverged so long ago (ca. 150 MY separates contemporary rodents from contemporary primates) that the comparison provides no information. And no closer out group taxon (e.g., orangutan) has had its genome completely sequenced.
Here, the two hypotheses (duplication versus loss after the chimpanzee-human speciation) are distinguished (to favor post-speciation duplication) based on an analysis of the silent nucleotide substitutions using the TREx metric. The very small number of nucleotide differences separating the SULT1A3 and SULT1A4 coding regions favors the generation of the two paralogs after chimpanzee and human diverged.
This comparison, however, potentially suffers from the statistics of small numbers. The number of differences in the coding region (exactly one) is small. By considering ~10 kbp of non-coding sequence, however, additional differences were found. It is possible that in the assembly of the human genome, a mistake was made that led to the generation of a SULT1A4 region that does not actually exist. In this hypothesis, the ~20 nucleotide differences between the SULT1A3 and SULT1A4 paralogs must be the consequence of allelic polymorphism in the only gene that exists. This is indeed how some of the data were initially interpreted.
Does the preponderance of evidence favor the hypothesis of a very recent duplication to generate a pair of paralogs (SULT1A3 and SULT1A4)? Or does the evidence favor the hypothesis that the SULT1A4 gene is an illusion arising from gene assembly error coupled to sequencing errors and/or allelic variation at ca. 20 sites? The culture does not yet have a standard of assigning the burden of proof here, although a choice of hypothesis based simply on the count of the number of mistakes that would need to have been made to generate each hypothesis (none for the first, at least three for the second) would favor the former over the latter. Thus, perhaps naively, the burden of proof now favors the former, and we may proceed to generate the biological hypothesis on top of the genomic hypothesis.
Here, the hypothesis has immediate pharmacogenomic and genomic disease implications due to the specific functional behaviors of SULT1A enzymes. LCR-mediated genomic rearrangements could disrupt or amplify human SULT1A gene copy number. Given our current environmental exposure to many forms of carcinogens and pro-carcinogens that are either eliminated or activated by SULT enzymes, respectively, it is plain to see how SULT1A copy number variability in the human population could underlie cancer susceptibilities and drug or food allergies.
The majority of evidence indicates that a new transcriptionally active human gene, which we refer to as SULT1A4, was created when 120 kbp of chromosome 16 duplicated after humans diverged from great apes. Thus, SULT1A4, or possibly another gene in this region, is likely to contribute to distinguishing humans from their closest living relatives. It is also conceivable that an advantage in gene regulation, as opposed to an advantage from gene duplication, was the driving force behind the duplication of this 120 kbp segment. While cause and effect are difficult to separate, the examples presented here support the hypothesis that genes whose duplication and recruitment are useful to meet current Darwinian challenges find themselves located on LCRs.
The SULT1A4 gene is currently the most obvious feature of the duplicated region and has been preserved for ~3 MY without significant divergence of its coding sequence. One suggestion for the usefulness of SULT1A4 is that it expanded sulfonating enzymes to new tissues. The SULT1A4 gene is located only 10 kbp upstream from the junction boundary of its LCR and 700 kbp away from the SULT1A3 locus. It is possible, therefore, that promoter elements from the new genomic context of the SULT1A4 gene would drive its expression in tissues where SULT1A3 is not expressed – a hypothesis testable by more careful transcriptional profiling.
Multiple SULT1A genes were apparently useful inventions by our stem hominoid ancestor. Following the duplication of an ancestral primate SULT1A gene ~32 Ma, positive selection acted on a small proportion of sites in one of the duplicates to create the dopamine sulfonating SULT1A3 enzyme. In the example presented here, the evidence of adaptive change at certain sites is corroborated by the ad hoc observation that the sites cluster near the active site of the protein. The well known substrate binding differences at the active sites of SULT1A1/1A2 and SULT1A3 (and now SULT1A4) substantiate these findings.
When studying well-characterized proteins as we have done here, episodes of functional change can be identified by piecing together several lines of evidence. It is not immediately possible, unfortunately, to assemble as much evidence for the majority of proteins in the biosphere. Thus, an important goal in bioinformatics is to recognize the signal of functional change from a restricted amount of evidence. Of the three lines of evidence employed here (codon-based metrics, structural biology, and experimental), structural biology, with its obvious connections to protein function and impending growth from structural genomics initiatives, will probably be the most serviceable source of information for most protein families. This should be especially true for protein families not amenable to experimental manipulation, or with deep evolutionary branches where codon-based metrics are unhelpful. If we are to exploit the incontrovertible link between structure and function, however, new structural bioinformatic tools and databases relating protein structure to sequence changes occurring on individual branches are much needed.
This bioinformatic study makes several clear predictions. First, a PCR experiment targeted against the variation between the hypothetical SULT1A3 and SULT1A4 human genes should establish the existence of the two separate genes. Second, a reverse transcription-PCR experiment would be expected to uncover transcriptional activity for the SULT1A3 and SULT1A4 human genes. Since this paper was submitted, these experiments have been done, and indeed confirm our predictions made without the experimental information . Further, after this manuscript and its computationally-based predictions were submitted for publication, a largely finished sequence for chromosome 16 has emerged  that confirms our analysis here in every respect.
