text:
A Wiki Wiki Web is a site where everyone can collaborate on the content. Well known Wikis include
The Portland Pattern Repository at http://c2.com/cgi-bin/wiki?WikiWikiWeb.
The online encyclopaedia http://www.wikipedia.org
And of course Sensei's Library itself at http://senseis.xmp.net
A WikiWikiWeb enables documents to be authored collectively in a simple markup language using a web browser. Because most wikis are web-based, the term "wiki" is usually sufficient. A single page in a wiki is referred to as a "wiki page", while the entire body of pages, which are usually highly interconnected, is called "the wiki".
"Wiki wiki" means "fast" in the Hawaiian language, and it is the speed of creating and updating pages that is one of the defining aspects of wiki technology. Generally, there is no prior review before modifications are accepted, and most wikis are open to the general public or at least to all persons who also have access to the wiki server. In fact, even registration of a user account is often not required.
Pages and editing
In traditional wikis, every page has two representations: the form in which it is displayed (usually HTML which is rendered by a web browser) and the form in which it is edited (a simplified markup language, the style and syntax of which varies from wiki to wiki).
The formatting instructions allowed by a wiki vary considerably depending on the wiki engine that is used. Simple wikis only allow basic text formatting, whereas more complex ones have support for tables, images, formulas, or even interactive elements like polls and games.
Linking and creating pages
Wikis are a true hypertext medium, with non-linear navigational structures. Each page typically contains a large number of links to other pages; hierarchical navigation pages often exist in larger wikis, but do not have to be used. Links are created using a specific syntax, the so-called "link pattern".
Originally most wikis used CamelCase? as a link pattern, produced by capitalizing words in a phrase and removing the spaces between them (the word "CamelCase?" is itself an example of CamelCase?). While CamelCase? makes linking very easy, it also leads to links which are written in a form that deviates from the standard spelling. CamelCase?-based wikis are instantly recognizable from the large number of links with names such as "TableOfContents?" and "BeginnerQuestions?".
Creating a new page in a wiki is usually done strictly through the same process as linking to it: a link is created on a topically related page; if the link does not exist, it is in some way emphasized as a "broken" link. Following that link opens an editor window, which then allows the user to enter the text for the new page. This mechanism ensures that so-called "orphan" pages (which have no links pointing to them) are rarely created, and a generally high level of connectedness is retained.
Controlling content
Wikis generally follow a philosophy of making it easy to fix mistakes instead of making it hard to make them. Thus, while wikis are very open, they also provide various means to verify the validity of recent additions to the body of pages.
The most prominent one on almost every wiki is the so-called "Recent changes" page. It is simply a list of either a specific number of recent edits or a list of all edits that have been made within a given timeframe. Some wikis allow filtering the list to exclude edits that have been marked "minor" or which were made by automatic importing scripts ("bots").
From the change log, two other functions are accessible in most wikis: the revision history, which shows previous versions of the page, and the "diff" feature, which can highlight the changes between two revisions. The revision history allows opening and saving a previous version of the page and thereby restoring the original content. The "diff" feature can be used to decide whether this is necessary or not: A regular user of the wiki can show the "diff" of a change listed on the "Recent changes" page and, if it is an unacceptable edit, load the history to restore a previous revision. This process is more or less streamlined, depending on the wiki software that is used.
So-called "diff"-reports highlight the changes between two revisions of a page.
In case unacceptable edits are missed on the "Recent changes" page, some wikis provide additional control over content. Wikipedia was the first wiki to introduce "watchlists", a form of internal bookmarking that is used to generate a list of recent changes to a set of specific pages only. Wikipedia also allows highlighting links to pages which are below a given size, thereby making small pages, so-called "stubs", noticeable on all pages that link to them.
In extreme cases, many wikis allow protecting pages from being edited. Protected pages on Wikipedia, for example, can only be edited by so-called administrators, who can also revoke the protection.
Controlling users
While most wikis shun mandatory registration procedures, virtually all large wiki engines provide some way to restrict users who consistently violate community rules. The most common form of doing so is by banning a user from editing, which can be accomplished by banning their particular IP address. Many Internet Service Providers assign a new IP address for each login, though, so that bans can often be circumvented relatively easily.
For small wikis, a common defense against a persistent "vandal" is to simply let them deface as many pages as they want to, and to then quickly revert the pages after the vandal has left. This tactic is often considered unacceptable in the context of larger communities, where more drastic and quick action is preferred. To deal with the problem of changing IP addresses, self-expiring bans are sometimes used and extended to all IP addresses in a particular range, thereby ensuring that the vandal cannot edit pages within a given timeframe, the underlying assumption being that this is often sufficient as a deterrent.
As an emergency measure, some wikis allow switching the database to read-only mode, or letting only users registered up to a cutoff date continue editing. Generally speaking, however, any damage that is done by a "vandal" can be reverted rather quickly. More problematic are subtle errors inserted into pages which go undetected.
Most wikis offer at least a title search, if not a full text search. The scalability of the search depends highly on whether the wiki engine uses a database or not; the indexed access of a database is necessary for high speed searches on large wikis. On Wikipedia, the so-called "Go button" allows readers to directly view a page that matches the entered search criteria as closely as possible. To search several wikis at once, the MetaWiki? search engine has been created.
Wiki engines
Given the relative simplicity of the wiki concept, a large number of implementations exist, ranging from very simple "hacks" implementing only the very basic functionality to highly sophisticated content management systems. The majority of wiki engines is open source software, large projects like TWiki and the Wikipedia software are developed collaboratively. Many wikis are highly modular, providing APIs to allow programmers the development of new features without familiarity with the entire codebase.
It is hard to determine which wiki engines are the most popular, although the leading candidates would probably be the very simple to set up UseMod? wiki, TWiki, MoinMoin? and the Wikipedia software. See Wiki software for a list of wiki engines.
Wiki software originated in the design pattern community for writing pattern languages. The Portland Pattern Repository was the first wiki, established by Ward Cunningham in 1995 [1]. Cunningham invented and named the wiki concept, and produced the first implementation of a wiki engine. Some people maintain that only the original wiki should be called Wiki (upper case) or the WikiWikiWeb. Ward's Wiki remains one of the most popular Wiki sites.
In the final years of the 20th century, wikis were increasingly recognized as a promising technology to develop private and public knowledge bases, and it was this potential that inspired the founders of the Nupedia encyclopedia project, Jimbo Wales and Larry Sanger, to use wiki technology as a basis for an electronic encyclopedia: "Wikipedia" was launched in January 2001. It was originally based on the UseMod? software, but later switched to its own open source codebase which has now been adopted by many other wikis.
Today, the English Wikipedia is by far the world's largest wiki, and the non-English Wikipedias fill many of the other places. The second largest wiki, however, is Susning.nu, a Swedish language knowledge base, running the UseMod? software. The all-encompassing nature of Wikipedia has been a significant factor in its success, while many other wikis are highly specialized. Some have also attributed Wikipedia's rapid growth to the decision not to use CamelCase?.
The point is to make the Edit form simple and the FindPage search fast.
For more information read How to Use Wiki and Adding Pages. And have a look at Wiki Etiquette? before you start editing.
Most of this page was taken from http://www.wikipedia.org/wiki/Wiki.
WikiWikiWeb last edited by ArnoHollosi on August 6, 2014 - 20:26
SenseisTournament...
Sensei's Tournament Library


Compatibility is also an issue as older trucks pull newer trailers and newer trucks pull older trailers. This creates different issues for reconstruction. Load conditions, total weight, weather, environment, road and tire conditions, brake system maintenance, adjustment, capacity and capabilities must also be considered. These issues can produce conflicting data, cloud issues and render unfair judgments on the drivers/vehicles involved. Remember that since March 1999 trucks and buses with hydraulic brakes are ABS equipped and trucks with air brakes have ABS after March 1997 and air brake trailers have ABS after March 1, 1998. These are manufacture dates of the vehicles. Analyze all data carefully, identify systems properly to understand actions of the vehicles involved in the crash.


text:
Countries General
Eritrea 2017
Posted on March 8, 2021 March 8, 2021 by mathgeneral
Yearbook 2017
Eritrea. A book published during the year revealed that Eritrea's regime is involved in cruel human trafficking of Eritrean refugees. Some victims may endure torture and sexual abuse, some are executed and relatives are pressured to pay the ransom. Experts have interviewed about 200 victims and point out a group of Eritrean men with links to Eritrean government officials and military as well as criminal gangs. The book shows that human rights violations in Eritrea drive young Eritreans into exile, and individuals in the ruling party profit from smuggling and trafficking with these refugees.
According to Countryaah.com, the book "Human Trafficking and Trauma in the Digital Era" is a collaboration between exiliterate experts and professors at universities in the Netherlands and Zimbabwe.
At the beginning of the year, a UN report stated that trade relations had been discovered between the dictatorships in Eritrea and North Korea. Military communications equipment en route from North Korea to Eritrea had been discovered and stopped at sea. UN sanctions prohibit such trade with North Korea.
In April, the African Commission on Human and People's Rights condemned Eritrea's imprisonment of Eritrean-Swedish journalist Dawit Isaak, who was held for over 15 years without prosecution or judgment. The Commission demanded the release of Isaak and other imprisoned journalists in Eritrea, the country considered to have the world's worst press freedom.
Later in the year, the European Parliament passed a resolution condemning Eritrea's violation of human rights and demanding the release of Dawit Isaak.
Tensions at the disputed border between Eritrea and Djibouti increased in June, after Qatar withdrew a military observer force that has been there since 2010. According to Djibouti, Eritrean military entered the evacuated area, which is disputed. The African Union (AU) appealed to the two countries for calm and decided to send a commission of inquiry. The UN Security Council called on the countries to use peaceful means.
UN agency UNESCO decided in July to add Eritrea's capital Asmera to its list of World Heritage Sites. According to UNESCO, Asmera's architecture from the 19th and early 20th century Italian colonial rule is unique. Asmera is sometimes called Little Rome.
Former Patriarch Abune Antonios of the Eritrean Orthodox Church attended a Mass in Asmera Cathedral in July. It was the first time he had been seen in public since 2007, when he was placed under house arrest by the regime after being deprived of office. Antonios had demanded the release of political prisoners and refused banned regime opponents.
At the end of the year, protests erupted against the regime in Asmera, something unique in the heavily controlled Eritrea. Pupils at a private Muslim school were reported to have protested against the arrest of the headmaster and the government demanded a stop for religious instruction, end of ban on hijab and end of separate classes for boys and girls.
Security forces must have responded with gunfire to disperse the protesters, and according to the US embassy, protests and gunfire occurred at several locations in the city. The internet was shut down and several young men were reportedly arrested by the military. An opposition group in exile claimed that several people were shot dead and many wounded, but the regime toned down the details of violence and claimed that no one was injured.
Havana, Cuba Geography
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©2022 Countries General

redpajama_set_name: RedPajamaCommonCrawl


text:
Luffa is a genus of tropical and subtropical vines in the pumpkin, squash and gourd family (Cucurbitaceae).

In everyday non-technical usage, the luffa, also spelled loofah, usually refers to the fruits of the species Luffa aegyptiaca and Luffa acutangula. It is cultivated and eaten as a vegetable, but must be harvested at a young stage of development to be edible. The vegetable is popular in India, China, Bangladesh and Vietnam. When the fruit is fully ripened, it is very fibrous. The fully developed fruit is the source of the loofah scrubbing sponge which is used in bathrooms and kitchens.

Names
The name luffa was taken by European botanists in the 17th century from the Egyptian-Arabic name  lūf.

In North America it is sometimes known as "Chinese okra", and in Spanish as estropajo.

Uses

Fibers

The fruit section of L. aegyptiaca may be allowed to mature and used as a bath or kitchen sponge after being processed to remove everything except the network of xylem fibers. If the loofah is allowed to fully ripen and then dried on the vine, the flesh disappears, leaving only the fibrous skeleton and seeds, which can be easily shaken out. Marketed as luffa or loofah, the sponge is used as a body scrub in the shower.

In Paraguay, panels are made out of luffa combined with other vegetable matter and recycled plastic. These can be used to create furniture and construct houses.

Food

Indian subcontinent

In Hindi-speaking North Indian states, it is called torai (), and cooked as vegetable. In eastern-UP it is also called nenua. But in central/Western India, specially in Madhya Pradesh, it is called gilki (). Torai is reserved for ridge gourd and is less popular than gilki in central western India.

In Bhojpuri speaking regions it is called ghiura. Apart from fruit of the vegetable, flowers are also used as vegetable as chokha, tarua, pakoda, etc.

In Nepal and Nepali language speaking Indian states, it is called ghiraula (घिरौंला). It is popular vegetable usually cooked with tomato and potatoes and served with rice.

In Gujarat it is known as turia or turya (તુરીયા) as well as  or ghissora in the Kutchi language. It is a simple but very popular vegetable usually made with a plentiful tomato gravy and garnished with green chillies and fresh coriander. When cooked roti is shredded by hand and mixed into it, it is colloquially known as "rotli shaak ma bhuseli". Alternatively this dish is also eaten mixed with plain cooked rice.

In Bengali-speaking Bangladesh and the Indian state of West Bengal, it is known as dhudhul () and a popular vegetable. It is eaten fried or cooked with shrimp, fish, or meat.

In Assam, it is called bhul (ভুল) and is cooked with sour fish curry along with taro.

In Tamil Nadu, Luffa acutangula (ridged gourd) is called peerkangai (பீர்க்கங்காய்) and Luffa aegyptiaca / Luffa cylindrica (sponge gourd) is called nurai peerkankai (நுரை  பீர்க்கங்காய்) and are used as vegetables to make peerkangai kootu, poriyal, and thogayal. Even the skin is used to make chutney.

In Karnataka's Malenadu (Western Ghats) it is known as tuppadahirekayi, which literally translates as "buttersquash", also known as Hirekayi in Kannada. It grows naturally in this region and is consumed when it is still tender and green. It is used as a vegetable in curries, but also as a snack, bhajji, dipped in chickpea batter and deep fried. In Tulu language it is known as Peere and is used to prepare chutney and ajethna.

In Telangana, it is called beerakaya. It is used in making Dal, Fry, Roti Pacchadi, and wet curry.

In Andhra Pradesh, it is called nethi beerakaya or beerakaya. And in Assam it is called jika (জিকা, Luffa acutangula) and bhula (ভোল, Luffa aegyptiaca). It is used as a vegetable in a curry, chutney and stir fry.

In Kerala, it is called peechinga; in the Palakkad area it is particularly called poththanga and used in while bathing. It is also used as a vegetable, cooked with dal or stir fried. Fully matured fruit is used as a natural scrub in rural Kerala. In some places such as Wayanad, it grows as a creeper on fences.

In Maharashtra, India,  (ridge gourd luffa) and ghosavala (smooth luffa) are common vegetables prepared with either crushed dried peanuts or with beans.

In Manipur, India,  is cooked with other ingredients like potato, dried fish, fermented fish and served. It is also steamed and consumed or crushed () with other ingredients and served with steamed rice (chaak). Fried ones () are also favorites for many. Sebot is also eaten as a green vegetable

Other Asian cuisines
In Vietnamese cuisine, the gourd is called "" and is a common ingredient in soups and stir-fried dishes.

In China and Taiwan (where it is called , or in English, "silk melon"), Indonesia (where it is called oyong), and the Philippines (where it is called patola in Tagalog and kabatiti in Ilokano), in Timor-Leste it is also called "patola" or "batola" in Tetum and in Manipur, India, (where it is called ) the luffa is eaten as a green vegetable in various dishes.

In Japan it is called hechima () and is cultivated all over the country during summer. It is commonly used as a green vegetable in traditional dishes of the Ryukyu Islands (where it is called naabeeraa). In other regions it is also grown for uses other than food.

In Nepal it is called ghiraula and consumed as a vegetable at a young age. When it becomes ripe and dried, it is used as a body scrubbing material during bathing.

Western cuisines
Luffa is also known as "Chinese okra" in Canada and the U.S.

Other uses
In Japan, in regions other than the Ryukyu Islands and Kyushu, it is predominantly grown for use as a sponge or for applying soap, shampoo, and lotion. As with bitter melon, many people grow it outside building windows as a natural sunscreen in summer.

Role in food chain
Luffa species are used as food plants by the larvae of some Lepidoptera species, including Hypercompe albicornis.

Mechanical properties
The luffa sponge is a biological cellular material. These materials often exhibit exceptional mechanical properties at low densities. While their mechanical performance tends to fall behind manmade materials, such as alloys, ceramics, plastics, and composites, as a structural material, they have long term sustainability for the natural environment. When compressed longitudinally, a luffa sponge is able to absorb comparable energy per unit mass as aluminum foam. Luffa sponges are composed of a complex network of fiber bundles connected to form a 3-dimensional, highly-porous network.

The hierarchical structure of luffa sponges results in mechanical properties that vary with the component of sponge tested. Specifically, the mechanical properties of fiber bundles differ from those of blocks from the bulk of the sponge, which differ from those of the cross sections of the entire sponge.

Fiber-bundles
Uniaxial tensile tests of fiber bundles isolated from the inner surface provide insight this basic strut element of the luffa sponges. These fibers bundles vary in diameter from 0.3 to 0.5 mm. Each fiber bundle has a low density core region not occupied by fibers. The stress-strain response of the fiber bundles is nearly linear elastic all the way until fracture, suggesting the absence of work hardening. The slope of the linear region of the stress-strain curve, or Young's modulus, is 236* MPa. The highest stress achieved before fracture, or ultimate tensile strength, is 103 MPa. The strain at which failure occurs, or failure strain, is small at only 5%. The mechanical properties of fiber bundles decrease dramatically when the size of the hollow region inside the bundle increases.  Despite their low tensile strength, the fiber bundles have a high specific modulus of 2.07– 4.05 MPa⋅m3/kg, and their overall properties are improved when a high ratio of their cross sectional area is occupied by fibers, the fibers are evenly distributed, and there is strong adhesion between fibers.

Bulk-sponge

Block samples (height: 12.69 ± 2.35mm, width: 11.30 ± 2.88mm, length: 13.10 ± 2.64mm) cut from the core region and hoop region of the luffa sponge exhibit different mechanical behaviors under compression depending on both the orientation they are loaded in as well as the location in the sponge they are sampled from. The hoop region consists of the section of sponge located around the outside between the inner and outer surfaces, while the core region is from the sponge center. Samples from both the hoop and core regions exhibited yielding when compressed in the longitudinal direction due to the buckling of fibers. With the highly aligned fibers from the inner surface removed from the hoop region block samples, this yield behavior disappears. In general, the inner surface fibers most significant impact the longitudinal properties of the luffa sponge column followed by the circumferential properties. There is no noticeable contribution to the radial properties. Additionally, the core region exhibits lower yield stress and energy absorption (as determined by the area under the stress-strain curve) compared to the hoop region due to its greater porosity.

Overall, the stress-strain curves of block samples exhibit three stages of mechanical behavior common to porous materials. Namely, the samples follow linear elasticity for strains less than 10%, followed by a plateau for strains from 10% to 60%, and finally a stress increase associated with densification at strains greater than 60%. Segment samples created from cross sections of the entire luffa sponge (diameter: 92.51 ± 6.15mm, height: 19.76 ± 4.95mm) when tested in compression exhibit this same characteristic behavior. The three stages can be described by the equations:

 Linear elasticity region:  for
 Plateau region:  for
 Densification region:  for

In the above equations,  and  are the Young's modulus and the yield strength of the sponge material. These are chosen to best fit experimental data. The strain at the elastic limit, where the plateau region begins, is denoted as , while the strain at the onset of the densification region is .

Here  is the density of the bulk sponge  is the density of its constituent, the fiber bundle. The constant D defines the strain at the onset of densification as well as the stress relationship in the densification region. It is determined by fitting experimental data.

Dynamic loading
The mechanical properties of Luffa sponges change under different strain rates. Specifically, energy adsorption, compressive stress, and plateau stress (which is in the case of foam materials corresponds to the yield stress) are enhanced by increasing the strain rate. One explanation for this is that the luffa fibers undergo more axial deformation when dynamically loaded (high strain rates) than when quasi-statically loaded (low strain rates).

Gallery

References

External links

 Multilingual taxonomic information from the University of Melbourne

Cucurbitaceae genera
Cucurbitoideae
Fruit vegetables
Taxa named by Philip Miller

redpajama_set_name: RedPajamaWikipedia


text:
Pastinaca carvifolia är en flockblommig växtart som beskrevs av Koso-pol. Pastinaca carvifolia ingår i släktet palsternackor, och familjen flockblommiga växter. Inga underarter finns listade i Catalogue of Life.

Källor

Palsternackor
carvifolia


text:
require 'ffi_yajl'
require 'chef_zero/rest_base'

module ChefZero
  module Endpoints
    # /organizations/ORG/users
    class OrganizationUsersEndpoint < RestBase
      def get(request)
        result = list_data(request).map { |username| { "user" => { "username" => username } } }
        json_response(200, result)
      end
    end
  end
end

redpajama_set_name: RedPajamaGithub


We are overwhelmed with the generosity of our friends and neighbors both within and outside of the Ely Area. Museum staff, volunteers, Members, vendors, customers and colleagues have shown amazing support for our little museum in the pines celebrating and sharing the life and legacy of Dorothy Molter.
Thank you to Frandsen Bank & Trust of Ely, Countryside Gardens of Delano, Razor Edge Systems of Ely, Sundell Eye Associates of Virginia, Twin Metals of Ely, the Ely Veterinary Clinic of Ely, and two anonymous donors for monetary contributions to help offset the hard costs of hosting this event.
The items below will be available at the Friday, February 15 Annual Fundraising Dinner either in a silent auction (primarily) or pop-up raffles during the evening. You must be present, or have a proxy in attendance, to bid on these items. If you cannot make this event, we encourage you to help us thank the businesses, artists and organizations with your spending dollars or donations!
Most items will be in the silent auction but eight will be selected for bucket raffles – bring cash! These items are listed in no particular order.
Items are coming in up until the event and may not be posted for previewing before our dinner – it's a wonderful problem to have!
Retail: Not available for Sale!
Item 1: Crate of vintage glass bottles from Ely Bottling Works, bottles all say Ely Minnesota!
EOC/BWGS is our partner for our annual Dorothy Molter Experience: Women's Canoe Trip!
Items being added almost daily – check back often!


A new food hall opened in the Warehouse District in West Palm Beach. The 14,000-square-foot Grandview Public Market is home to Celis Produce, Clare's, Zipitios, Crema, Grace's Fine Foods, Poke Lab Eatery and more.
Johnstone Capital Partners is developing the Warehouse District, a roughly 85,000-square-foot project, owner representative Will Earl said. He declined to provide asking rents.
Other tenants include the Steam Horse Brewery with 6,300 square feet, the under construction Steel Tide Distillery with about 6,000 square feet, a squash club, barre and cycling studio and an office user. The developer also has plans for a 4,000-square-foot to 6,000-square-foot high-end restaurant.
In an ambitious and fresh take on urban renewal, the new Grandview Public Market in West Palm Beach is a chef driven market hall, taking over a mid-century warehouse building, just a short distance southwest of CityPlace. Located across from the spacious Armory Art Center, the market has a big plan – create an exciting mini hub for shopping, exercising, drinking and eating.


