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        Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the FCPA presents particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.

As noted above, we do not anticipate paying any cash dividends in the foreseeable future. If we were to pay dividends, we expect to pay such dividends in NIS. A dividend paid in NIS, including the amount of any Israeli taxes withheld, will be includible in a U.S. Holder’s income at a U.S. dollar amount calculated by reference to the exchange rate in effect on the date such dividend is received, regardless of whether the payment is in fact converted into U.S. dollars. If the dividend is converted to U.S. dollars on the date of receipt, a U.S. Holder generally will not recognize a foreign currency gain or loss. However, if the U.S. Holder converts the NIS into U.S. dollars on a later date, the U.S. Holder must include, in computing its income, any gain or loss resulting from any exchange rate fluctuations. The gain or loss will be equal to the difference between (i) the U.S. dollar value of the amount included in income when the dividend was received and (ii) the amount received on the conversion of the NIS into U.S. dollars. Such gain or loss generally will be ordinary income or loss and will be U.S. source income or loss for U.S. foreign tax credit purposes. U.S. Holders should consult their own tax advisors regarding the tax consequences to them if we pay dividends in NIS or any other non-U.S. currency.

EpiCept Corporation (NasdaqCM:EPCT) is focused on the development and commercialization of pharmaceutical products for the treatment of cancer and pain. The Company’s lead product is Ceplene®, which has been granted full marketing authorization by the European Commission for the remission maintenance and prevention of relapse in adult patients with Acute Myeloid Leukemia (AML) in first remission. The Company has two oncology drug candidates currently in clinical development that were discovered using in-house technology and have been shown to act as vascular disruption agents in a variety of solid tumors. The Company’s pain portfolio includes EpiCept™ NP-1, a prescription topical analgesic cream in late-stage clinical development designed to provide effective long-term relief of pain associated with peripheral neuropathies.

We consent to the incorporation by reference in Registration Statements No. 333-214244, No. 333-217898 and No. 333-224791 on Form S-8 and No. 333-221266 on Form S-3 of our report dated March 7, 2019, relating to the financial statements of Ra Pharmaceuticals, Inc. appearing in this Annual Report on Form 10-K of Ra Pharmaceuticals, Inc. for the year ended December 31, 2018.

To evaluate the possibility that TRPM2-mediated Ca2+ signaling is required for the antitumor effector function of NK cells, we first examined the tumor-induced Ca2+ change in NK cells from TRPM2+/+ and TRPM2−/− mice. We noticed robust Ca2+ signals in both TRPM2+/+ and TRPM2−/− NK cells upon contact with B16F10 cells, a melanoma tumor cell line. However, TRPM2+/+ NK cells were distinct from TRPM2−/− NK cells in their ability to sustain the Ca2+ signals. TRPM2+/+ NK cells exhibited a rapid initial increase, after which the elevated levels remained for the duration of our measurement (500 s). In contrast, TRPM2−/− NK cells were not able to sustain the initial intracellular [Ca2+] ([Ca2+]i) rise (Fig. 1a; 31.5% of area under curve (AUC) of Ca2+ trace in TRPM2+/+ NK cells). As [Ca2+]i increase is important to the degranulation of NK cells7, we investigated whether TRPM2 was involved in degranulation activity. We compared the surface expression of CD107a in TRPM2+/+ and TRPM2−/− NK cells following stimulation with B16F10. B16F10-induced degranulation was absent in TRPM2−/− NK cells (Fig. 1b). Tumor cell-induced granzyme B secretion and cytotoxicity were also completely absent in TRPM2−/− NK cells (Fig. 1c and d). We further evaluated the ability of TRPM2 to protect against B16F10 tumor growth in vivo. Consistent with our finding that TRPM2−/− NK cells have decreased cytolytic activity (Fig. 1d), we observed a defect in the ability of TRPM2 deficient mice to control B16F10 tumor formation and their consequent survival rates (Fig. 1e and f). These results suggest that TRPM2 channel-mediated Ca2+ signals are critical for the antitumor effect of NK cells.

After additional ARB products were identified as containing NDMA and NDEA impurities, the agency placed a ZHP facility on import alert and issued a warning letter to the company. Recalls of ARB medicines that might pose a risk have also been issued, and a recall list on FDA’s website is being continually updated. The agency also plans to incorporate their findings into future impurities policy development.

        Our commercial success will depend in part on obtaining and maintaining patent protection and trade secret protection for the use, formulation and structure of our products and product candidates, the methods used to manufacture them, the related therapeutic targets and associated methods of treatment as well as on successfully defending these patents against potential third-party challenges.

This is Michael Fossel you are talking about Alan, Telocyte is not a con. He has intentionally selected a trial on full blown, not early onset, Alzheimer’s to blow the whole FDA stance on aging wide open. Plus Alzheimer’s is basically the most horrible disease of aging. His approach is diametrically opposite to yours Alan because he is trying to restore gene expression to youthful levels, which entails some speeding things up, notably the metabolic digestion of aggregate proteins by glial cells, which is where his confidence comes from that this will work. He is aiming to start trials next year, but this is dependent on the FDA accepting some of Blasco’s mouse work.