Sales of a substantial number of our ordinary shares in the public market, or the perception that these sales might occur, could depress the market price of our ordinary shares and could impair our ability to raise capital through the sale of additional equity securities. We are unable to predict the effect that sales may have on the prevailing market price of our ordinary shares. To date, the lock-up period has expired and substantially all of our outstanding shares are eligible for unrestricted sale. Sales of shares by these shareholders would likely result in the supply of our ordinary shares far exceeding the demand for our ordinary shares and could have a material adverse effect on the trading price of our ordinary shares.

In endothelial cells, NO is synthesized from substrate L-arginine via eNOS, and the phosphorylation of specific serine residue (Ser-1177) in eNOS is significant for its enzymatic activity43. Endothelium eNOS is the predominant isoform of NO synthase in vasculature and catalyzes the generation of NO44. Hallmark of a dysfunctional endothelium is an impaired action of the enzyme eNOS45. Western blot and immunofluorescence as well as immunohistochemistry revealed that β-BA could increase phosphorylation of eNOS at Ser1177 (Fig. 4). Endothelial dysfunction was mainly demonstrated by reduction of NO bioavailability46. In an isolated aortic ring, acetylcholine (ACh) induced endothelium-dependent relaxations, and the relaxations were abolished by eNOS inhibitor L-NAME47. NO formation was markedly reduced by L-NAME in blood stasis rats. β-BA treatment showed better contractile response in aorta compared with the model group, suggesting a higher NO formation in the vessel (Fig. 5a). Pretreatment with β-BA before OGD damage could significantly increase cell viability (Fig. 5b). However, the protective effect was reduced by knockdown of eNOS, which suggests eNOS is required for β-BA mediated endothelial protection.

In case of termination for reasons of disability or death, the grantee or his legal successor may exercise options that have vested prior to termination within a period of twelve months from the date of disability or death. If we terminate a grantee’s employment or service for cause, all of the grantee’s vested and unvested unexercised options will expire and terminate on the date of termination. If a grantee’s employment or service is terminated for any other reason, the grantee may exercise his or her vested options within 90 days of the date of termination or within a longer period under specified circumstances determined by our Board. Any expired or unvested options shall return to the option pool reserved under the 2013 Plan for reissuance.

There may be other reasons to prefer one or another NSAID.  There are benefits for joint pain and stiffness; there are risks for gastric pain and ulcers.  It’s an individual choice, and I encourage you to experiment on yourself.  You can alternate different NSAIDs, but it’s best to do so week-by-week or month-by-month, rather than daily.  Don’t take aspirin and other NSAIDs in the same week.

In 2016, we performed a PK study involving 66 Chinese subjects, or the Chinese PK Study, who are domiciled in the United States, consisting of two parts. Overall treatment with Aramchol 400 mg and 600 mg was well tolerated, all adverse events were mild, and no safety signal was identified. No serious adverse events or deaths were reported. We deemed no changes were required in the enrollment of Chinese patients into the ARREST Study

        For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and where the license is deemed to be the predominant item to which the royalties relate, the Company recognizes revenue at the later of: (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). To date, the Company has not recognized any royalty revenue resulting from the Merck Agreement.

Our Board has resolved to delegate to the audit committee the power to pre-approve non-auditing services rendered by the Company’s independent auditors without the need for further approval by our Board. As such, on March 10, 2019, our audit committee approved the adoption of a pre-approval policy, such that the Chairman of the audit committee is authorized to pre-approve any engagement of our independent auditors during a period of twelve months from the date of such approval, for the provision of non-auditing services, for fees not to exceed $20,000, and any such engagement which exceeds $20,000 shall require a pre-approval by the entire audit committee. Once services have been pre-approved, our management must then report to the audit committee on a periodic basis regarding the extent of services actually provided in accordance with the pre-approval policy, and regarding the fees for the services performed. Such fees for 2017 were pre-approved by the audit committee in accordance with the pre-approval policy.

        The patent positions of pharmaceutical, biotechnology and other life sciences companies can be highly uncertain and involve complex legal and factual questions for which important legal principles remain unresolved. Changes in either the patent laws or in interpretations of patent laws in the U.S. and other countries may diminish the value of our intellectual property. Further, the determination that a patent application or patent claim meets all of the requirements for patentability is a subjective determination based on the application of law and jurisprudence. The ultimate determination by the USPTO or by a court or other trier of fact in the U.S., or corresponding foreign national patent offices or courts, on whether a claim meets all requirements of patentability cannot be assured. For example, our lead C5 inhibitor portfolio consists of six families of patent applications that we own directed to our lead C5 inhibitor and related methods of use. Although we have conducted searches for third-party publications, patents and other information that may affect the patentability of claims in our various patent applications and patents, we cannot be certain that all relevant information has been identified. Accordingly, we cannot predict the breadth of claims that may be allowed or enforced in our patents or patent applications, in our licensed patents or patent applications or in third-party patents.

The Company reviews the individual securities in its portfolio to determine whether a decline in a security’s fair value below the amortized cost basis is other-than-temporary. The Company determined that as of December 31, 2018 and 2017 there were no investments in its portfolio that were other-than-temporarily impaired.

there is no need to quench azide in situ with nitrite in the reaction mix with the product – they could have done it with mother liquors after acidification and precipitating the product, it is just that the process people are paranoid about the safety and they wanted avoid any chance of hydrazoic acid vapors – literaly a headache-causing problem for the operators who have to filter the stuff on scale

NK cell degranulation was assessed as previously described41. Briefly, 2 × 105 NK cells were added to 2 × 105 target cells in 200 μl of complete medium. Cells were mixed, centrifuged for 3 min at 20 × g, and incubated for 2 h at 37°C. Thereafter, cells were centrifuged, stained with fluorochrome-conjugated mAbs against NK1.1 and CD107a (BD Biosciences) in PBS supplemented with 2% FBS and 2 mM EDTA for 45 min on ice, washed, re-suspended in PBS supplemented with 2% FBS and 2 mM EDTA, and analyzed by flow cytometry. Data were analyzed with FlowJo version10 software.

Our research and development expenses amounted to approximately $9.7 million during the year ended December 31, 2017, representing a decrease of approximately $4.6 million, or approximately 32%, compared to approximately $14.3 million for the year ended December 31, 2016. The decrease primarily resulted from a decrease in research and development subcontractor expenses in connection with the ARREST Study of approximately $2.4 million and other studies of an aggregate of approximately $1.0 million. The decrease in the research and development expenses is also as a result of a decrease in drug development related expenses of approximately $1.0 million.