The terms of office and employment of directors (including an officer who is a director but is not a controlling shareholder) further require the approval of the shareholders by a simple majority in addition to the approval of the Compensation Committee and the Board, in that order, and under certain circumstances, a Special Majority; with respect to a chief executive officer or an officer who is a controlling shareholder, the approval of the shareholders must be made by the Special Majority. In addition, under certain circumstances, a company may be exempt from receiving the shareholders’ approval with respect to the Terms of Office and Employment of a non-affiliated candidate for chief executive officer.

How to cite this article: Yao, Z. et al. P311 promotes renal fibrosis via TGFβ1/Smad signaling. Sci. Rep. 5, 17032; doi: 10.1038/srep17032 (2015).

The primary endpoint of the study was the change from baseline to end of study in liver triglycerides ratio as measured by magnetic resonance spectroscopy, or MRS (Aramchol 600mg vs. placebo). Secondary endpoints, demonstrated through biopsy, included fibrosis improvement by at least one stage or more without worsening of NASH (defined by an increase of inflammation and or ballooning) and NASH resolution (defined by ballooning score 0 and inflammation score 0-1 at termination) without worsening of fibrosis. Other secondary endpoints included improvement (2 points or more) in NASH activity index, as measured by NAS or SAF, without worsening fibrosis and change in baseline to week 52/termination in ALT (U/L).

But the root causes for some quality failures can be extremely difficult to sort out. This is becoming particularly evident in the valsartan recalls, which began in July 2018 after traces of the toxic nitrosamine, N-nitrosodimethylamine (NDMA), were found in the APIs used to manufacture generic sartans, the angiotensin inhibitor blockers (ARBs) prescribed to some patients to treat high blood pressure.

If an emerging growth company that prepares its financial statements in accordance with U.S. GAAP, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. x

        Significant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and other government authorities. Sales of products will depend, in part, on the extent to which third-party payors, including government health programs in the U.S. such as Medicare and Medicaid, commercial health insurers and managed care organizations, provide coverage, and establish adequate reimbursement levels for, such products. The process for determining whether a payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved. Third-party payors are increasingly challenging the prices charged, examining the medical necessity, and reviewing the cost-effectiveness of medical products and services and imposing controls to manage costs. Third-party payors may limit coverage to specific products on an approved list, or formulary, which might not include all of the approved products for a particular indication.

© 2017 American Association for the Advancement of Science. All rights Reserved. AAAS is a partner of HINARI, AGORA, OARE, CHORUS, CLOCKSS, CrossRef and COUNTER.

To date, Genentech is the only company that launched an extended-release PLG microparticle product for the delivery of a protein. This product, Nutropin Depot, releases recombinant human growth hormone for the treatment for growth hormone deficiency in pediatric patients. This product went on the market in 1999 (11). 

Natural killer (NK) cells are large globular lymphocytes that represent our innate immune response against virally-infected or transformed cells1,2. After NK cells recognize tumor cells, NK cell receptors are activated, which likely aids the formation of an immunological synapse, towards which cytolytic granules containing perforin and granzymes, and the microtubule organizing center of NK cells are polarized3,4. After the cytolytic granules fuse with the plasma membrane through the degranulation process, the secreted perforin forms pores in the plasma membrane of the tumor cells. Serine protease granzyme B enters tumor cells through perforin and induces caspase-dependent and independent apoptotic cancer cell death5,6. Intracellular Ca2+ mobilization is required for target cell adhesion, granule polarization, and the degranulation process of NK cells, which are necessary in order to display their natural cytotoxicity7. Prior study suggests that cytotoxic lymphocyte degranulation and target cell lysis are Ca2+-dependent through STIM1/ORAI1-mediated calcium influx8. Recently, it has also been reported that exocytotic granules are themselves acidic Ca2+ stores, and a more target-specific Ca2+-mobilizing messenger, such as nicotinic acid adenine dinucleotide phosphate (NAADP), has been identified as being critical for the release of Ca2+ from exocytolytic granules via their cognate two-pore channels (TPCs), leading to cytolytic activity in cytotoxic T lymphocytes (CTLs)9. However, the precise mechanism by which Ca2+ signals interplay in cytolytic granule exocytosis and the killing of NK cells has remained unclear.

Dr. Liat Hayardeny, our Chief Scientific Officer joined the Company in September 2016 bringing more than 16 years of experience in drug development at all stages as part of Teva Pharmaceuticals’ global Research and Development Division. Prior to joining Galmed, Dr. Hayardeny served as Teva’s Senior Director and Head of Research Scientific Affairs. In that capacity, Dr. Hayardeny established the scientific positioning of Teva’s innovative compounds. Additionally, Dr. Hayardeny was responsible for Teva’s relationship with institutions of higher education; managing Teva’s global research collaborations and publications. Dr. Hayardeny holds a Ph.D. from Sackler School of Medicine and an MBA from Recanati Business School at Tel Aviv University.

Kinlay, S., Libby, P. & Ganz, P. Endothelial function and coronary artery disease. Curr Opin Lipidol. 12, 383–389 (2001).

In the following paper, it is shown that a simple genetic manipulation can make worms live 10 times longer.