Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.

Japan and Russia are keen to move ahead with their island (known as the “Northern Territories” to the Japanese and “Southern Kurils” to the Russians) dispute. At the end of WWII in 1945, the Soviet Union occupied those islands and ejected 17,000 Japanese residents. Since then, Japan has been trying to get the islands back. The most concerted attempts were made during Abe’s meeting with Putin at their bilateral meeting in St Petersburg. This time round, Abe made the same proposal for joint development of the islands while Putin promised to make it easier for Japanese to visit the islands. The islands are one of the issues that have prevented the two countries from signing a formal peace treaty after the end of WWII. While skirting around the issue of the islands’ sovereignty, the armed forces of Japan and Russia agreed to have exchanges. This may help contribute to confidence building measures in the region. They also signed 11 bilateral agreements related to trade and commerce.

This procedure is available for medicinal products that do not fall within the scope of mandatory centralized authorization. Specific procedures and timelines differ between member states, but the duration of the procedure without clock-stop time is generally 210 days and based on a risk/efficacy assessment by the competent authority of the member state concerned, followed by determination of SmPC, package leaflet and label text/layout and subsequently grant of the marketing authorization. Marketing authorizations granted on this basis are not mutually recognized by other member states, but the national marketing authorization can later be used in an MRP to obtain marketing authorizations in other member states.

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

Yes, this would seem right. Also, apparently losartan-containing medicines are now being recalled for containing NMBA (N-nitrosomethylbutylamine). I wonder if someone out there thought that switching the amine base will solve the problem, instead of thoroughly considering the overall azide quench process…

Romanenko, V. G., Rothblat, G. H. & Levitan, I. Modulation of endothelial inward-rectifier K+ current by optical isomers of cholesterol. Biophys J 83, 3211–22 (2002).

atleast supplementation with nad+ increasing compounds should not be taking at the same time as rapamycin, and i am really considering if a weekly dose of rapamycin is the best approach, i would consider longer time in between.

As Andre explains, in order to synthesize the tetrazole cycle in the valsartan molecule, Zhejiang Huahai’s improved process replaced tributyltin azide with the more toxic compound, sodium azide.  As a result, the yield of tetrazole formation was much better. However, sodium nitrite was used to destroy the excess sodium azide remaining after the synthesis step. Sodium nitrite is a well-known decontaminating agent of sodium azide in acidic conditions, Andre says. 

Directive 2003/94/EC and Volume 4 of the rules governing medicinal products govern GMP in the European community. Moreover, community law requires the clinical results in support of clinical safety and efficacy based upon clinical trials conducted in the European community to be in compliance with the requirements of Directive 2001/20/EC, which implements good clinical practice in the conduct of clinical trials on medicinal products for human use. Clinical trials conducted outside the European community and used to support applications for marketing within the EU must have been conducted in a way consistent with the principles set out in Directive 2001/20/EC. The conduct of a clinical trial in the EU requires, pursuant to Directive 2001/20/EC, authorization by the relevant national competent authority where a trial takes place, and an ethics committee to have issued a favorable opinion in relation to the arrangements for the trial. It also requires that the sponsor of the trial, or a person authorized to act on his behalf in relation to the trial, be established in the community. Directive 2001/20/EC will be replaced by Regulation (EU) No. 536/2014 on Clinical Trials in the near future. Although the Regulation entered into force on 16 June 2014, the timing of its application depends on the development of a fully functional EU clinical trials portal and database, which will be confirmed by an independent audit. The Regulation becomes applicable six months after the European Commission publishes a notice of this confirmation. The entry into application of the Regulation is currently estimated to occur in 2019. Once the new Regulation becomes applicable, clinical trials law in the EU will be further harmonized.

Gou, D. et al. miR-210 has an antiapoptotic effect in pulmonary artery smooth muscle cells during hypoxia. Am. J. Physiol. Lung Cell. Mol. Physiol. 303, L682–691 (2012).

Our pre-clinical programs may not produce product candidates that are suitable for clinical trials or that can be successfully commercialized or generate revenue through partnerships.

The following tables set forth information, as of February 28, 2019 concerning all outstanding equity awards to Office Holders as of such date.