The July 2003 human reference genome (based on NCBI build 34) was queried with the SULT1A3 coding region using the BLAST-like alignment tool , and search results were visualized in the UCSC genome browser . Two distinct locations on chromosome 16 were identified as equally probable. One location was recognized by NCBI Map Viewer  as the SULT1A3 locus. The other locus was dubbed SULT1A4 following conventional naming for this family. The coding sequence and genomic location of SULT1A4, as well as expressed sequences derived from SULT1A4, have been deposited with the GenBank Third Party Annotation database under accession [Genbank:BK004132].
To determine the extent of homology between the SULT1A3 and 1A4 genomic locations, ~500 kbp of sequence surrounding SULT1A3 and ~500 kbp of sequence surrounding SULT1A4 were downloaded from NCBI and compared using PIPMAKER [69, 70]. Before submitting to PIPMAKER, high-copy repeats in one of the sequences were masked with REPEATMASKER .
The Human Recent Segmental Duplication Page  was consulted to identify other LCRs related to the SULT1A3-containing LCR. Chromosomal coordinates of 30 SULT1A3-related LCRs were arranged in GFF format and submitted to the UCSC genome browser as a custom track. Sequences corresponding to the chromosomal coordinates of the 30 LCRs were then downloaded from the UCSC genome browser and parsed into separate files. Each LCR was aligned with the SULT1A3-containing LCR using MULTIPIPMAKER . The Segmental Duplication Database  was used to examine the duplication status of each gene in the cytosolic SULT super family.
The bacterial artificial chromosome contigs supporting each member of the SULT1A LCR family, and the known genes within each LCR, were inspected with the UCSC genome browser . The DNA sequences of nine bacterial artificial chromosome contigs supporting the SULT1A4 genomic region [NCBI Clone Registry: CTC-446K24, CTC-529P19, CTC-576G12, CTD-2253D5, CTD-2324H19, CTD-2383K24, CTD-2523J12, CTD-3191G16, RP11-28A6] and seven contigs supporting the SULT1A3 region [NCBI Clone Registry: CTD-2548B1, RP11-69O13, RP11-164O24, RP11-455F5, RP11-612G2, RP11-787F23, RP11-828J20] were downloaded from the UCSC genome browser website.
The MASTERCATALOG was used for performing initial inspections of the SULT gene family and for delivering a non-redundant collection of SULT1A genes. Additional SULT1A ORFs were extracted from gorilla working draft contigs [Genbank:AC145177] (SULT1A1 and 1A2) and [Genbank:AC145040] (SULT1A3) and chimpanzee whole genome shotgun sequences [Genbank:AACZ01082721] (SULT1A1), [Genbank:AADA01101065] (SULT1A2), and [Genbank:AACZ01241716] (SULT1A3) using PIPMAKER exon analysis. These new SULT1A genes have been deposited with the GenBank Third Party Annotation database under accession numbers [Genbank:BK004887-BK004892]. DNA sequences were aligned with CLUSTAL W . The multiple sequence alignment used in all phylogenetic analyses is presented as supplementary data [see Additional file 1]. Pairwise distances were estimated under various distance metrics (Jukes-Cantor, Kimura 2-parameter, and Tamura-Nei) that account for among-site rate variation using the gamma distribution . Phylogenies were inferred using both neighbor-joining and minimum evolution tree-building algorithms under the following constraints ((((primates), rodents), (artiodactyls, carnivores)), platypus). Phylogenetic analyses were conducted using the MEGA2 v2.1  and PAUP* v4.0  software packages.
Parameter estimates of site class proportions, KA/KS ratios, base frequencies, codon frequencies, branch lengths, and the transition/transversion bias were determined by the maximum likelihood method with the PAML v3.14 program . Positively selected sites, posterior probabilities, and marginal reconstructions of ancestral sequences were also determined using PAML. Sites experiencing synonymous changes along the 1A3/1A4 branch were recorded by hand from an ancestral sequence alignment.
Starting with aligned DNA sequences, the number (n) of two-fold redundant codons (Lys, Glu, Gln, Cys, Asp, Phe, His, Asn, Tyr) where the amino acid had been conserved in pairs of aligned sequences, and the number of these codons where the third position was identically conserved (c) were counted by the DARWIN bioinformatics platform [80, 81]. The pairwise matrix of n and c values for all SULT1A genes is presented as supplementary data [see Additional file 2]. The c/n quotient equals the fraction of identities (f2) in this system, or the transition redundant exchange (TREx) value . TREx values were converted to TREx distances (kt values) by the following equation: kt = - ln [(f2 - Eq.) / (1 - Eq.)], where k is the rate constant of nucleotide substitution, t is the time separating the two sequences, and Eq. is the equilibrium state of the TREx value . The equilibrium state of the TREx value was estimated as 0.54 for primates, and the rate constant at two-fold redundant sites where the amino acid was conserved (k) was estimated as 3.0 × 10 -9 changes/site/year for placental mammals (T. Li, D. Caraco, E. Gaucher, D. Liberles, M. Thomson, and S.A.B., unpublished data). These estimates were determined by sampling all pairs of mouse:rat and mouse:human orthologs in the public databases and following accepted placental mammal phylogenies and divergence times [82, 83]. Therefore, the date estimates reported are based on the contentious assumptions that (i) rates are constant at the third position of two-fold redundant codons across the genome, (ii) the fossil calibration points are correct, and (iii) the mammalian phylogeny used is correct. Branch lengths were obtained for the constrained tree topology from the pairwise matrix of TREx distances using PAUP* v4.0. Upper-limit date estimates for nodes corresponding to SULT1A duplication events were obtained by summing the longest path of branches leading to a node and dividing that value by k.
Human-chimpanzee genome alignments were inspected at the UCSC Genome Browser. Human-rodent genome alignments were examined with the VISTA Genome Browser [50, 51, 84]. VISTA default parameters were used for drawing curves. Alignments constructed using both the pairwise method (LAGAN) and the multiple alignment method (MLAGAN) between the human genome builds frozen on April 2003 or July 2003 and both rodent genomes were inspected.
All expressed sequences ascribed to SULT1A3 were downloaded from NCBI UniGene  and aligned with SULT1A3 and SULT1A4 genomic regions using PIPMAKER. Alignments were inspected for the polymorphism in codon 35, as well as any other potential patterns, to determine whether they were derived from SULT1A3 or SULT1A4.
We thank the Foundation for Applied Molecular Evolution for providing computational resources. This work was supported by grant DOD 6402-202-L0-G from the USF Center for Biological Defense, and by an NIH post-doctoral fellowship to M.E.B.
M.E.B carried out the study and drafted the manuscript. S.A.B participated in designing the study and preparing the manuscript.


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Nareh (persiska: نره) är en ort i Iran.   Den ligger i provinsen Hormozgan, i den södra delen av landet,  km söder om huvudstaden Teheran. Nareh ligger  meter över havet och antalet invånare är .

Terrängen runt Nareh är varierad. Den högsta punkten i närheten är  meter över havet,  km nordost om Nareh. Runt Nareh är det ganska glesbefolkat, med  invånare per kvadratkilometer. Närmaste större samhälle är Keseh,  km sydost om Nareh. Trakten runt Nareh är ofruktbar med lite eller ingen växtlighet.

I trakten råder ett hett ökenklimat. Årsmedeltemperaturen i trakten är  °C. Den varmaste månaden är juni, då medeltemperaturen är  °C, och den kallaste är januari, med  °C. Genomsnittlig årsnederbörd är  millimeter. Den regnigaste månaden är januari, med i genomsnitt  mm nederbörd, och den torraste är juni, med  mm nederbörd.

Kommentarer

Källor

Orter i Hormozgan


Is social media changing or re-wiring our teens' brains in the Digital Age?
Social media has become an integral part of a teenager's life. Teens aged between 13 to 18 years old spend 9 hours a day online, and 45 percent of teen users agree that social media is an important part of their lives. These "digital natives" are closely identified with technology and they cannot live without it. Today's teens are living a hyper-connected life which may lead to online safety issues such as sexting or cyberbullying. These are just some of the risks teenagers are facing while they are online.
Social networking may have negative effects on our teen's brains, but it is also re-wiring their brains for a digital future. Be it good or bad, here is how social media affects teenagers.
Adolescence is a critical phase in anyone's life. It is when a person's identity is formed and building relationships with peers. Adolescents want to pursue autonomy, stand out from the crowd, and fit in with their peers. Since "fitting in" is important for every teen, social networking sites became the new avenues for developing adolescent relationships. It is easier for them express their points of view while receiving immediate feedback from online peers. Joining online groups also helps teenagers develop their identities.
A simple Facebook "Like", for example, triggers the reward center of a teenager's brain. This area of their brain becomes more active when they receive more "Likes" or positive comments. Also, teens are most likely to "Like" photos if their peers also "Liked" them. Peer influence is amplified by social media and teens show risky behaviors while online. Since their experiential systems are still developing, their capacity for self-regulation is still incomplete. However, social media helps teens develop their brain through online socialization and mental stimulation.
Teens are always connected – from their smartphones to their laptops – which makes them "disconnected" from the real world. This is a cause for concern because teens are missing critical social skills. Vocal reactions, facial expressions, and body language are important in face-to-face communication. Without these, they will have difficulties interacting with others as they reach adulthood.
Aside from missing critical social skills, teens who are always connected learn to live "dual lives". Some become online bullies while others "steal" another person's identity. This could be due to pressure from online friends or their innate desire to take risks. These risky behaviors may lead to run-ins with the law.
The impact of social media on teenagers is not all negative; it also has its own merits. Our brain's plasticity changes when we learn something new. When a teen spends time on social media, it can affect his or her brain. Creating podcasts, writing blogs, or joining online communities are examples of learning something new. Most teenagers also utilize social media to gather information for their school projects and research assignments. It also serves as a platform for online educational collaborations with teachers and classmates.
Since technology changed the world, teenagers need to be technologically adept in keeping up with the times. Social media can help them hone their digital skills for the future.
Social media is the future of networking and communication. We need to prepare our teenagers for a better future. Keep them safe online with MomSecure's premium cyber services.
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55735 Magdeburg è un asteroide della fascia principale. Scoperto nel 1987, presenta un'orbita caratterizzata da un semiasse maggiore pari a 2,6130921 UA e da un'eccentricità di 0,2846698, inclinata di 11,00236° rispetto all'eclittica.