text:
Neural Development
Novel functions of LHX2 and PAX6 in the developing telencephalon revealed upon combined loss of both genes
Geeta Godbole1,
Achira Roy1,
Ashwin S. Shetty1 &
Shubha Tole ORCID: orcid.org/0000-0001-6584-443X1
Neural Development volume 12, Article number: 19 (2017) Cite this article
Patterning of the telencephalic neuroepithelium is a tightly regulated process controlled by transcription factors and signalling molecules. The cortical primordium is flanked by two signalling centres, the hem medially, and the antihem laterally. The hem induces the formation of the hippocampus in adjacent neuroepithelium. Therefore, the position of the hem defines the position of the hippocampus in the brain. The antihem is positioned at the boundary between the dorsal and ventral telencephalon and proposed to provide patterning cues during development.
LIM-homeodomain (LIM-HD) transcription factor LHX2 suppresses both hem and antihem fate in the cortical neuroepithelium. Upon loss of Lhx2, medial cortical neuroepithelium is transformed into hem, whereas lateral cortical neuroepithelium is transformed into antihem. Here, we show that transcription factor PAX6, known to regulate patterning of the lateral telencephalon, restricts this tissue from transforming into hem upon loss of Lhx2. When Lhx2 and Pax6 are both deleted, the cortical hem expands to occupy almost the complete extent of the cortical primordium, indicating that both factors act to suppress hem fate in the lateral telencephalon. Furthermore, the shift in the pallial-subpallial boundary and absence of the antihem, observed in the Pax6 mutant, are both restored in the Lhx2; Pax6 double mutant.
Together, these results not only reveal a novel function for LHX2 in regulating dorsoventral patterning in the telencephalon, but also identify PAX6 as a fundamental regulator of where the hem can form, and therefore implicate this molecule as a determinant of hippocampal positioning.
In development, tissues are patterned by the action of morphogens secreted by signaling centers known as "organizers." The WNT- and BMP- secreting cortical hem in the telencephalon is one such medial signaling center [1, 2]. At the lateral edge of the cortical neuroepithelium, the EGF-expressing antihem defines the boundary between the dorsal and ventral telencephalon [3].
Previously, we demonstrated that the hem is capable of organizer function, by creating embryos with multiple hems in the telencephalon, and showing that each ectopic hem induces the formation of an ectopic hippocampus [4]. The factors that act to restrict the hem to its position at the medial edge of the cortical neuroepithelium are therefore critical determinants of where the hippocampus will form in the brain. Transcription factor LHX2 is a critical suppressor of the cortical hem. In the Lhx2 null mutant, the cortical primordium cannot retain its identity, but is transformed into two alternate fates: medial cortical neuroepithelium is transformed into hem, whereas lateral cortical neuroepithelium is transformed into antihem [4, 5]. In mosaic experiments, Lhx2 null clones in the medial telencephalon display hem fate, and those in the lateral telencephalon display antihem fate, indicating a cell-autonomous requirement for LHX2 in cortical neuroepithelial cells [4]. Why loss of Lhx2 leads to two disparate fate transformations in the dorsal telencephalon is unclear.
Paired domain containing homeobox transcription factor PAX6 is required for antihem fate, which is lost in Pax6 null mutants [3]. Pax6 is expressed in a lateral(high)-medial(low) gradient, opposite to that of Lhx2 [6, 7]. We hypothesized that the presence of PAX6 may restrict the medio-lateral extent of the hem in Lhx2 mutants. Supporting this hypothesis, in the mosaic experiments performed in Mangale et al. (2008), PAX6 was lost in medial Lhx2 null patches that formed ectopic hems, but not in lateral Lhx2 null patches that formed antihem. Here, we examined medio-lateral patterning in embryos lacking both Lhx2 and Pax6, using null mutants as well as conditional knockout strategies. We find that the hem indeed expands to encompass almost the entire dorsal telencephalon when both Lhx2 and Pax6 are lost. Concomitantly, the loss of both factors appears to partially restore dorsoventral patterning that is disrupted in the Pax6 single mutant [8]. Thus, an examination of the Lhx2;Pax6 double mutant uncovers novel functions for both transcription factors, not seen upon loss of either factor alone. Our results show LHX2 to be a regulator of dorsoventral patterning in the telencephalon. PAX6 emerges as a key player in controlling the medial position of the hippocampus, because it prevents the hippocampal organizer, the hem, from being formed at lateral positions.
We used an Lhx2 null mutant line generated by targeted gene disruption [9] and the Pax6 sey/sey line which has a point mutation in the Pax6 gene creating a null allele [10] to generate the Lhx2 −/− ;Pax6 sey/sey double null mouse mutant. This mutant suffers from gross craniofacial abnormalities including an absence of external eyes, similar to the individual null phenotypes for Lhx2 −/− and Pax6 sey/sey embryos, and also lacks external nostrils similar to Pax6 sey/sey [9, 11]. A unique feature in the double null is the presence of cleft-lip/palate, indicating a combinatorial role for LHX2 and PAX6 in craniofacial development (Additional file 1: Figure S1). To our knowledge, this is the first characterization of an Lhx2;Pax6 double null mutant.
PAX6 and LHX2 together restrict medial cortical fate to the medial telencephalon
We analyzed Lhx2 −/− ;Pax6 sey/sey double mutants at embryonic day (E)12.5 with markers of medial telencephalic structures and compared the results with the expression seen in the respective single null mutants. We examined medial cortical marker Wnt8b which identifies the hem and the hippocampal primordium, and septum marker Fgf17. As expected, Wnt8b expression marks the medial telencephalic primordium in the Pax6 sey/sey mutant. In the Lhx2 −/− mutant, Wnt8b is expressed in the expanded hem, sparing some lateral tissue. In contrast, loss of both genes results in the entire dorsal telencephalon expressing medial markers, apparently sparing no lateral cortical neuroepithelium (Fig. 1). However, the double null mutant brains were fragile and the morphology made it difficult to analyze this apparent lateral-to-medial transition properly. Furthermore, the individual null mutants of Lhx2 and Pax6 are embryonic lethal [9, 10], and both genes lie on chromosome 2, which makes it difficult to obtain homozygous Lhx2 −/− ;Pax6 sey/sey double null mutants from heterozygous crosses. Therefore, we generated Lhx2 lox/lox ;Pax6 lox/lox double conditional mutants and crossed them with a ubiquituously expressed tamoxifen inducible CreER line.
Medial fates are expanded laterally upon loss of both LHX2 and PAX6. a-d E12.5 coronal sections of Control (a), Pax6 sey/sey (b), Lhx2 −/− (c), and Lhx2 −/− ;Pax6 sey/sey (d) were examined for the expression of medial cortical marker Wnt8b and septum marker Fgf17, which identify adjacent, non-overlapping regions of the medial telencephalon (open arrowheads mark the boundary between the two markers). In the double mutant, these medial markers together encompass the entire dorsal telencephalon (dashed line, d). Scale bar is 200 μm
Lhx2 and Pax6 double conditional mutants phenocopy the patterning defects in the corresponding double null mutants
We tested whether administration of tamoxifen at E8.5 to CreER;Lhx2 lox/lox ;Pax6 lox/lox animals recapitulates the results we obtained from the respective single and double null mutants by E12.5. For all experiments using Lhx2 and Pax6 single or double conditional mutant embryos, we examined the expression of the respective floxed exon(s) in each embryo in serial sections, and only used embryos which displayed extensive recombination for analysis. One example of an Lhx2 lox/lox ;Pax6 lox/lox double conditional mutant brain is shown in Additional file 2: Figure S2. Loss of Pax6 is not reported to affect patterning of the dorsomedial telencephalon [12] and indeed, the extent of Wnt8b expressing neuroepithelium appears comparable in Pax6 lox/lox and control embryos (Fig. 2a, b). In Lhx2 lox/lox embryos, Wnt8b expression appears to spare some lateral telencephalic tissue, which is presumably the antihem [4]. In the Lhx2 lox/lox ;Pax6 lox/lox double conditional mutant brains, Wnt8b expression appears to extend upto the pallial-subpallial boundary, suggesting that lateral cortical fates are missing (Fig. 2d). We therefore proceeded with these double conditional mutants for further analysis of the nature of this apparent lateral-to-medial transformation upon loss of both Lhx2 and Pax6. Furthermore, because the boundary between the dorsal and ventral telencephalon is difficult to identify accurately in the double mutant by morphology alone, we used Dbx1 expression to identify it in subsequent experiments. Dbx1, a marker of the antihem [13, 14] is expressed in a subpopulation of scattered cells in the ventricular zone of this structure [15].
Conditional deletion of Lhx2 and Pax6 from E8.5 recapitulates the lateralization of medial fates seen in the double null mutants. a-d Tamoxifen was administered at E8.5 to Control (a), CreER;Pax6 lox/lox(b), CreER;Lhx2 lox/lox(c), and CreER;Lhx2 lox/lox ;Pax6 lox/lox (d) animals, and the embryos were harvested at E12.5. Coronal sections were examined for Wnt8b expression at rostral, mid, and caudal levels of sectioning. Wnt8b expression is restricted to the medial cortical neuroepithelium in control and Pax6 lox/lox brains (a, b). In Lhx2 lox/lox brains, a small region of lateral neuroepithelium remains Wnt8b-negative (region between open arrowhead and dashed line, c). In the double conditional mutants, Wnt8b expression extends almost upto the pallial-subpallial boundary (dashed lines, c, d). Scale bar is 200 μm
The hem expands to a greater extent upon loss of both Lhx2 and Pax6 than upon loss of Lhx2 alone
Since loss of Pax6 alone did not expand medial fates (Fig. 2), we focused only on Lhx2 single and Lhx2;Pax6 double conditional mutants for further analysis. We administered tamoxifen at E8.5 to CreER; Lhx2 lox/lox single conditional mutant mice and to CreER; Lhx2 lox/lox ;Pax6 lox/lox double conditional mutant mice and harvested the embryos at E12.5. We used a set of three markers, Wnt2b, Wnt3a, and Lmx1a, to examine the extent of the hem in these mice. All three markers reveal a greater expansion of the hem upon loss of both Lhx2 and Pax6 compared with that seen upon loss of Lhx2 alone (Fig. 3). We quantified the extent of hem expansion by examining Wnt3a expression in control, Lhx2 single conditional mutants, and Lhx2;Pax6 double conditional mutants (Fig. 3a-d). We calculated the length of the hem as a fraction of the total dorsal telencephalic neuroepithelium measured up to the ventral extent of Dbx1 expression in an adjacent section (Dbx1 sections are shown in Additional file 3: Figure S3). We scored rostral, medial, and caudal levels separately and found that there was no significant rostro-caudal difference in the fractional hem length in a given mutant. As is apparent from the images, the hem is longer in Lhx2 single conditional mutants than in control brains. The key comparison of the Lhx2 single with the Lhx2;Pax6 double conditional mutants reveals that the fractional length of the hem is significantly greater when both factors are lost compared with the loss of Lhx2 alone (Fig. 3e). This indicates that PAX6 functions to restrict the lateral expansion of the hem in an Lhx2 mutant background.
PAX6 restricts the lateral extent to which the hem can expand when LHX2 is lost. (a-c; f) Tamoxifen was administered at E8.5 to Control (a), CreER;Lhx2 lox/lox(b), and CreER;Lhx2 lox/lox ;Pax6 lox/lox (c, f) animals, and the embryos were harvested at E12.5. Coronal sections were examined for the expression of hem markers Wnt2b and Lmx1a. Wnt3a was examined at rostral, mid, and caudal levels of sectioning. In each condition, the length of the hem was scored as a fraction of the total length of the dorsal telencephalic neuroepithelium measured up to the ventral extent of Dbx1 expression in an adjacent section (shown in Additional file 3: Figure S3). d cartoon illustrating the length measurement (yellow dotted line) of the hem (green). Blue dotted line indicates the length measurement of the dorsal telencephalic neuroepithelium measured upto the ventral extent of antihem (pink). e Quantification of the fractional length of the hem in control Lhx2 single conditional mutants, and Lhx2;Pax6 double conditional mutants, at rostral, mid, and caudal levels of sectioning. For each level, the single mutant hem was significantly longer than that in the control, and the double mutant hem was significantly longer than that in the single mutant or the control (**p < 0.005, ***p < 0.0005). f Adjacent sections from three different double conditional mutant embryos in which Lhx2 was incompletely recombined were examined. In each case, when Pax6 is completely removed, but Lhx2 is present in patches (open arrowheads), the hem is suppressed in Lhx2 expressing regions. A false-color overlay shows that hem (green) is not seen in patches that show Lhx2 expression (red; open arrowheads). Scale bar is 200 μm
LHX2 suppresses hem fate at the lateral extreme of the dorsal telencephalon in a Pax6 mutant background
Tamoxifen-driven Cre recombination is sometimes incomplete and results in patches of tissue that escape recombination. When we examined the lateral telencephalon of embryos that displayed complete recombination of Pax6 but had some unrecombined patches of Lhx2, it was apparent that hem only formed where both genes were lacking (Fig. 3f). That is, the presence of Lhx2 in a Pax6 mutant background was enough to suppress hem fate. This demonstrates that LHX2 is a suppressor of hem fate both medially and laterally, the latter function being revealed only in a Pax6 mutant background.
In summary, these results demonstrate that the extreme medial fate of the cortical hem can be generated at extreme lateral positions, and that LHX2 and PAX6 each suppresses hem fate. These roles of LHX2 and PAX6 are revealed only upon analysis of the double mutants, and could not have been predicted from examining either single mutant alone.
Absence of Lhx2 and Pax6 partially restores the pallial-subpallial boundary/antihem that is disrupted upon loss of Pax6 alone
Finally, we examined the pallial-subpallial boundary itself, since PAX6 is known to be a regulator of the position of this border [12, 16]. We administered tamoxifen at E8.5 to conditionally remove Lhx2 alone, Pax6 alone, or both, and harvested the embryos at E12.5. The expression of both Neurog2 and Gsx2 stops at the pallial-subpallial boundary, with Neurog2 being expressed in the pallial side and Gsx2 in the subpallial side (Fig. 4, [8]). Loss of Lhx2 does not appear to alter these expression boundaries, though it does appear to cause an overall reduction in the level of Gsx2 expression in the subpallium (Fig. 4). In the absence of Pax6, the pallial-subpallial boundary is known to shift dorsally, with Gsx2 expression seen in the lateral region of the pallium where Neurog2 expression recedes (Fig. 4; [8, 16]). This is thought to be due to cross-repression between PAX6 and GSX2 [8, 13]. However, since LHX2 appears to be required for normal Gsx2 expression, when Lhx2 and Pax6 are both lost, the expanded Gsx2 expression in the lateral neuroepithelium is no longer seen, but instead, Neurog2 is expressed there. Thus, despite the absence of Pax6, the additional loss of Lhx2 appears to restore the pallial-subpallial boundary.
The dorsal shift of the pallial-subpallial boundary upon loss of PAX6 is restored when LHX2 is also removed. a-d Tamoxifen was administered at E8.5 to Control (a), CreER;Lhx2 lox/lox (b), CreER;Pax6 lox/lox (c), and CreER;Lhx2 lox/lox ;Pax6 lox/lox(d) animals, and the embryos were harvested at E12.5. Coronal sections were examined for the expression of pallial marker Neurog2, subpallial markers Gsx2, and antihem marker Dbx1. The pallial-subpallial boundary (open arrowheads, a-d) appears to be normally positioned upon loss of LHX2 alone (b), but shifts dorsally upon loss of PAX6 alone, and Dbx1 expression is lost (c). Upon combined loss of both LHX2 and PAX6, the pallial-subpallial boundary appears to be restored to its normal position, together with Dbx1 expression. Loss of LHX2 results in lowered expression of Gsx2 in the subpallium compared with control brains (a, b, d). e Cartoons schematizing the results in a-d. f A model of the interactions between Lhx2, Gsx2, and Pax6 upon the hem and the antihem. Solid blue lines indicate regulatory functions identified in this study: LHX2 maintains Gsx2 expression levels in the ventral telencephalon, and PAX6 suppresses hem fate in the dorsolateral telencephalon. The dotted blue line indicates that regulation of Dbx1 by PAX6 is likely to be indirect. Scale bar is 200 μm
This regulation of the pallial-subpallial boundary has an intriguing effect on Dbx1 expression. GSX2 is known to suppress Dbx1 and prevent it from being expressed in the subpallium, and consistent with this, Dbx1 expands into the subpallium in Gsx2 mutants [15]. Upon loss of Pax6, Gsx2 expression occupies the region of the antihem and suppresses Dbx1 expression there [15]. Thus, the loss of Dbx1 expression in the antihem of Pax6 mutants is likely to be indirect, via GSX2. LHX2 also suppresses Dbx1 expression [4] and promotes Gsx2 expression (the current study). The expansion of Gsx2 into pallial territory upon loss of Pax6 is reversed upon the additional loss of Lhx2. The reappearance of Dbx1 in its apparently normal antihem location in the Lhx2 lox/lox ;Pax6 lox/lox double conditional mutant brain may be because both its suppressors- LHX2 or GSX2- are absent in this location.
Therefore, though Dbx1 expression is undetectable in the Pax6 single mutant, it is clear from its reappearance (albeit in an ectopic location) in the Pax6 sey/sey ;Gsx2 −/− double null mutant [15], and in an apparently normal location in the Lhx2 lox/lox ;Pax6 lox/lox double conditional mutant (this study), that Dbx1 does not require PAX6, per se, for its expression. Like Dbx1, sFrp2 expression is also lost in the Pax6 sey/sey brain [15]. However, in contrast to Dbx1, we find that sFrp2 does not reappear in the Lhx2 lox/lox ;Pax6 lox/lox double mutant (Additional file 4: Figure S4). Since loss of Lhx2 alone does not cause loss of sFrp2 expression [17], this suggests that sFrp2 critically requires PAX6 for its expression. This indicates that different molecular features of the antihem are regulated by distinct combinations of factors, underscoring the heterogeneity of this structure.
This study uncovers new roles for transcription factors LHX2 and PAX6 in patterning neuroepithelial domains in the telencephalon. LHX2 was known to suppress hem fate in the medial component of the dorsal telencephalon, but we find that PAX6 and LHX2 together suppress hem fate in the lateral component of the dorsal telencephalon as well. We discover that hem fate can indeed arise at the lateral extreme of the dorsal telencephalon, almost upto the pallial-subpallial boundary, if both PAX6 and LHX2 are removed. Therefore, this demonstrates that PAX6 plays a role in suppressing hem fate. Finally, we show that the LHX2 plays a role in regulating the pallial-subpallial boundary. This is surprising since LHX2 is expressed in a gradient in the entire telencephalic ventricular zone, and does not display an expression boundary in the lateral telencephalon. This role for LHX2 is partly due to its regulation of Gsx2 in the ventral telencephalon, which is a novel genetic interaction between these two developmental control molecules.
Our findings are summarized in the model in Fig. 4, which illustrates how LHX2 and PAX6 interact to regulate the positioning of the hem, the expression of the antihem marker Dbx1 and also where the pallial-subpallial boundary is formed. These roles for LHX2 and PAX6 are revealed only upon analysis of the double mutants, and could not have been predicted from examining either single mutant alone, thus highlighting the importance of these "classical" epistasis studies in the developing brain. More broadly, an approach that examines the functions of specific factors in the context of different mutant backgrounds may reveal unexpected spatiotemporal interactions between genes and could raise new hypotheses for the control of developmental phenomena. This may be particularly useful in understanding disorders such as autism or other neurodevelopmental diseases in which the severity of the phenotype might depend on the combinations and levels of proteins that may not appear likely to interact with each other based on standard single gene mutation studies.
All animal protocols were approved by the Institutional Animal Ethics Committee (Tata Institute of Fundamental Research, Mumbai, India) according to regulations devised by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India. The tamoxifen-inducible CreERT2 line (strain name: B6; 129-Gt(ROSA)26Sortm1(Cre/ERT)Nat/J; stock number: 004847) was obtained from the Jackson Laboratory. The Lhx2 −/− line used in this study was a kind gift from Forbes D. Porter, NIH, USA [9]. The Lhx2 lox/lox line used in this study was a kind gift from Edwin Monuki, University of California, Irvine, USA [4]. The Pax6 lox/lox line was a kind gift from David Price, University of Edinburgh [18] and the Pax6 sey/sey line was a kind gift from Anastassia Stoykova, MPI Goettingen, Germany [12].
Noon of the day of vaginal plug was designated as embryonic day 0.5 (E0.5). Tamoxifen (Sigma, MO, USA) was administered to the pregnant dams at different time points as mentioned in the text and embryos were harvested at E12.5. Control embryos were littermates with one wild-type copy of the relevant gene. The tamoxifen dosage administered was 75 μg/g body weight.
Sample preparation and in situ hybridization
Freshly harvested brains were fixed in 4% paraformaldehyde (PFA) (Sigma, MO, USA) overnight and equilibrated in 15% sucrose followed by 30% sucrose (SRL Chem, Mumbai, India). The brains were sectioned at 16 μm sections using a freezing microtome and mounted on Superfrost Plus slides (Electron Microscopy Sciences, Hatfield, PA, USA). Sections were post-fixed in 4% PFA, washed in Phosphate buffered Saline (PBS), and treated with proteinase K (Sigma, MO, USA) (1μg/ml) at 37° C for 10 mins. One more round of post-fixing and PBS washes was performed, and, the sections were incubated in hybridization buffer (5X SSC, 50% formamide, 1% SDS) containing different antisense RNA probes at 70° C overnight. Probes were prepared using a kit from Roche per the manufacturer's instructions (Roche, Mannheim, Germany). The next day, after washes with solution X (2X Saline sodium citrate SSC, 50%formamide, 1%SDS) at 70° C, followed by stringent washes with 2X SSC and 0.2X SSC at room temperature, the sections were washed with TBST (10 mM Tris-HCl, pH 7.5, and 150 mM NaCl, 0.1% KCl, 0.5% Tween-20). The slides were then incubated with alkaline phosphatase conjugated anti-Digoxigenin Fab fragments (1:5000, Roche, IN, USA) for 16 h at 4° C. The slides were then washed four times with TBST and then with developing buffer NTMT (100 mM NaCl, 100 mM Tris, pH 9.5, 50 mM MgCl, 1% Tween-20). The color reaction was performed using Nitro-blue tetrazolium chloride and 5-bromo-4-chloro-3-indolyl-phosphate (NBT-BCIP, Roche, IN, USA) as per manufacturer's instructions. The incubation was performed for 10–40 h, and terminated when the color reaction had developed satisfactorily, as assessed by the intensity of signal and low background. The reaction was stopped in Tris-EDTA (10 mM Tris-HCl (pH 7.5), 10 mM EDTA (pH 8.0) and fixed 3.7% formaldehyde (diluted in PBS from a 37% stock, Sigma for 1 h at RT. Finally, the slides were washed in PBS, dried and mounted in DPX mountant (S.D Fine Chem, Mumbai, India).
To identify unrecombined cells, an RNA probe against Lhx2 exon2/3 and Pax6 exon 5/5a/6 were made by PCR followed by in vitro transcription (Roche, Mannheim, Germany) as per the manufacturer's instructions. The primers used were as follows;
Lhx2 exon 2/3 forward: 5′ CGCGGATCCACCATGCCGTCCATCAGC 3′;
Lhx2 exon 2/3 reverse: 5′ GGCGTTGTAAGCTGCCAG 3′;
Pax6 exon5/5a/6 forward: 5′ TCACAGCGGAGTGAATCAGCTT 3′;
Pax6 exon 5/5a/6 reverse: 5′ CACTGGGTATGTTATCGTTG 3′.
For each embryo, the extent of recombination was examined by in situ hybridization for the recombined exon in one series of sections. All mutant combinations were examined in at least 4 embryos of the relevant genotype.
Image acquisition and analysis
Bright field images were acquired by Zeiss microscope Axioskop 2plus using a Nikon DS-fi2 camera. Length measurements were obtained using ImageJ software from eight hemispheres (n = 8, from 4 brains) of each genotype: control, single Lhx2 conditional mutants and Lhx2;Pax6 double conditional mutants. The hem length was measured as the length of neuroepithelium expressing Wnt3a, and dorsal telencephalic neuroepithelium length was measured from the medial edge of the hem up to the ventral extent of Dbx1 expression in an adjacent section (shown in Additional file 3: Figure S3). For each hemisphere, the ratio of the hem length to the total dorsal telencephalic neuroepithelium length was determined at rostral, medial, and caudal levels of sectioning. The mean and standard deviation (SD) were calculated, and one-way ANOVA followed by the Tukey's post-hoc test was used to determine significance. Statistical analyses were performed using Graph Pad Prism 5. Error bars in the figure indicate standard deviation (SD).
LIM-HD:
LIM homeodomain
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We thank A. Pierani (Dbx1, Fgf17), C. Ragsdale (Wnt2b, Wnt3a), E. Grove (Neurog2), K. Campbell (Gsx2), K. Millen (Lmx1a) for gifts of plasmid DNA used for generating RNA probes; L. D'souza and S. Sakhalkar for technical assistance; S. Suryavanshi and the animal house staff of the Tata Institute for Fundamental Research (TIFR) for excellent support; Edwin Monuki (Lhx2 lox/lox), Forbes D. Porter(Lhx2 -/- ), David Price (Pax6 lox/lox), and Anastassia Stoykova (Pax6 sey/sey) for the kind gift of mouse lines.
This work was supported by a grant from the Department of Biotechnology, Govt. of India (PR8681) and intramural funds from TIFR-DAE (ST), by a Wellcome Trust-Department of Biotechnology India Alliance Early Career Fellowship (GG), and Sarojini Damodaran travel award from the TIFR Endowment Fund (AS). ST is a recipient of the Shanti Swarup Bhatnagar award (Council of Scientific and Industrial Research, Government of India) and the Infosys Prize for Life Sciences (Infosys Science Foundation).
None of the aforementioned funding bodies have been involved in designing the study or collection, analysis, and interpretation of data and in writing the manuscript.
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India
Geeta Godbole, Achira Roy, Ashwin S. Shetty & Shubha Tole
Geeta Godbole
Achira Roy
Ashwin S. Shetty
GG designed the study, performed the experiments and analyses in Figs. 2, 3, and 4 and Figures S2, S3, and S4. generated the double conditional mutants; prepared the figures. AR designed the study, performed the Lhx2 −/− , Pax6 sey/sey and the double null experiments in Fig. 1 and Additional file 1: Figure S1, and contributed to writing the manuscript. ASS conceived the project, designed the study and helped to generate the double mutants, and contributed to writing the manuscript. ST conceived the project, designed the study, and wrote the manuscript. All authors read and approved the final manuscript.
Correspondence to Shubha Tole.
AR is currently at the Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
ASS is currently at the Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
All animal protocols were approved by the Institutional Animal Ethics Committee (Tata Institute of Fundamental Research, Mumbai, India) according to regulations devised by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India. (Reference Approval number: TIFR/IAEC/2012–11).
Additional file
Additional file 1: Figure S1.
Constitutive loss of both Lhx2 and Pax6 results in severe cranio-facial defects. (A,B) lateral views and (C,D) dorsal views of E12.5 heads from control (A,C) and Lhx2 −/− ;Pax6 sey/sey double mutant (B,D) embryos. A control embryo shows the presence of optic cups (black arrowhead) and nostrils (white arrowhead), while the double mutant lacks eyes (black asterisk) and displays two protruding structures in place of the nasal mass (open arrowheads), suggestive of an open or cleft palate (JPEG 965 kb)
Tamoxifen was administered at E8.5 to CreER;Lhx2 lox/lox ;Pax6 lox/lox animals and the embryos were harvested at E12.5. Near-complete recombination of Pax6 and Lhx2 is seen in a rostro-caudal series of sections adjacent to those examined for Wnt8b expression. (JPEG 807 kb)
This figure shows Dbx1 expression in adjacent sections to the images shown in Fig. 3. These images were used for measurements of the hem and the dorsal telencephalic neuroepithelium, taken upto the ventral extent of Dbx1 in adjacent sections in CreERT2; Lhx2 lox/lox (dashed lines, B,D,F) and CreER;Lhx2 lox/lox ;Pax6 lox/lox (H,J,L) embryos. Dbx1 expression in the control brain is not shown. Scale bar is 200 μm. (JPEG 856 kb)
Tamoxifen was administered at E8.5 to CreER;Lhx2 lox/lox ;Pax6 lox/lox animals and the embryos were harvested at E12.5. sFrp2 expression is not detectable in the Dbx1 expressing antihem of the double mutant embryos. (JPEG 913 kb)
Godbole, G., Roy, A., Shetty, A.S. et al. Novel functions of LHX2 and PAX6 in the developing telencephalon revealed upon combined loss of both genes. Neural Dev 12, 19 (2017). https://doi.org/10.1186/s13064-017-0097-y
Dorsoventral
Mediolateral


