For information concerning our research and development policies and a description of the amount spent during each of the last three fiscal years on company-sponsored research and development activities, see “Item 5. Operating and Financial Review and Prospects—Results of Operations.”

The best example is the famous J curve for alcohol in which small amounts are beneficial at low doses for the heart and huge amounts are horrible (although a recent meta-analysis has challenged this [ Lancet vol. 392 pp. 1015 – 1035 ’18 ], but I don’t trust them — for why see http://science.sciencemag.org/content/sci/361/6408/1184.full.pdf.

Generally, under the Companies Law and the Articles, shareholder resolutions are deemed adopted if approved by the holders of a simple majority of the voting rights represented at a meeting and voting unless a different majority is required by law or pursuant to the Articles. The Companies Law provides that resolutions on certain matters, such as amending a company’s articles of association, assuming the authority of the board of directors in certain circumstances, appointing auditors, appointing external directors, approving certain transactions, increasing or decreasing the registered share capital and approving most mergers must be made by the shareholders at a general meeting. A company may determine in its articles of association certain additional matters in respect of which resolutions by the shareholders in a general meeting will be required.

Ocarino, N. M. et al. Osteogenic differentiation of mesenchymal stem cells from osteopenic rats subjected to physical activity with and without nitric oxide synthase inhibition. Nitric Oxide 19, 320–325 (2008).

We are unable to estimate our long-term capital requirements due to uncertainties associated with the development and commercialization of Aramchol. If we fail to obtain necessary funds for our operations, we will be unable to develop and commercialize Aramchol and any future product candidates.

Mannikko, R., Pandey, S., Larsson, H. P. & Elinder, F. Hysteresis in the voltage dependence of HCN channels: conversion between two modes affects pacemaker properties. J Gen Physiol 125, 305–26 (2005).

        Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated, as of the end of the period covered by this Annual Report on Form 10-K, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act). Based on that evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure controls and procedures were effective at the reasonable assurance level as of December 31, 2018

Mesenteric artery rings of blood stasis rats were isolated after oral administration with β-BA (100 mg/kg/d or 200 mg/kg/d) for 7 times. β-BA induced relaxation in aortic rings with (a) or without endothelium (b) was determined. The tension responsible for the vascular relaxation and constriction was tested. The contraction was induced by 0.5 mM phenylephrine. The results are expressed as percentage of relaxation for comparison with the remaining controlled tension (Mean ± SEM, n = 8). Experimental groups: control (■), model (⧫), model + β-BA 200 mg/kg (▲), model + β-BA 100 mg/kg (×). ##p < 0.01 versus the control group, #p < 0.05 versus the control group, **p < 0.01 versus the model group, *p < 0.05 versus the model group.

To assess whether the defect in B16F10 tumor control was due to NK cell dysfunction, we adoptively transferred IL-2 activated NK cells from TRPM2+/+ and TRPM2−/− mice into B16F10 tumor-bearing TRPM2−/− mice. Following B16F10 tumor cell injection, a markedly higher number of metastatic cells were observed in TRPM2−/− NK cell-treated mice than in TRPM2+/+ NK cell-treated mice (Fig. 1g). These findings suggest that TRPM2-deficient NK cells have an intrinsic defect in antitumor activity.

        Pursuant to the requirements of the Securities Exchange Act of 1934, this Report has been signed below by the following persons on behalf of the Registrant and in the capacities and on the dates indicated.

一系列的证据证明激素在肿瘤转移当中扮演辅助角色。一种理论认为过量的激素刺激目标器官会使其细胞分裂增多；分裂过程中偶发的基因传递差错日积月累就导致肿瘤形成。激素依赖组织相关的肿瘤占美国新诊断的肿瘤中的20%以上。治疗前列腺癌的目标就是移除雄激素的刺激，而治疗乳腺癌要降低雌激素刺激。只有肿瘤细胞含有相应的甾体激素受体时这种治疗方法才能发挥作用。

Alan Turing has, among other things contributed to formalized the concept of computability (what functions can be computed by a machine). He has discovered a model of abstract computer (called Turing’s machine) which is heavily used in theoretical computer science and complexity theory. He is also known for his work in AI and in particular for having invented the “Turing test” to decide about the intelligence of machines.