Collegamenti esterni

Corpi celesti scoperti nel 1987
Magdeburg


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Home / Feature Articles / Ghana's poultry farmers battling for survival as country imports $200m frozen chicken
Ghana's poultry farmers battling for survival as country imports $200m frozen chicken
August 22, 2011 Feature Articles 2 Comments
Ghana's poultry farmers are struggling to survive crippling competition from their counterparts in developed countries as the country imports $200 million worth of chicken every year.
The major factors behind the declining state of Ghana's poultry industry are varied and complex, but the most significant is government policy towards the sector's growth.
In small remote communities of Ghana, poultry farming is everything. It is the mainstay of rural communities, providing the major and — in some cases — the only source of income for many inhabitants.
But failure of successive governments to come out with clear policies that will create much protection for the local poultry industry has triggered the import surge of frozen chicken from the United States of America (USA) and the European Union (EU).
Worse still, imported chicken is being sold at below the cost of local chicken, and farmers in Ghana simply cannot compete — resulting in the collapse of dozens of farms and the loss of hundreds of jobs.
Last year alone, the EU, USA and Brazil together exported over 200,000 tonnes of frozen chicken to Ghana, valued at US$200 million.
In 2002, more than 26,000 tonnes of chicken was imported into the country, mostly from the EU where farmers receive generous subsidies for production. In 2005, the figure was estimated to be as high as 50,000 tonnes. Ghana imports almost one-third of the EU's total frozen chicken that goes to Africa.
At a recent debate on the topic "Is Importing Chicken Good for Ghana?" organised by Channel Two Communications, a strategic communications and media company, poultry farmers expressed their dissatisfaction with the status quo, blaming government for letting the poultry industry down.
"I don't think the government sees agric as an important tool – that's how I see it," says Alhaji Abdul-Salam, Managing Director of Akate Farms, one of the largest poultry farms in Ghana.
But Dr. Yao Graham at Accra-based research and advocacy organisation, Third World Network-Africa, attributes the demise of the industry to various factors including government policies.
"I'm not interested in the importers. Importers are entrepreneurs – they will find other opportunities in the economy, if the economy is doing well.
"I'm interested in the policies which create opportunity to import poultry – as having greater weight than the policies which stimulate local production," he says.
Unfair advantage
The Managing Director of Sydel Farms, Kenneth Quartey, explains that Ghana's development partners invest about $240 billion a year in their countries through subsidies in agriculture.
"That's a capital base that is difficult to compete with when you're looking at it from the perspective of developed versus under-developed countries," adds Quartey.
Several Central and West African nations are victims of injustice by the US and EU. These countries subsidise their agricultural producers, ignoring the rules of the World Trade Organisation (WTO).
The U.S. and the EU are the 'subsidy superpowers', accounting for over 60 percent of rich- country agricultural support spending.
Europe spends more in absolute terms—and its subsidies represent a larger share of the value of farm output.
However, the U.S. spends more per farmer. It also concentrates subsidies on a narrower range of commodities.
EU and U.S. subsidies matter to the rest of the world because of their dominant position in global markets. On the surface, the argument against subsidies is quite revealing.
Dr. Graham notes: "They get subsidies for keeping land in production. Things which are in surplus are bought by their governments.
"Once bought, a way has to be found to let them go. In the U.S., for instance, the amount of subsidies given to cotton farmers was more than the export value of all cotton produced in West Africa."
Quartey, who is also a former president of the Ghana Poultry Farmers Association, remarks: "You can't look at just one product in the food-chain, because a subsidy in the downstream of a product's food-chain is effectively a subsidy for everything above.
"For instance, if you have heavy subsidies for maize production, you're effectively subsidising the cost of poultry production – because it has an impact on the cost of feed, which is a major part of the cost of poultry. And hence poultry can lead on the table at a much cheaper price."
But the debate over agricultural subsidies is often clouded by legal language and technical jargon. US officials insist their country is in compliance because its subsidies (those that fall under WTO rules) do not distort international trade.
US officials also accuse developing countries of lumping all US subsidies in a single basket, even though WTO rules lay out different schedules for different types of support. But leaders and activists in developing countries insist the US is not playing fair.
Interest rates in Ghana far exceed the international norm. A farmer in the U.S. borrows at 4 percent, while his Ghanaian counterpart pays anything up to 28 percent. And loans are not easy to come by because banks see agriculture as high-risk.
Commenting on the issue, Charles Otoo, General Manager of First National Bank, says: "Basically – say for poultry – you appreciate the fact that the initial investment by the promoter himself is huge, because of land acquisition, what he has to go through with the preparations, and [the fact that] the equipment they bring in is specialised.
"For huge investments, what kind of collateral do they have to support it? And if you look at the competition, and the fact that the imported ones are much, much cheaper, then you see – even if you support, and they're able to produce – the marketing then becomes a problem. So the risk is very high."
While foreign poultry farmers receive substantial support from their governments, Ghanaian farmers receive none.
Otoo explained that Ghanaian poultry farmers put in everything to buy feed and pay duties at the ports, adding that, "we don't even give them any tax incentives. And it's a huge problem."
In a country endowed with abundant fertile land, poultry farmers have to import maize – a major component in chicken feed – because there isn't sufficient local supply.
And what is available costs the Ghanaian poultry farmer double what it costs his/her American counterpart – because of mechanisation.
While the average Ghanaian farm yields 10 bags of maize per acre, the same land in Brazil, for example, yields 36 bags.
"If we want to compete, I believe we should learn from other places – South Africa, Brazil. They empower their farmers to do maize, soya, rice – we have all this in the country. We can easily do that. What are we doing?" asks Alhaji Abdul-Salam.
IMF, WTO under scrutiny
The International Monetary Fund's role is to oversee the global financial system and improve support to countries needing financial assistance – through loans, debt relief and aid.
But there are strings attached – along with aid comes IMF's right to interfere in the recipient's economic policy.
Given that the IMF is chief proponent of the free market and trade liberalisation, this means that recipient countries must open their markets to international trade, recognise the private sector as the market's driving force and limit state intervention in the economy.
Ghana is heavily dependent on aid, and has agreed to all of these conditions – and hence the low tariffs and lack of subsidies for farmers. Those are the rules, but the farmers aren't buying them.
Quartey counters: "It contradicts the sovereignty of a nation – because a nation is there to provide opportunity for its people first and foremost, and the rest of the world second.
"Hopefully we will do it in such a manner that everyone in the world benefits. But when you have a system where only one part of the world is going to benefit, and the other is going to suffer, I don't think it will sell – no matter how many treaties you get signed. The implementation will fail."
Dr. Graham shares Quartey's pain. He says that despite all the treaties signed, and international commitments to free and fair trade, many first-world countries haven't lived up to the spirit of their pledges.
"Their farmers are still subsidised and their markets protected. And they get away with it. It's a frequently-heard criticism that the World Trade Organisation (WTO) is not impartial, and has a bias towards rich countries and multinational corporations," says Dr. Graham.
The growing consensus is that much of the blame also lies with the shortcomings of the WTO pact that was intended to fairly govern trade in agricultural products, the Agreement on Agriculture.
The agreement, which came into force in 1995, in theory requires all member countries to reduce subsidies that hinder trade.
But numerous loopholes, and rules weighted in favour of the more dominant members of the WTO, have not only allowed industrial countries to avoid reducing agricultural subsidies, but to continue raising them in some cases.
"They will give us money and come and sell their products – and take that money back. And so we remain poor," comments Alhaji Abdul-Salam.
He adds: "We're giving them employment over there, and we're denying our people employment here. They're manufacturing their cars, their planes, cloths, shoes, everything, and selling it to us, and we sit down for them to come and take the agric we've inherited from our great-grandfathers."
"They're telling us – you relax. We'll give you food to eat. And we just say yes, yes – we will relax. And all the time the tears are going in there. We have to one day take a bold decision for us to be able to move forward."
Despite punitive threats from the IMF and World Bank, Nigeria didn't trouble itself with raising tariffs – they simply banned the importation of poultry outright, and today are enjoying a thriving industry, with big plans for regional expansion.
Bans aren't the only option in the regulations of the WTO, the body that policies the lifting of trade barriers. Provision is made to protect developing nations.
If a specific domestic industry is threatened by increased imports, that member country may legally raise its tariff and restrict imports.
Armed with the regulation, the Ghana Poultry Farmers Association petitioned President John Kuffour's Administration in 2003 to raise import tariffs from the current 20 percent.
"Good step, but the tariff was never applied – because they gave in to pressure from the IMF, who claimed it was not in the interest of the poor," says an angry Dr. Graham.
Dr Graham says the IMF has never had the poor as its primary concern. "They put pressure on the government and they never applied the tariff –which was a terrible act – because the decision of a sovereign parliament can be put under pressure by the IMF."
Loud mouth, no action
Government keeps repeating promises to increase taxes on imported chicken, and help farmers to acquire equipment.
Dr. Tia Alfred Sugri, Ghana's Deputy Minister of Agriculture in-charge of Livestock, says government is finding ways to use tariff and non-tariff measures to restrict the importation of chicken into the country.
When asked the timeline for implementing them, Sugri said: "We've started discussions on the measures with stakeholders, and very soon we will implement them. We're capable of serving our people better provided these hurdles are cleared."
But Dr. Graham puts it succinctly: "The elite – their outlook about what this country needs – is too subordinate to other people's vision. Whether the New Patriotic Party (NPP), the National Democratic Congress (NDC) or the Convention People's Party (CPP) – they're all exactly the same.
"The Ghanaian elite love to be praised by the West. They love it when Obama comes and says you're the model to the world. They love it when Tony Blair or some such character, comes around and says you are the model, the fastest, and quickest reforming. You're number five in the world; you're going to become number two, and so on. There's no qualitative evaluation."
By Michael Sarpong Bruce
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OK so what are the Poultry farmers going to do ?? complain about IMF..lets get real IMF or Goverment policies will not change today or in the next 10years, so stop complaining and develop ways of competing….
jnr
@ P . I agree with you 100%.


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JOE PUBLIC completed a triumphant 2005 Sportworld Super League campaign with a 2-0 victory over second-placed Crab Connection in the final round of action on Saturday.
In front of their home supporters at the Marvin Lee Stadium, Tunapuna, the "Eastern Lions" Joe Public broke the deadlock in the 77th minute courtesy a Roen Nelson penalty, while Carlington Smith's 85th minute goal guaranteed the hosts their 19th win of the season. Meanwhile, Couva Players United came from a goal down to defeat Stokely Vale 3-2 at Gilbert Park, Couva yesterday. Devon Leacock put Stokely Vale in front after six minutes of play before Quami Knights levelled the scores in the 27th.
Keith Williams put Couva 2-1 up in the 48th but Kayode Legall equalised in the 74th. Ten minutes later, Aaron Downing found the back of the net to seal with win for Couva. In yesterday's other fixture, PLIPDECO Caroni whipped Maraval Youth Academy 3-1 at the Trinity College Ground, Moka, Maraval. Former national Under-17 captain Roderick Anthony got Caroni's first strike in the 22nd while Jason Cudjoe doubled the lead eight minutes later. Dwayne Charles notched the third item for the visitors, in the 55th minute, while Lawrence Davis' 72nd goal was scant consolation for Maraval, who finished the season 11th in the 12-team table.


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Corey Mitchell,
co-founder, festival director,
& programming director
Housecore Horror Film Festival
Founded by heavy metal icon Phillip H. Anselmo and author Corey Mitchell, the Housecore Horror Film Festival debuted last year with an impressive line-up of old and new genre films, a tribute to Lucio Fulci, and Italian prog rock band Goblin performing its score to Dario Argento's 1977 Suspiria. This year's Housecore Horror Film Festival will feature cast reunions of both The Texas Chainsaw Massacre and The Texas Chainsaw Massacre 2; a tribute to the late Marilyn Burns; the world premiere of American Guinea Pig; screenings of festival and indie faves The Babadook, Circus of the Dead, Dead Snow 2: Red vs. Dead, and Hellion; retrospective screenings of such chillers as Creepers, Race With the Devil, and Shock Waves; and performances by Danzig, GWAR, Napalm Death, and Phillip H. Anselmo's Superjoint. The Housecore Horror Film Festival will run Oct. 23-26 at Emo's and Midway's.
Aired: Oct. 9, 2014
Web site: http://housecorehorrorfilmfestival.com/