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from main.emails import send_follow_email, send_multifollow_email
from main.management.helpers import SendNotificationEmailCommand
from main.models import Follow, SentFollowEmail

class Command(SendNotificationEmailCommand):
    help = 'Send emails to everyone who has a new follower.'

    model = Follow
    tracking_model = SentFollowEmail
    recipient_field = 'target'
    other_field = 'user'

    send_single_email = staticmethod(send_follow_email)
    send_bundled_email = staticmethod(send_multifollow_email)

    def final_exclusion_filter(self, recipient, follow):
        assert recipient == follow.target
        if not recipient.email_on_new_follower:
            return True


text:
Q: How to insert a record into a table with a foreign key using Entity Framework in ASP.NET MVC I'm new to Entity Framework code-first. This is my learning in ASP.NET MVC, using code-first for database creation.
I have two classes:
public class Student
{
    public int StudentId { get; set; }
    public string Name { get; set; }
    public int Standard { get; set; }
    public int SubjectId { get; set; }

    [ForeignKey("SubjectId")]
    public ICollection<Subject> Subjects { get; set; }
}

public class Subject
{
    [Key]
    public int SubjectId{ get; set; }
    public string SubjectName { get; set; }
}

I'm trying to insert a Student record into the Student table, which has a foreign key SubjectId referencing the Subject table.
I'm trying it out in two possible ways:
First approach
using(var cxt = new SchoolContext())
{
    Subject sub = new Subject() { SubjectId = 202, SubjectName ="Geology" };
    Student stu = new Student() { Name = "Riya", SubjectId = 202 };
    cxt.Subjects.Add(sub);
    cxt.Students.Add(stu);

    cxt.SaveChanges();
}

Here I created a new Subject instance, which has SubjectId=202. Now when I create the Student object and assign value 202 to SubjectId, there is an Insert statement conflict. Though there is a Subject with SubjectId = 202, then why is there an insert conflict? And when I debug, I see that the navigation property Subjects is null here. I don't understand the point here.
Second approach:
using( var cxt=new SchoolContext())
{
    Student stu = new Student() { Name = "Riya" };
    Subject sub = new Subject() { SubjectId = 202, SubjectName = "Geology" };
    stu.Subjects.Add(sub);
    cxt.Students.Add(stu);

    cxt.SaveChanges();
}

But I get an a null reference exception

Object Reference not set to instance of an Object

Why is the stu.Subjects null here?
So my questions here are:

*

*What does the SubjectId in Student class mean? I.e. what does its value pertain to? Can we explicitly set it, if yes, will it refer to primary key of Subject table? If no, is it specified only for EF code conventions purpose?

*Similarly: what does navigation property role? Why is it null and when it will not be null?
My basic understanding of navigation property is that it is used to make EF determine the relationship between the two entities.
Can anyone please clarify a bit with examples which would be greatly appreciated.

A: You're basically creating a new Student, and a new Subject, in both your approaches. But from what I understand, what you're really trying to do, is create a new Student, and assign an existing Subject (with SubjectId = 202) to it - right??
The SubjectId in your Student class makes absolutely no sense in this setup - since you have a 1:n relationship between Student and Subject. You need to use that ICollection<Subject> to handle the 0:n subjects this student is enrolled in.
For that - use this code:
using(var ctx = new SchoolContext())
{
    // create the *NEW* Student
    Student stu = new Student() { Name = "Riya" };

    // get existing subject with Id=202
    Subject sub = ctx.Subjects.FirstOrDefault(s => s.SubjectId == 202);

    // Add this existing subject to the new student's "Subjects" collection
    stu.Subjects.Add(sub);

    // Add the new student to the context, and save it all.
    ctx.Students.Add(stu);

    ctx.SaveChanges();
}

That will do - a new student will be inserted into your database table, and the 1:n relationship between student and his subjects will be established.

