When uncertain tax positions exist, the Company recognizes the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances. The Company’s practice is to recognize interest and/or penalties related to uncertain tax positions in income tax expense.

I missed this article when it came out almost a year ago.  The “Yamanaka factors” (abbreviated OSKM) are four chemicals which, when applied together, can turn an ordinary differentiated cell (a skin cell, for example) back into the stem cell from which it came.  Pluripotent stem cells replenish all the cell needs in the body.  The offspring of a stem cell can be any kind of cell, hence “pluripotent”.  Up until ten years ago, it was thought that this was a one-way street, and that the process of differentiation was irreversible.  Then the Kyoto laboratory of Shinya Yamanaka reported success in “de-differentiating” cells by adding just four chemicals, initials O, S, K and M.  In other words, these four chemicals turn a regular skin or muscle or organ cell back into the stem cell from whence it came.

Our Board has determined that Ms. Yaron-Eldar qualifies as an audit committee financial expert pursuant to the applicable SEC rules and that Ms. Yaron-Eldar is “independent” in accordance with the Nasdaq Capital Market corporate governance requirements. For information relating to Ms. Yaron-Eldar qualifications and experience, see “Item 6. Directors, Senior Management and Employees—A. Directors and Senior Management.”

and development services provided by us and includes milestone payments that could total up to $65.0 million ($6.0 million of which have been received to date).

My guess (based on disagreement among experts) is that there are individuals for whom a great deal of high intensity exercise is beneficial, and there are others who damage their cardiovascular systems by pushing too far.  Doctors may be able to tell you if you have a heart condition that makes exercise hazardous.  My hope (based on personal experience with yoga) is that we might develop a sensitivity to our bodies, so that we can distinguish the pain of damage from the pain and resistance that always accompanies a strenuous workout.

        We are a clinical-stage biopharmaceutical company using our proprietary peptide chemistry platform to develop novel therapeutics for the treatment of serious diseases that are caused by excessive or uncontrolled activation of the complement system, a critical component of the immune system. Inappropriate activation of the complement system can quickly turn it from a beneficial defense system to an aggressor that plays a major role in immune and inflammatory diseases. The complement system, which consists of approximately 30 interacting proteins, offers a target-rich opportunity for us to leverage our proprietary peptide chemistry platform, which was pioneered by Nobel Laureate Dr. Jack Szostak, and allows us to inhibit certain uncontrolled complement pathway factors involved in complement-mediated diseases. Known as our Extreme Diversity platform, this proprietary macrocyclic peptide chemistry technology allows us to produce synthetic macrocyclic peptides that combine the diversity and specificity of antibodies with the pharmacological properties of small molecules. We believe this technology will allow us to pursue challenging targets for which only monoclonal antibodies have been developed.

BioMarin Pharmaceutical Inc. (NasdaqGS: BMRN ) BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company’s product portfolio comprises three approved products and multiple clinical and preclinical product candidates. Approved products include Naglazyme® (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin; Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; and Kuvan® (sapropterin dihydrochloride) Tablets, a product for the treatment of phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany. Other product candidates include 6R-BH4 for cardiovascular indications, which is currently in Phase 2 clinical development for the treatment of peripheral arterial disease and sickle cell disease, and PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase), which is currently in Phase 1 clinical development for the treatment of PKU.

“Doesn’t the FDA have to approve all changes to manufacturing before the product can be sold?” – I don’t know the current regs, but back in the late 1980s, the FDA approved a change in Showa Denko’s synthesis and purification of L-tryptophan (sold as a nutriceutical) without a lot of investigation or testing. S-D had a long successful history making and selling T, so the FDA took their word for it.

        Stock options granted to employees and directors under the Company’s equity plans generally have a ten-year term and vest over a period of four years, provided the individual continues to serve at the Company through the vesting dates. Options granted under all equity plans are exercisable at a price per share not less than the fair market value of the underlying common stock on the date of grant and not less than 110% of the fair market value for participants who own more than 10% of the Company’s voting power.

Pulmonary arterial hypertension (PAH) is a progressive and often life-threatening disease characterized by elevation of pulmonary arterial pressure and pulmonary vascular resistance and vascular remodeling involving the dysregulation of various components of the vessel wall1,2,3. The smooth muscle layer of the vessel wall plays a prominent role in the pathogenesis of PAH with extension of smooth muscle into smaller, non-muscular pulmonary arteries within the respiratory acinus, a common feature of all forms of PAH-associated remodeling1. Pulmonary arterial smooth muscle cells (PASMC) proliferate and migrate with medial wall thickening, resulting in decreased luminal diameter and ultimately obstruction of resistance pulmonary arteries1,4. Chronic hypoxia is a well-known stimulus for abnormal proliferation and migration of vascular smooth muscle cells and vascular remodeling in patients with PAH5,6,7. Although the cellular and molecular mechanisms involved in these proliferative and migratory responses are still not completely understood, there is very strong evidence that hypoxia-inducible transcription factors (HIF) are critically involved8,9.

激素治疗市场以9.8%的复合增速自2004年的63亿美元成长为2008年的91亿美元。 增长主要来自于主导产品Casodex, Zoladex, Aromasin, Femara 和 Arimidex的销售增长。

Hua, Y., Zhang, Y. & Ren, J. IGF-1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction: role of microRNA-1 and microRNA-133a. J. Cell. Mol. Med. 16, 83–95, 10.1111/j.1582-4934.2011.01307.x (2012).