R.

            _numbers.Add(0);
            AddDomainEvent(new TestDomainEvent(0, this));

            // Here you usually return what the domain business model is for, for example, if you verify a payment here, you 
            // would create the payment and after adding it to the collection and create and add the domain event, you return
            // the object.
            return new Test();
        }
    }
}
<?php
/**
 * RedUNIT_Plugin_Export
 *
 * @file    RedUNIT/Plugin/Export.php
 * @desc    Tests export functions for beans.
 * @author  <NAME> and the RedBeanPHP Community
 * @license New BSD/GPLv2
 *
 * (c) G.J.G.T. (<NAME> and the RedBeanPHP Community.
 * This source file is subject to the New BSD/GPLv2 License that is bundled
 * with this source code in the file license.txt.
 */
class RedUNIT_Plugin_Export extends RedUNIT_Plugin
{
	
	/**
	 * Test export.
	 * 
	 * @return void
	 */
	public function testExport()
	{
		// Export with parents / embedded objects
		$wines = R::dispense( 'wine', 3 );

		$wines[0]->name = '<NAME>';
		$wines[1]->name = 'Chardonnay';
		$wines[2]->name = 'Malbec';

		$shelves = R::dispense('shelf', 2 );

		$shelves[0]->number = 1;
		$shelves[1]->number = 2;

		$cellar = R::dispense( 'cellar' );

		$cellar->name     = '<NAME>';
		$cellar->ownShelf = $shelves;

		$shelves[0]->ownWine   = array( $wines[0], $wines[1] );
		$shelves[1]->ownWine[] = $wines[2];

		$id = R::store( $cellar );

		$wine = R::load( 'wine', $wines[1]->id );

		$list1 = R::exportAll( array( $wine, $shelves[1] ) );
		$list2 = R::exportAll( array( $wine, $shelves[1] ), TRUE );

		asrt( $list1[0]['name'], 'Chardonnay' );

		asrt( isset( $list1[0]['shelf'] ), FALSE );
		asrt( isset( $list1[0]['shelf_id'] ), TRUE );
		asrt( isset( $list1[0]['shelf']['cellar'] ), FALSE );

		asrt( $list2[0]['name'], 'Chardonnay' );

		asrt( isset( $list2[0]['shelf'] ), TRUE );

		asrt( intval( $list2[0]['shelf']['number'] ), 1 );

		asrt( isset( $list2[0]['shelf']['ownWine'] ), FALSE );
		asrt( isset( $list2[0]['shelf']['cellar'] ), TRUE );
		asrt( isset( $list2[0]['shelf']['cellar']['name'] ), TRUE );
		asrt( isset( $list2[0]['shelf_id'] ), TRUE );

		asrt( intval( $list1[1]['number'] ), 2 );

		asrt( isset( $list1[1]['ownWine'] ), TRUE );
		asrt( isset( $list1[1]['cellar'] ), FALSE );
		asrt( isset( $list1[1]['cellar']['name'] ), FALSE );

		asrt( intval( $list2[1]['number'] ), 2 );

		asrt( isset( $list2[1]['ownWine'] ), TRUE );
		asrt( isset( $list2[1]['cellar'] ), TRUE );
		asrt( isset( $list2[1]['cellar']['name'] ), TRUE );

		R::nuke();

		$sheep = R::dispense('sheep' );

		$sheep->aname = 'Shawn';

		R::store( $sheep );

		$sheep = ( R::findAndExport('sheep','aname =? ', array( 'Shawn' ) ) );

		asrt( count( $sheep ), 1 );

		$sheep = array_shift( $sheep );

		asrt( count( $sheep ), 2 );

		asrt( $sheep['aname'], 'Shawn' );

		R::nuke();

		testpack( 'Extended export algorithm, feature issue 105' );

		$city   = R::dispense( 'city' );
		$people = R::dispense( 'person', 10 );

		$me = reset( $people );

		$him = end( $people );

		$city->sharedPeople = $people;

		$me->name ='me';

		$suitcase = R::dispense('suitcase' );

		$him->suitcase = $suitcase;

		$him->ownShoe = R::dispense('shoe', 2 );

		R::store( $city );

		$id = $him->getID();

		$data = R::exportAll( $city );

		$data = reset( $data );

		asrt( isset( $data['sharedPerson'] ), TRUE );
		asrt( count( $data['sharedPerson'] ), 10 );

		$last = end( $data['sharedPerson'] );

		asrt( ( $last['suitcase_id'] > 0 ), TRUE );

		$data = R::exportAll( $him );

		$data = reset( $data );

		asrt( isset( $data['ownShoe'] ), TRUE );

		asrt( count( $data['ownShoe'] ), 2 );
		asrt( count( $data['sharedCity'] ), 1 );
	}
}
The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination
Summary testosterone analogue 7α-methyl-19-nortestosterone, which has been developed for long-term male contraception and androgen replacement therapy in hypogonadal males and does not stimulate prostate growth, also efficiently promoted myelin repair. These data establish the efficacy of androgens as remyelinating agents and qualify the brain androgen receptor as a promising drug target for remyelination therapy, thus providing the preclinical rationale for a novel therapeutic use of androgens in males with multiple sclerosis.
- myelin
- remyelination
- multiple sclerosis
- testosterone
- androgen receptor
Introduction
The past decade has offered significant advances in the treatment of multiple sclerosis with the development of new immunomodulatory drugs, anti-inflammatory agents and neutralizing antibodies (Kieseier and Stuve, 2011). However, although reducing CNS lesions by modulating immune attacks remains the first-line therapy for multiple sclerosis, there is an urgent need for additional treatments to promote repair of the damaged myelin. There is indeed ample evidence that the failure of myelin repair is a major contributing factor to the outcome of multiple sclerosis and to its evolution into a progressive disorder (Martino et al., 2010). A therapeutic option, which has recently gained much interest, would be to boost the endogenous capacity of the brain to repair myelin damage. Myelin can indeed be self-repaired during the early stages of multiple sclerosis, but with the progression of the disease, the capacity of myelin recovery decreases, possibly because of the failure of oligodendrocyte precursor cell recruitment and differentiation (Franklin and ffrench-Constant, 2008; Kuhlmann et al., 2008; Piaton et al., 2009). The remyelination of axons indeed requires the generation of new oligodendrocytes from oligodendrocyte precursor cells.
Testosterone has a beneficial influence on experimental autoimmune encephalomyelitis, a widely used disease model for the immune-mediated and inflammatory aspects of multiple sclerosis (Palaszynski et al., 2004). It is likely that the immunomodulatory, anti-inflammatory and neuroprotective actions of testosterone contribute to this effect (Liva and Voskuhl, 2001; Malkin et al., 2004; Page et al., 2006; Fargo et al., 2009). These observations were the basis for a clinical trial in which the effects of testosterone supplementation were studied in males with relapsing-remitting multiple sclerosis for 1 year. The outcomes, anti-inflammatory effects and improved cognitive performance were encouraging, and additional preclinical investigations on the actions of testosterone may provide support for further clinical trials (Sicotte et al., 2007; Gold et al., 2008).
Whether testosterone therapy also promotes myelin repair has not been investigated. Addressing this important question requires an experimental model that induces the demyelination of axons in a highly reproducible manner and allows accurate quantification of their remyelination. Cuprizone-induced demyelination of brain white matter tracts is a well-characterized and widely accepted animal model that fulfils these requirements and