Home /Psychic/Can You Force Love with a Psychic Reading?
After a breakup, the pain can be devastating, especially if many years of marriage and children are involved. You may feel desperate to get back together with the one you love, even if it means trying to force his or her return through some kind of spell. But a psychic reading can't force that person to come back. At best, you might just waste money on back-to-back psychic readings that give you the same verdict; at the worse, you might get sucked in by a "psychic reader" who has bad ethics and promises you the moon for a lot of money and then disappears.
The simple fact of the matter is that people have choices and free will. So, even if a psychic reading shows that it is best for the two of you to be together, your love interest might refuse to do so. Or the reading may indicate that you should become a nun, but you may never join the convent. If you feel like you have to force your lover to be with you, you probably don't actually love that person at all. Give yourself some time, and if you're a "forcer," you'll look back in a few years and wonder why you ever wanted that in the first place. A true love will want the other person to be happy, even if the two of you are not together.
Even though many psychic reading practitioners say that they offer "love spells," be dubious. A basic magical law is that "as you bind, you are bound." Only a crazy person would want to be bound magically forever to a stranger for some money! A psychic reading practitioner who offers these may either be scamming for money for a spell he or she never intends to perform, or a well-meaning person who simply doesn't know enough about magic to make it work anyway.
The best way to deal with a Psychic Reading when you want a lover back is to ask, "If it is at all possible for us to get back together, what should I do in order to best promote the chances of that happening?" After that, it is even better to add the question, "If it is impossible to get back together, what should I do in order to be happy soon?" That way, you have all your bases covered in a positive way to benefit from your psychic reading.
Returning to an Ex Repeatedly: Karma or Weakness?


This Flying A Motor Deisel Fuel sign is round in shape and tan and red in color. The Flying A logo is positioned at the upper center of the sign. The logo appears withing a small red circle. Below the logo is the text that reads "Motor Deisel Fuel." Around the outside boarder of the sign is a red boarder.


Almost out of words ... :). Peak performance!! Thanks!
Thank you. I've learned what I'm sometimes up to doing ... :). Great!!
Haiku style very open kind. Good work!! I'd better get to it.
I took the liberty of promoting this Pieces. Maybe my sense of humour didn't work last weekend. Wonderful piece.


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Towns of Mexico > Chiapas > Arriaga > Agrícola Veinte de Noviembre
Agrícola Veinte de Noviembre (Chiapas)
Maps, photos and statistics of Agrícola Veinte de Noviembre, a beautiful small village of 48 inhabitants in the State of Chiapas
The town of Agrícola Veinte de Noviembre is located in the Municipality of Arriaga (in the State of Chiapas). There are 48 inhabitants. In the list of the most populated towns of the whole municipality, it is the number #25 of the ranking. Agrícola Veinte de Noviembre is at 324 meters of altitude.
Map. How to get to Agrícola Veinte de Noviembre?
Satellite photo
Photos of Agrícola Veinte de Noviembre
Opinions. Vote if you like this town
Other towns in the Municipality of Arriaga
Do you want to locate the town of Agrícola Veinte de Noviembre? You can find it at 12.0 kilometers, in direction Southesast, from the town of Arriaga, which has the largest population within the municipality. To enjoy the Agrícola Veinte de Noviembre location through satellite images, at the bottom of our webpage you have an interactive map.
The population of Agrícola Veinte de Noviembre (Chiapas) is 48 inhabitants
Population data in Agrícola Veinte de Noviembre (Chiapas)
Female Inhabitants
Male inhabitants
In the town there are 18 men and 30 women. The ratio women per men is 1.667, and the fecundity rate is 3.61 children per woman. People from outside the State of Chiapas account for 2.08% of the total population. 12.50% of the inhabitants are illiterate (11.11% of men and 13.33% of women). The average school enrollment ratio is 4.90 (5 within the men and 4.80 within the women).
Population changes in Agrícola Veinte de Noviembre since 2005
In 2005, in Agrícola Veinte de Noviembre there were 58 inhabitants. That is to say, now there are -10 people less (a variation of -17.24%). Of which there are -11 men less (a variation of -37.93%), and 1 more women (a variation of 3.45%).
Indigenous culture in Agrícola Veinte de Noviembre
0.00% of the population is indigenous, and 0.00% of the inhabitants speak one of the indigenous languages. 0.00% of the population speaks one of the indigineous languages, but not Spanish.
Unemployment and the economy in Agrícola Veinte de Noviembre
29.17% of the inhabitants (more than 12 years) are economically active (72.22% of the men, and 3.33% of the women).
Housing and infrastructure in Agrícola Veinte de Noviembre
In Agrícola Veinte de Noviembre there are 13 dwellings. 92.31% of the dwellings have electricity, 0.00% have piped water, 84.62% have toilet or restroom, 61.54% have a radio receiver, 76.92% a television, 76.92% a fridge, 46.15% a washing-machine, 15.38% a car or a van, 0.00% a personal computer, 0.00% a landline telephone, 15.38% mobile phone, and 0.00% Internet access.
Population pyramid of Agrícola Veinte de Noviembre (Chiapas)
In Agrícola Veinte de Noviembre there is a very characteristic age structure of the population, which you can see in the following population pyramid. After analyzing the demographic data of Agrícola Veinte de Noviembre, separated by men and women, and also by age groups, we can analyze how the future of the population will be in this town.
Data from the pyramid of ages of the town Agrícola Veinte de Noviembre (inhabitants year 2005)
Number of women
Number of men
Infants (0-4 years) 4 1 5
Youth (5-14 years) 11 6 17
Adults (15-59 years) 13 19 32
Elderly (60+ years) 1 2 3
>>> Click here to see more towns in the Municipality of Arriaga (statistics, photos, maps, restaurants, hotels,...) <<<
Where is Agrícola Veinte de Noviembre? How to get there? Map
How to get to the town of Agrícola Veinte de Noviembre in Chiapas? Using this map, use the controls to zoom in and out on the village and others in the vicinity to see the direct route, and to be able to plan, for example, hiking activities in Agrícola Veinte de Noviembre.
Satellite photo of Agrícola Veinte de Noviembre
Amazing satellite GPS maps of Agrícola Veinte de Noviembre, to see from space this beautiful village, as well as the surroundings of the municipality of Arriaga. Get free live access to satellite views of 2021 of Agrícola Veinte de Noviembre.
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Schools in Agrícola Veinte de Noviembre
NARCISO MENDOZA
>>> Map with all the towns within the municipality of Arriaga
>>> Click here to see more towns in the State of Chiapas (statistics, photos, maps, restaurants, hotels,...) <<<
Agua Dulce (3 inhabitants)
Azteca (La Punta) (1829 inhabitants)
Costa Bella (2 inhabitants)
Cuba (5 inhabitants)
El Palenque (- inhabitants)
El Porvenir (11 inhabitants)
La Ceiba (San Francisco) (4 inhabitants)
La Galera (- inhabitants)
La Victoria (4 inhabitants)
Las Anonas (- inhabitants)
Los Tamarindos (4 inhabitants)
San Joaquín (9 inhabitants)
San Vicente (4 inhabitants)
Santa Lucía (3 inhabitants)
Soledad León Balboa (2 inhabitants)
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Terhi Katriina Hakala (born 12 May 1962 in Viiala) is a Finnish diplomat who has been serving as European Union Special Representative for Central Asia since 2021.

Career
Hakala started working for the Ministry for Foreign Affairs in 1988. Early in her career, she was the Head of the OSCE Mission in Georgia (2007–2009) and a rotating ambassador to the South Caucasus (2004–2007). She later served as Finland's ambassador in New Delhi in India (2009–2012) and at the same time in Kathmandu in Nepal (2009–2011).

Hakala headed the Department for Russia, Eastern Europe and Central Asia at the Ministry for Foreign Affairs from 2012 to 2016. From 2016 to 2021, she served as the Ambassador of Finland in charge of the Permanent Representation in the UN in Geneva.

Other activities
 United Nations Institute for Training and Research (UNITAR), Member of the Board of Trustees (2018–2021)

References

1962 births
Living people
Ambassadors of Finland to India
Ambassadors of Finland to Nepal
Permanent Representatives of Finland to the United Nations
Ambassadors of Finland to Azerbaijan
Ambassadors of Finland to Armenia
Ambassadors of Finland to Georgia
Finnish women ambassadors


Remarks: Country estate close to town! Fill it with family or Invite your friends to Ole Miss sporting events. Perfect for entertaining with 3 large bed/bath suites, a guest house with bath and kitchenette, and an open concept kitchen and living area with wet bar and under counter ice machine. Kitchen, living room, and master bedroom open onto large screened porch. Separate TV room, formal dining room, and office. Water for the in-ground swimming pool and irrigation system provided by an on-site well. Adjoining acreage available with a fishing pond, a fenced pasture for horses, and a small barn.


The genus, Ceanothus, has over 45 species in North America. Lemmon ceanothus (Ceanothus lemmonii) is named for John Gill Lemmon (1832 – 1908) who along with his wife, Sara, collected plants throughout the American West for Asa Gray.
A native shrub that is endemic to California (only occurs in California), Lemmon ceanaothus grows from elevations of about 1,200 to 3,500 feet. Its habitat is open woodland slopes and chaparrals, disturbed areas, often along roadsides, and burned-over sites. This specimen was photographed in May along California Highway 299 south of Montgomery Creek CA (Shasta County).
Lemmon ceanothus is a low, rounded, much-branched shrub approximately 1 1/2 to 3 feet in height. The bark is grey while the twigs are hairy and grey, greenish grey or whitish.
The alternate leaves of Lemmon ceanothus are elliptical to oblong and evergreen. The leaf blades are green and waxy on the upper side and covered with hairs on the lower side. Serrulate (minutely serrated) margins and one or three prominent midveins also describe the leaves.
Lemmon ceanothus flowers are pale blue and occur in small clusters that are only 1 to 1 1/2 inches in length. These inflorescences have peduncles (stalks) as long as or longer than the flower clusters.
The somewhat triangular fruits are capsules with three chambers and three crests on the upper side containing seeds which are shiny, brown and flat when mature.
Sheep, goats and deer readily browse Lemmon ceanothus, however, cattle rarely feed on this shrub.
Gallery | This entry was posted in Shrubs and tagged Ceanothus lemmonii, Lemmon ceanothus, natural history. Bookmark the permalink.