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There are no Israeli government laws, decrees, regulations or other legislation that restrict or that affect our export or import of capital, including the availability of cash and cash equivalents for use by us and our wholly-owned subsidiaries, or the remittance of dividends, interest or other payments to non-resident holders of our securities, except for ownership by nationals of certain countries that are, or have been, declared as enemies of Israel or otherwise as set forth under “Item 10. Additional Information—E. Taxation.”

Sutendra, G. et al. A metabolic remodeling in right ventricular hypertrophy is associated with decreased angiogenesis and a transition from a compensated to a decompensated state in pulmonary hypertension. J. Mol. Med. 91, 1315–1327, 10.1007/s00109-013-1059-4 (2013).

Apoptosis was measured by Annexin V-FITC/PI kit (Partec) according to the manufacturer’s instructions. After incubation with or without 5 μM 7-xylosyl-10-deacetylpaclitaxel for 48 h, the cells were spun at 1,200 g for 5 min and the supernatant was decanted. The cell pellet was re-suspended with 100 μL of Annexin-V binding buffer and 5 μL of Annexin-V dye and left in darkness at room temperature for 15 min. Following incubation, additional 400 μL of Annexin-V binding buffer were added to each sample. Ten thousand cells were acquired and analyzed by flow cytometry and FloMax software (Partec).

Failure to build our finance infrastructure and improve our accounting systems and controls could impair our ability to comply with the financial reporting and internal control requirements for publicly traded companies.

Mr. Baharaff will also be entitled to the following equity based compensation: (i) in the event that our options are cashed-out upon a Change of Control Event, all unvested options granted to Mr. Baharaff will vest immediately prior to the consummation of the Change of Control Event; (ii) if upon a Change of Control Event (a) Mr. Baharaff’s employment as chief executive officer of the Company or the surviving entity is terminated within twelve months as of the Change of Control Event, and (b) unvested options are replaced for new options of the surviving entity as part of the Change of Control Event with a vesting schedule and terms identical to the replaced options, or the Replacement Options, then (x) all unvested Replacement Options granted to Mr. Baharaff will vest immediately prior to the termination of Mr. Baharaff’s employment, and (y) Mr. Baharaff’s Replacement Options will be exercisable until the earlier of (a) two years from termination, and (b) expiration of the Replacement Options.

        If the FDA approves a product, it may limit the approved indications for use for the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess the drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs. After approval, many types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Our executive offices are located in Tel Aviv, Israel. In addition, the majority of our officers and directors are residents of Israel. Accordingly, political, economic and military conditions in Israel may directly affect our business. Since the establishment of the State of Israel in 1948, a number of armed conflicts have taken place between Israel and its neighboring countries. Any hostilities involving Israel or the interruption or curtailment of trade between Israel and its trading partners could adversely affect our operations and results of operations. In recent years, these have included hostilities between Israel and Hezbollah in Lebanon and Hamas in the Gaza strip, both of which resulted in rockets being fired into Israel, causing casualties and disruption of economic activities. In addition, Israel faces threats from more distant neighbors, in particular, Iran.

(Pretty sure I’ve shipped software that had a bug for six years, so I sort of see how this could be, but usually it was not active, the corner case was never reached for those years. Or it was ongoing but rare and non-repeatable and fell within the failure budget for a known transient failure. What’s the pharmaceutical synthesis equivalent?)

c. the application for extension was submitted by the owner of the patent or its agent, within the 60-day period beginning on the date the product received permission for commercial marketing or use;[vi],[vii]

The activity of HCN channels have been recently shown to be regulated by membrane lipids. Voltage-dependent gating of HCN channels is allosterically regulated by phosphoinositides (particularly PIP2 but not PI), phosphatidic acid (PA), and the fatty acid arachidonic acid (AA)21,22,23,24. This regulation appears independent of the action of cAMP, since their effects are still observed in channels lacking the CNBD23,24. Cholesterol, the major sterol in all mammalian plasma membranes, has been implicated in the modulation of the function of various ion channels25. Cholesterol content in the sarcolemma of cardiac myocytes has been shown to increase when serum cholesterol levels are elevated26, increasing nearly 20% in diabetes27. A recent study has indicated that cholesterol depletion by MβCD in HEK cells and ventricular myocytes impaired rabbit HCN4 channel localization into lipid rafts and shifted V1/2 of activation to more positive potentials and increased diastolic depolarization in rabbit SAN cells28. In this study, we systematically explore the regulation of the three human cardiac HCN isoforms (HCN1, HCN2, and HCN4) by membrane cholesterol.

        As of December 31, 2018, our executive officers and directors, combined with our stockholders who owned more than 5% of our outstanding common stock and their affiliates in the aggregate, beneficially own shares representing approximately 46.9% of our common stock. As a result, if these stockholders were to choose to act together, they would be able to control all matters submitted to our stockholders for approval, as well as our management and affairs. For example, these persons, if they choose to act together, would control the election of directors and approval of any merger, consolidation or sale of all or substantially all of our assets. This concentration of ownership control may: