Of more practical interest is Dr Green’s idea that it is epigenetics and not genetics that makes a cancer cell.  If this is true, then an entire anti-cancer industry based on the idea of mutations being the root cause of cancer is misguided.

        We expense research and development costs to operations as incurred. We defer and capitalize nonrefundable advance payments we make for research and development activities until the related goods are received or the related services are performed.

(a) Schematic diagram of cloned rat putative promoter region of miR-322, stretching from upstream 1000 bp. The position of the putative HRE matching the core sequence (A/G)CGTG is labeled in box, between two functional CACAG elements (P1k). A mutant promoter was constructed with the sequence as shown below (P1k-m). (b) Luciferase reporter assays of miR-322 promoter activity with both wild (pGL4-P1k) and mutant constructs (pGl4-P1k-m) in the presence or absence of CoCl2 (200μM) (left panel); Under these conditions, the protein levels of HIF-1α and HIF-2α were stabilized after CoCl2 treatment in the cells as determined by western blot analysis and normalized to β-actin levels (right panel). (c) miR-322 promoter activity assessed by luciferase reporter assay after CoCl2 treatment was diminished by HIF-1α knockdown. Cells were transduced with shRNA targeting HIF-1α (shHIF-1α) or HIF-2α (shHIF-2α) and miR-322 promoter activity was determined in the luciferase reporter assay after transfection of wild type and mutant constructs and CoCl2 treatment (left panel) as described under Methods; Control (sh-Con) or HIF-1α/-2α shRNA-transfected cells were harvested for protein analysis by western blot to determine knockdown specificity (right panel); *p < 0.05 compared with sh-Con. (d & e) A7r5 cells were transfected with recombinant adenoviruses expressing oxygen-dependent degradation domains (ODDD-wt) or mutated ODDD (ODDD-mut) under normoxic conditions. The influence on the miR-322 promoter reporter activity (d) and the endogenous expression levels (e) of miR-322 were determined by real-time PCR. All the bar plots represent means ± SD. *p < 0.05, **p < 0.01,compared with ODDD-mut. (f) Western blot for HIF-1α and HIF-2α in ODDD–transfected A7r5 cells after 24 hours. β-actin served as loading control. The full-length blots with these antibodies were presented in supplementary Figure S3. All gels have been run simultaneously under the same experimental conditions. (g) HIF-1α dynamic binding on the HRE site (−797 to −793) on the miR-322 promoter. ChIP assays were performed with indicated antibodies in the absence or presence of CoCl2 (left), or transfected with ODDD-wt or ODDD-mut (right) as described under Methods. Representative gel with input lanes showing products after PCR amplification and before immunoprecipitation.

        Agreements through which we license patent rights may not give us sufficient rights to permit us to pursue enforcement of our licensed patents or defense of any claims asserting the invalidity of these patents (or control of enforcement or defense) of such patent rights in all relevant jurisdictions as requirements may vary.

American Oriental Bioengineering Inc. (NYSE:AOB ) is a pharmaceutical company dedicated to improving health through the development, manufacture and commercialization of a broad range of prescription and over the counter products.

All the animal experimental protocols were approved by the Animal Experimental Ethics Committees of the Third Military Medical University and were performed in accordance with the guidelines of The Third Military Medical University. P311−/− mice were a kind gift from Professor Gregory A Taylor12. P311+/+ C57BL/6 mice (Charles River Laboratories) were purchased from Beijing VITAL RIVER Company and raised at the Animal Institute of Daping Hospital, The Third Military Medical University. Ten P311−/− mice and ten age-matched P311+/+ mice (males; 6–8 weeks old; body weight, 18 to 20 g) were used for the UUO operations. UUO surgeries were performed as previously described47,48,49. Briefly, mice were anesthetized by intraperitoneal injection of 1% sodium pentobarbital (10 μl per gram body weight). In the UUO groups, the left ureter was exposed through a left-flank incision on the back and ligated twice with a 4-0 silk suture. A cut was made between the ligatures to prevent a retrograde urinary tract infection. Sham groups were subjected to a similar procedure without ureteral ligation. After 7 days, the mice were sacrificed. The time point was chosen on the basis of our pre-experiments and the previous study demonstrating that at 7 days, the obstructed kidneys revealed marked tubular dilation and atrophy, interstitial matrix deposition50. Subsequently, both kidneys were removed, cut transversely, and either fixed in 4% paraformaldehyde for histopathological studies or snap-frozen in liquid nitrogen for western blot analysis.

