Subject to certain significant conditions and limitations, any Israeli taxes paid on or withheld from distributions from us and not refundable to a U.S. Holder may be credited against the U.S. Holder’s U.S. federal income tax liability or, alternatively, may be deducted from the U.S. Holder’s taxable income. The election to deduct, rather than credit, foreign taxes, is made on a year-by-year basis and applies to all foreign taxes paid by a U.S. Holder or withheld from a U.S. Holder that year. Dividends paid on the ordinary shares generally will constitute income from sources outside the United States and be categorized as “passive category income” or, in the case of some U.S. Holders, as “general category income” for U.S. foreign tax credit purposes. Because the rules governing foreign tax credits are complex, U.S. Holders should consult their own tax advisors regarding the availability of foreign tax credits in their particular circumstances.

The 2013 Plan is administered by our Board, which, on its own or upon the recommendation of our remuneration committee or any other similar committee of the Board, shall determine, subject to applicable law, the identity of grantees of awards and various terms of the grant. Consistent with our Compensation Policy, the 2013 Plan provides for granting options to purchase our ordinary shares pursuant to Section 102 of the Israeli Income Tax Ordinance, or the Ordinance, under the capital gains route, to directors, officers and employees who are Israeli residents holding (or have a right to hold or to purchase) less than 10% of our total share capital and do not have a right to receive 10% or more of the Company’s profits.

Secondly, one of their assumptions is that somatic degradation does happen inevitably. Note that this is not a proof but an assumption. You could argue that in the 23th. century, we’ll have the technology (think nanotechnology, nanobots, ..) to prevent that. At that time, we will be in total control of our genome stability. Just a speculation.

We will require substantial additional financing to achieve our goals, and a failure to obtain this necessary capital when needed on acceptable terms, or at all, could force us to delay, reduce or eliminate our product discovery and development programs or commercialization efforts.

        PNH.    The principal competitors for our program in PNH are eculizumab and ravulizumab-cwvz, both of which are monoclonal antibody C5 inhibitors marketed by Alexion Pharmaceuticals. In addition, we are aware that there are a number of other companies that are actively developing product candidates for the treatment of PNH. These include product candidates directed at C5 inhibition such as Coversin, a small protein inhibitor of C5 in clinical development by Akari Therapeutics; ABP 959, a biosimilar product candidate in clinical development by Amgen; tesidolumab, a monoclonal antibody inhibitor of C5 in clinical development by MorphoSys AG and Novartis Pharmaceuticals; pozelimab, a monoclonal antibody inhibitor of C5 in clinical development by Regeneron Pharmaceuticals; and RG6107, a monoclonal antibody inhibitor of C5 in clinical development by F. Hoffmann La Roche. In addition, competitors include product candidates directed at C3 inhibition, such as APL 2, currently in clinical development by Apellis Pharmaceuticals, and AMY-101, currently in clinical development by Amyndas Pharmaceuticals. Lastly, we face competition from orally available small molecule inhibitors of Factor D, such as ACH 4471, in clinical development by Achillion Pharmaceuticals, and LNP023, a Factor B inhibitor in clinical development by Novartis.

If we are treated as a PFIC for any taxable year during the holding period of a Non-Electing U.S. Holder, we will continue to be treated as a PFIC for all succeeding years during which the Non-Electing U.S. Holder is treated as a direct or indirect Non-Electing U.S. Holder even if we are not a PFIC for such years. A U.S. Holder is encouraged to consult its tax advisor with respect to any available elections that may be applicable in such a situation, including the “deemed sale” election of Code Section 1298(b)(1) (which will be taxed under the adverse tax rules described above).

As of December 31, 2018, 16.994 restricted stock units (RSUs) granted to our Office Holders as a group were outstanding. For outstanding equity-based awards granted to our Office Holders, see below under “Item 6. Directors, Senior Management and Employees—E. Share Ownership—Certain Information Concerning Equity Awards to Office Holders.”

Positively-charged surfaces on implants have a similar potential to upregulate osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) as electromagnetic therapy approved for bone regeneration. Generally, their osteogenesis functions are generally considered to stem from the charge-induced adhesion of extracellular matrix (ECM) proteins without exploring the underlying surface charge/cell signaling molecule pathways. Herein, a positively-charged surface with controllable tertiary amines is produced on a polymer implant by plasma surface modification. In addition to inhibiting the TNF-α expression, the positively-charged surface with tertiary amines exhibits excellent cytocompatibility as well as remarkably upregulated osteogenesis-related gene/protein expressions and calcification of the contacted BMSCs. Stimulated by the charged surface, these BMSCs display high iNOS expressions among the three NOS isoforms. Meanwhile, downregulation of the iNOS by L-Can or siRNA inhibit osteogenic differentiation in the BMSCs. These findings suggest that a positively-charged surface with tertiary amines induces osteogenesis of BMSCs via the surface charge/iNOS signaling pathway in addition to elevated ECM protein adhesion. Therefore, creating a positively-charged surface with tertiary amines is a promising approach to promote osseointegration with bone tissues.

        In December 2018, we completed a follow on public offering of 9,645,161 shares of common stock, including the full exercise of the underwriters’ option to purchase an additional 1,258,064 shares, at $15.50 per share and received aggregate net proceeds of $140.2 million, after deducting $9.0 million of underwriting discounts and commissions and approximately $0.3 million of offering expenses.

        In February 2011, the Company recorded goodwill of $0.2 million and intangible assets of $0.7 million upon the acquisition of Cosmix. Based on the Company’s step zero goodwill impairment test, completed as of October 31, 2018 and 2017, goodwill was not impaired.

Cynapsus Therapeutics Inc.  (OTC:CYNAF, TSX:CTH.V) is a specialty pharmaceutical company developing a convenient and easy to use sublingual (oral) thin film strip for the acute rescue of "OFF" motor symptoms of Parkinson’s disease. Cynapsus’ drug candidate, APL-130277, is an easy-to-administer, fast-acting reformulation of apomorphine, which is the only approved drug (in the United States, Europe, Japan and other countries) to rescue patients from "OFF" episodes. Cynapsus is focused on maximizing the value of APL-130277 by completing pivotal studies in advance of a New Drug Application ("NDA") expected to be submitted in 2016. Over one million people in the U.S. and an estimated 4 to 6 million people globally suffer from Parkinson’s disease. Parkinson’s disease is a chronic and progressive neurodegenerative disease that impacts motor activity, and its prevalence is increasing with the aging of the population. Based on a recent study and the results of the Company’s Global 500 Neurologists Survey, it is estimated that between 25 percent and 50 percent of patients experience "OFF" episodes in which they have impaired movement or speaking capabilities. Current medications only control the disease’s symptoms, and most drugs become less effective over time as the disease progresses.

Combining results of retrieved RCTs indicated a significant reduction in plasma ADMA concentrations following treatment with statins compared with placebo (WMD: − 0.104 μM, 95%CI: − 0.131 to − 0.077, Z = − 7.577, p < 0.0001). Forest plots detailing the meta-analysis of RCTs assessing the impact of statin therapy on plasma ADMA levels is illustrated in Fig. 2. Subgroup analysis revealed a significant impact of hydrophilic statins (rosuvastatin, pravastatin and fluvastatin; n = 403; WMD: − 0.207 μM, 95%CI: − 0.427 to + 0.013, Z = − 7.250, p < 0.0001), and a non-significant effect of hydrophobic statins (simvastatin and atorvastatin; n = 321; WMD: − 0.101 μM, 95%CI: − 0.128 to − 0.074, Z = − 1.845, p = 0.065) (Fig. 3).