redpajama_set_name: RedPajamaStackExchange


text:
Welcome to the Website of
Welcome Members' Area Contact Information Statement of Faith Mission Statement CSC Policies Our Services Board of Directors & Advisors Read This Before Applying Application Hints & FAQs What is Endorsement? What is Chaplaincy? Types of Chaplaincies Joining The CSC CSC Member Groups Pastoral Caregivers' Resources Military, Veterans, & their Chaplains Chaplaincy Positions Available Help Support The CSC CSC Chaplains in the News Faith & Spirituality in the News Special Needs & Requests News Chaplains Can Use CSC-ware About Neo-Pentecostals The Martin Niemöller Page Federal Chaplains Please Read Civilian Chaplains Please Read Hmmm...
What Is An Ecclesiastical Endorsement?
by David B. Plummer
Rev. 2005 & 2010
As an ecclesiastical endorsing agent for over eighteen years, I regularly receive calls from prospective chaplains who ask for "credentials" so that they can become "full-fledged chaplains." They often call with a number of mistaken notions. Some have never heard of the term "endorsement." Some think that an ecclesiastical endorsement is the same as ordination or perhaps is like a letter of recommendation. Many also think that the process of endorsement is a simple, overnight process. In truth, few chaplains and even fewer pastors understand just what an ecclesiastical endorsement is and means.
What An Endorsement Is Not
An ecclesiastical endorsement is not a letter of recommendation. Anyone or any church can write a recommendation. Only recognized ecclesiastical endorsing agencies can legally endorse. An ecclesiastical endorsement is not ordination. Only a denomination, faith group, or church has the God-given authority to ordain. The Coalition of Spirit-filled Churches (CSC) respects and recognizes the autonomous authority of its member churches and fellowship groups to ordain their clergy. Subsequently, CSC will occasionally ordain prospective chaplains ONLY on the authority and at the request of the churches and fellowship groups that it represents. As such, a prospective chaplain DOES NOT have to leave their home congregation or join a particular church or denomination in order to be endorsed with The Coalition of Spirit-filled Churches. Rather, the most natural method of affiliation is for the ordaining church or fellowship to authorize the CSC to represent them for chaplaincy purposes. Please see "Joining The CSC."
What An Endorsement Is
An ecclesiastical endorsement is a legal document that states that an ordained minister is spiritually, doctrinally, educationally, and professionally qualified to represent his/her church or faith community in a specialized setting (beyond the local congregation) ministering to all in a religiously diverse context. Simply stated, an endorsement is the document that makes a "general" minister a very specialized one — a "chaplain."
What is the CSC's Application Process?
Before the CSC will endorse a minister, he/she must complete a very thorough application process. All ministers must document their basic background information, testimony (of salvation and neo-Pentecostal beliefs and experiences), education, and professional experience. The CSC generally requires no specific educational or professional ministry background beyond that which the prospective chaplain's institution requires. Nevertheless, the CSC desires that its professional chaplains have some form of clinical education in their educational process. Next, the CSC will conduct a criminal background check with a licensed private investigator as well as a spiritual background check with the minister's pastor, ministerial colleagues, and ordaining authorities. Professional chaplaincy applicants will be then interviewed in-person by a member or friend of the CSC organization. In addition to all of the above requirements, the prospective chaplain will be instructed that he/she must have a servant's heart and a willingness to minister to all people regardless of their ethnic, religious backgrounds, and moral values. This is quite a challenge to many clergy, but if a minister desires to be a chaplain he/she must agree, in writing, to be a servant to all, without discrimination.
If a prospective minister cannot genuinely and with authenticity make such a commitment, the minister needs to choose another ministry other than chaplaincy. It is a serious integrity issue – one that is sadly not uncommon in the pastoral care community today. And religious endorsing bodies which knowingly endorse such clergy are also guilty of this professional dishonesty and breeching professional ethics. And worse, there are a few religious endorsing bodies that practice "divine deception" (lying and deceiving to manipulate people towards God – or so the deceiver believes) and actually encourage their chaplains to lie about being pluralistic for the purposes of "winning" them for the Lord. Such organizations should not be allowed to endorse; and such chaplains, when discovered, should be discredited as a professional and removed from their office.
The Significance of An Endorsement
An endorsement is only good for a specific period of time, for a specific institution. Endorsement means that a minister is on temporary "loan" from their church to an organization. At almost any time, for a variety of reasons, a chaplain can have his/her endorsement withdrawn and the minister quickly becomes a "non-chaplain." Further, if the chaplain does not perform to the high standards of chaplaincy or is guilty of ethical breech or felonious activity, he/she is likely to find their endorsement non-renewed, if not "pulled" (prematurely terminated) for cause. Ultimately, endorsement links all chaplains to their ordaining churches and faith communities in matters of accountability and spiritual oversight. Thus, chaplains are continuously accountable to their sponsoring church, ordaining authority, the endorsing agency, and to the institution of which they are a part.
Since an endorsement is a very serious legal document, endorsing agencies are charged by God, the government, and various professional organizations to credential only their very finest clergy as chaplains. To date, there are over 150 federally-recognized endorsing agencies, representing all major religions, denominations, and faith groups.
For a good article on this topic, please visit http://plainviews.healthcarechaplaincy.org
and read 'The Challenges of Endorsers and Endorsements,'
or click here to download PDF.
The Coalition of Spirit-filled Churches, Inc.


NEW YORK, June 12, 2014 – Trickle Up has been selected as the recipient of the InterAction 2014 Disability Inclusion Award, recognizing its long commitment to serving people with disabilities as part of the organization's work helping the poorest and most vulnerable take the first steps out of extreme poverty.
Trickle Up also received the Disability Inclusion Award in 2009, making it the only InterAction member to win it twice. Other recent recipients include World Vision, Habitat for Humanity, International Rescue Committee, and the International Federation for Electoral Standards. InterAction represents more than 180 US-based development and relief organizations.
"We are proud to recognize Trickle Up as this year's recipient of InterAction's Disability Inclusion Award. The award honors InterAction members striving to ensure that everyone – including individuals with disabilities – has the opportunity to build a better future for themselves and their families," said Samuel A. Worthington, President and CEO of InterAction.
"Working with families affected with disabilities is a core part of our commitment to support people who are marginalized and live in extreme poverty to develop the skills and confidence to become active and informed drivers of their own development," said Bill Abrams, President of Trickle Up. "It is a great honor to be selected by our peer international organizations for the Disability Inclusion Award." The award will be presented at the InterAction Forum on June 11-13 in Washington, D.C.
Founded in 1979, Trickle Up is focused on the "ultrapoor," people who live below the $1.25/day consumption standard established by the UN as a threshold for extreme poverty. Trickle Up provides a system of business training, seed capital grants and savings programs to help families increase their income, build assets and save for the future, and develop planning skills and confidence that will help them start on a sustainable path out of poverty. Approximately 15% of Trickle Up's participants have a disability or live in a family directly affected by disability. Trickle Up operates programs in Central America, West Africa and India, as well as a technical assistance program in Egypt, Costa Rica and Ecuador.
In 2013, TU completed a three-year USAID-funded project in Guatemala serving people with disabilities, as well as helping four community-based poverty agencies and a municipal government program extend services to people with disabilities. As part of the project, Trickle Up published Disability, Poverty and Livelihoods, a guide to lessons learned during the project and suggestions for effectively incorporating people with disabilities in livelihood development programs. This is available in English and Spanish and has been shared with disability networks and economic development networks. Trickle Up has also led a major disability program in Mali, funded by USAID.
To help promote inclusive programming to other organizations, Trickle Up will host No Limits: An Expert Panel on Global Poverty and Disability in New York in June 2014, featuring Judith Heumann, Special Advisor for Disability Rights at the U.S. Department of State, Charlotte McClain-Nhlapo, Coordinator for Disability and Inclusive Development at USAID and Jo Sanson, Trickle Up's Director of Monitoring, Evaluation and Research.


Socialising your puppy at a young age is crucial, as their window for readily accepting new experiences starts to close at around 16 weeks. It is important therefore, that you make the most of early puppyhood and pack in as many good experiences during this time as possible. One of the best ways for puppies to build their knowledge of dog communication systems is for them to attend well-run puppy socialisation parties and training classes. Our puppy parties are run by Louise Williamson. Louise is a receptionist at our Chichester clinic and also runs puppy training classes in Chichester and Emsworth. Our puppy parties are run at Denmead, Havant, Emsworth, Chichester, Barnham and Hilsea.
Our puppy patients are invited to attend our puppy parties once they have started their vaccination course. All puppies that complete the 2 week socialisation receive a certificate and a rosette!
Laparoscopic, or "key hole", surgery is seen as gold standard in human medicine and is now making the transition to the veterinary world. It is well documented that it causes fewer complications and less post-operative pain in people, compared to traditional surgery, and we are now seeing data in animals which supports this.
This procedure can offer a quicker recovery time often allowing dogs off the lead and running around three days after surgery. The wounds are also smaller meaning your pet is less likely to lick them and cause complications.
The procedure is performed by a small needle being placed into the abdomen which is then used to inflate the patient with carbon dioxide. This creates a space for the camera to be placed and gives the surgeon room to move instruments around. Three small tubes are then placed into the abdomen which act as ports for instruments to pass down and through which the ovaries can be removed. The wounds are small and are closed without external stitches.
Traditionally in the UK we have performed ovariohysterectomy where the ovaries and the whole of the uterus are removed. In mainland Europe and the US ovariectomy has always been used whereby the ovaries are removed but the uterus is left in place. The rationale in the UK for removing everything was to eliminate risk of pyometra, an infection in the uterus. This has now been disproven, as pyometra does not occur when the ovaries are removed and this data shows that we only need to perform an ovariectomy. Therefore in laparoscopic surgery only the ovaries are removed which further reduces tissue handling and trauma to the patient.
The procedure is highly successful with great results following surgery however as with all procedures there are risks and potential complications. If at any point the surgeon is unhappy with how the procedure is going, i.e. due to equipment failure, abnormal bleeding etc, the decision may be made to convert to an 'open' surgery. This decision would always be made with the safety of the patient in mind.
Here at Downland Veterinary Group we welcome patients in all shapes and sizes and over the years we have developed a firm foundation of exotic animals under our care. Exotic pets have become more popular in recent years and our dedicated team have been enhancing their knowledge and keeping up to date in the ever developing exotic medicine field by attending regular courses taken by specialists from around the globe.
Our experienced team routinely carry out comprehensive work ups for exotic animals using diagnostic equipment and techniques on site in addition to being able to send samples off to our external laboratory for further analysis.
If you would like to book up a consultation for your exotic pet then please make an appointment at our Emsworth clinic with either Dean or Gus who will be more then happy to investigate any problems they are experiencing.
Please call 01243 377141 for more information.
It is imperative to keep your avian pets in optimal condition. Due to birds' rapid metabolic rate they can deteriorate quickly if they become ill and will likely need rapid supportive treatment. It is not uncommon for us to see avian patients presented to us as an emergency. To help with prevention of disease and promote early detection, we recommend yearly check-ups and health screening. In addition to yearly screens, if you have any concerns about your pet bird's health, then we would prefer to see them too soon rather than too late.
Here at Downland Veterinary Group we have the facilities to perform a wide range of therapy for your avian pets including extensive diagnostics, emergency care and overnight hospitalisation.
Very few reptiles are native to the UK and so the vast majority kept as pets need to be provided with an environment that replicates that of their natural habitat. In recent years there have been large steps taken forward in the world of herpetology allowing for improved husbandry and veterinary care.
At Downland Veterinary Group, we aim to optimise our reptilian patient care by constantly updating our veterinary knowledge to maintain us at the forefront of diagnostic and treatment techniques.
Small mammals such as ferrets, rabbits, hamsters, skunks and pigmy hedgehogs are also encompassed under exotic veterinary medicine. Like other exotic animal care, husbandry, nutrition and regular health checks are paramount in maintaining their optimal health. They can present with a number of conditions which need to be addressed early to allow rapid treatment and recovery.
The exotic animal team at Downland Veterinary group are primed to provide rapid and precise care for your small mammal companions.
Endoscopy is a process of using small cameras to examine the internal structure of certain hollow body parts. This non-invasive technique can allow visualisation or areas that would require, in some cases, radical surgery to access otherwise. The cameras can be used to examine and record the appearance of structures, to obtain samples via biopsy or washes or to remove foreign bodies.
We now offer arthroscopy (allowing visualisation of a joint without surgery to open it) and also laparoscopic surgery whereby body cavities (such as the abdomen) can be examined and surgery performed through 'key hole' incisions.
With the range of exotic species we see, it is not unusual for our exotic vet Dean to be using the cameras in some unusual animals!
Ultrasound is a non-invasive (and therefore non-painful) way of imaging which we find invaluable in the work-up of a lot of medical and surgical cases. We have had many years' experience with ultrasound at the Bognor Regis surgery (Annette Moyart has 10 years' experience). We find it a very useful tool to obtain definitive diagnoses and prognoses in a wide range of cases. Ultrasound ensures that we get the most information possible, with the least risk to the patient and guides prompt treatment. We provide pain relief if the patient is uncomfortable but they remain conscious throughout the procedure. The patient lies on a nice comfortable bed and is held gently by nurses. We clip some hair over the region we are imaging and to improve contact of the ultrasound probe with the skin, gel is applied to the skin.
These cases are often very unstable (weak and collapsed or having breathing difficulty), so ultrasound has the advantage of being non-invasive, allows rapid assessment and it doesn't necessitate anaesthesia which could be dangerous in these individuals.
These cases are often of a more chronic nature; such as weight loss, vomiting, diarrhoea, abdominal masses, abnormal urination or ongoing discomfort. They have often been unresponsive to standard treatment eg a course of antibacterials of bacterial cystitis in a dog. There has often been prior investigations such as blood or urine tests and radiographs, but a definitive diagnosis or prognosis has not been reached. We have a lot of experience in the investigation of a wide range of medical cases involving internal organs such as liver, spleen, pancreas, gut and urinary system including prostate disease. We routinely perform ultrasound-guided biopsies, cystocentesis, thoracocentesis and abdominocentesis. The fine needle aspirates are often submitted to a specialist cytologist to obtain a definitive diagnosis.
Ultrasound can also be used in a wide variety of other cases; including assessment of skin masses or, hernias and for the presence of free fluid in a body cavity. Please contact us if you are unsure if a case could benefit from ultrasound imaging.
DVG's orthopaedic service is run at the Emsworth surgery by Fabio Cabriolu and Gus Nieves. We offer a wide range of services including TTA and lateral suture for cruciate ligament repair, luxating patella surgery, lameness work-up, fracture repairs and arthrodesis.
We also do arthroscopy, where by small cameras can be placed into joints to help diagnose and treat certain conditions.
At Downland Veterinary Group we are very proud of our nursing team. Our team consists of registered veterinary nurses or RVNs, student veterinary nurses, and animal care assistants. We follow the Royal College of Veterinary Surgeons, RCVS, code of conduct to ensure that all members of the nursing team only undertake skills that they have undergone appropriate training in, and have been deemed competent. Different members are easily recognisable by the colour of their uniform. All of our nursing team are a very crucial part of the team at DVG. Without them our days would simply not run smoothly.
During working hours they are ensuring that the clinic is clean and tidy and ready to welcome patients. They provide care in kennels for all the ill pets and those recovering from surgery. They assist in theatre and monitor anaesthetics whilst the vets are operating. They also run the in-house laboratory and ensure that consultations are running smoothly by providing assistance there. In many cases you will see a member of the nursing team if your pet is coming in for an operation and they will admit them and go through the pre-operative procedures with you. They also ensure that all of the medications are stocked up.
If you would like to see someone about any of these services, please do contact reception who can advise about making an appointment for you.


Beanie Sigel becomes the latest former Roc-A-Fella artist to go at the former boss (I'm still waiting for Memphis Bleek to grow a pair and stop being Hov's hype man...not that there's anything else there for him). I'm not entirely sure what to think about the situation, but as a bonus, I've included his very dope guest appearance on OB4CLII.
Bonus - Raekwon feat. Beanie Sigel & Blue Rasberry - "Have Mercy"


text:
Our Mission, Vision, Values
David and Olive Pretty Archives
Bronze Medallion
Hilary M. Weston Award
Prerequisite Policies
Volunteer Code of Conduct
Governor's Awards Gala
a brief history of resuscitation
The Lifesaving Society's 1910 version of Handbook of Instruction cites the year 1650 as the date of the first known instances of resuscitation on a drowning victim. In the late 1760's a Society was formed in Amsterdam to assist drowning victims and provide resuscitation.
A similar group was proposed for England in 1773, but did not initially take off. The need for action on the Thames was taken up Dr. Hawes. Anyone who spotted a drowning victim in the river was requested by Hawes to rescue the person from the water. Victims were to be brought to the shore between the Westminster and London bridges for resuscitation.
The victim had the pipe of a pair of bellows inserted into one nostril, the other nostril and mouth were closed. Air was forced into the lungs through the bellows and forced out by pressure placed on the chest.
In 1910 candidates were required to use the Schafer Method, or "prone-pressure" method, of resuscitation, where victims were laid face down and compression applied to the middle of the back. This was done to expel air from the lungs, upon release of pressure on the back the air would return to the lungs. Having the victim facedown was also done to allow any water, froth or vomit to leave the victims mouth easily.
In 1952 the Shafer method was replaced by the Holger-Neilson method, which was similar in purpose and style. The overall goal was to drive water from the lungs of a drowning victim using pressure applied to the upper back of a facedown victim.
Just seven years later in 1959 the Direct method, or "mouth-to-mouth" was adopted by the Society. This is still the basis of current CPR methods used today.
Resuscitation was taught to Bronze Medallion candidates. Similar to current instruction candidates were given background and theoretical information. Diagrams of chest cavity and heart were used as well as general descriptions of anatomy and physiology behind circulation and respiration.
Click here to see pages from the 1910 Handbook of Instruction.
Practice drills were used to prepare candidates to use the resuscitation method of the day if need be. Click here to see practice drills.
Throughout the years many methods of resuscitation have been used. Through research, debate and practice these methods have been adapted to create the modern method of CPR we use today.
An Overview of resuscitation methods
Marshall-Hall (developed in 1856)
Rescuer positioned at the top of the head, leaning over the victim
Victim placed facedown and rolled from side to side, pressure applied between the shoulder blades
Victim rolled 15 times per minute
Silvester (introduced in 1857)
Rescuer kneeling above the head of the victim
Victim positioned face-up with both arms above the head (to inflate the lungs)
Arms folded and pressed against the sides of the chest (to deflate the lungs)
The sequence continues
Howard (presented in 1869)
Victim laid on the back
Lower ribs pressed with rescuers hands to expel air from the lungs
Upon release of pressure lungs fill with air
Schafer (adopted in 1903)
"Prone-pressure method"
Rescuer knelt beside a facedown victim
Pressure applied with two hands to the upper back, the heel of each hand pressing on one of the victims shoulder blades
Researched and compared existing methods to form the Schafer method
Adopted by the Society because of simplicity and focus on drowning victims
Holger-Neilson (developed in 1952)
Pressure applied to the upper back of a face-down victim
Designed to force water out of the lungs
Direct method (adopted in 1959)
"Mouth-to-mouth" was chosen as the Society's preferred method of resuscitation
Face-up victim, unlike many previous methods
Tight seal around the mouth provides more oxygen to victim
Current CPR and resuscitation techniques are based on this method
Click here to for information and diagrams from our 1959 Annual Report regarding Artificial Respiration.
Today the Society's resuscitation methods are based on recommendations from the International Liaison Committee on Resuscitation (ILCOR). Every two years ILCOR recommends research-based changes to improve resuscitation. The Society's instructors are re-trained in the new methods and all relevant Society literature is revised on a five-year basis. Our most recent changes were in 2010 - compare our current resuscitation method with methods from the past.
For children under 5 years, being alone near water was a factor in 61% of drownings and a momentary absence/lapse of caregiver attention occurred in 53% of drownings.


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"Plentiful standard features; decent-size third-row seat, sporty handling; optional fuel-efficient four-cylinder; optional punchy V6; long warranty." -Edmunds.com. Great Gas Mileage: 25 MPG Hwy.


Jay McInerney, author, socialite, wine expert, and icon of the 80's NYC nightlife scene needed a new website. His current site was brooding but boring.. with not much to connect the fan/visitor to the legend. KRD designed his new site to be insider-ish, interactive and immediate including (as-they're-tweeted) Tweets on his home page; a graphic timeline to click and drag through Jay's visual biography; and the author's own notes and comments on each of his books. The site was built so that Jay could manage his own blog posts and his publicist could add new events and speaking engagements on his Appearances page as they happen. We also set Jay up on an email platform so that his fans could sign up and receive McInerney's latest posts in their email.


Many people ask whether they should hire a Texas tax lawyer to represent them before the Internal Revenue Service. The answer depends on who you ask. The IRS will tell you that you don't need a tax lawyer. And they have a very good reason to suggest this. The IRS wins when you handle your tax matter on your own. Why? When you have an experienced tax attorney handling your IRS problems, you have an advantage over the IRS agent who rarely knows the intricacies of the tax law and invevitably will attempt to violate your rights as a taxpayer. A Texas tax lawyer will use the law to your advantage and hold the IRS to the same standard they attempt to hold taxpayers.
The Scammahorn Law Firm has been handling IRS problems for taxpayers all across the State of Texas for nearly 20 years. Our clients are assured their rights as taxpayers are being exercised through appeals of tax liens, bank and wage levies, and offers in compromise. The Scammahorn Law Firm uses the court system when necessary to sue to the Internal Revenue Service to assure they are following the law, something the IRS seems to rarely do.
If you have an IRS problem, whether an employment tax issue, personal tax issue, unfiled tax returns, or fighting an IRS lien or property seizure, you need a Texas tax lawyer on your side.
Call the Scammahorn Law Firm today to put an end to your tax problems.