        Once marketing approval has been granted, an approved product and its manufacturer and marketer are subject to ongoing review and extensive regulation. We, and any future collaborators, must therefore comply with requirements concerning advertising and promotion for any of our product candidates for which we or they obtain marketing approval. Promotional communications with respect to prescription drugs are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved labeling. Thus, we and any future collaborators will not be able to promote any products we develop for indications or uses for which they are not approved.

Ceragenix Phamaceuticals Inc. (OTCBB: CGXP ) Ceragenix Pharmaceuticals, Inc. is a medical device company focused on infectious disease and dermatology. The Company has two base technology platforms; Ceragenins for treatment of infectious disease and Barrier Repair for the treatment of dermatological disorders including atopic dermatitis, neonatal skin disorders and others.

In in-vitro and in vivo studies, Aramchol down regulates the SCD1 enzyme, an enzyme recognized as playing an important role in the metabolism of fatty acids. The SCD1 enzyme is essentially the gateway that regulates the use and storage of fat in the body by converting saturated fatty acids to monounsaturated fatty acids. Experimental animal studies showed that complete inhibition of the SCD1 enzyme protects against diet-induced obesity, hepatic steatosis, or fatty liver, and insulin resistance by instructing the body to use, rather than store, all fatty acids. However, various animal studies have indicated that such complete SCD1 enzyme inhibition has mechanism based serious side effects, such as atherosclerosis, and eye and skin disorders. As observed by us in our pre-clinical and clinical studies performed to date, and subsequently published in the European Journal of Gastroenterology and Hepatology and Archives of Medical Research in 2008 and 2010 respectively, one of Aramchol’s unique characteristics is that it down regulates the SCD1 enzyme but does not inhibit it completely – a partial effect. To date, side effects that have been observed in animals with knock out of SCD1 have not been observed in our toxicology and clinical studies.

Rat PASMC cells were isolated from pulmonary arteries of Sprague-Dawley rats. Briefly, segments of the main extra-pulmonary arteries near the hilum were removed under aseptic conditions and dissected free from connective and fat tissues. The medial wall of the pulmonary artery was dissected away from the adventitia and intima and subjected to enzymatic digestion in buffer containing 1 mg/ml collagenase (Worthington Biochemical Corp., Freehold, NJ) and 0.5 mg/ml Elastase type IV (Sigma-Aldrich, St Louis, MO) for 60 min at 37 °C. A7r5, a cell line derived from rat thoracic aorta, and 293a, a cell line derived from human embryonic kidney, were purchased from American Type Culture Collection (Manassas, USA).

Tali Yaron-Eldar, an external director and the chairman of our audit committee and remuneration committee, joined our Board in March 2014. Ms. Yaron-Eldar is an Israeli attorney specializing in taxation and co-founded Yaron-Eldar, Paller, Schwartz & Co., Law Offices, in January 2013. Prior to January 2013, she was a partner at the law firm of Tadmor & Co. from March 2007 until December 2012 and a partner at the law firm of Cohen, Yaron-Eldar & Co. from 2004 until March 2007. From January 2004 until January 2008, Ms. Yaron-Eldar served as the Chief Executive Officer of Arazim Investment Company and she has also served in a variety of public positions, including as the Chief Legal Advisor of the Customs and V.A.T department of the Finance Ministry of the State of Israel from 1998 to 2001 and as the Commissioner of Income Tax and Real Property Tax Authority of the State of Israel from 2002 to 2004. Ms. Yaron-Eldar also serves as a director of a number of public companies, including Rossetta Genomics Ltd., Medtechnica Ltd., Magicjack Vocaltec Ltd., Lodgia Rotex Investments Ltd., Arko Holdings Ltd., Greenergy Renewable Energy Ltd., GO.D.M Investments Ltd., and Tadea Technological Development and Automation Ltd among others. Ms. Yaron-Eldar holds an M.B.A. specializing in finance from Tel Aviv University which was awarded in 1995 and an LL.B. from Tel Aviv University which was awarded in 1987. Ms. Yaron-Eldar is also a member of the Israeli Bar Association.

        Under the new revenue standard, we recognize revenue when our customer obtains control of promised goods or services, in an amount that reflects the consideration that we expect to receive in exchange for those goods or services. We recognize revenue following the five-step model prescribed under ASC 606: