NASH is an emerging world crisis impacting an estimated 3% to 5% of the U.S. population and an estimated 2% to 4% globally, and is associated with increased risk of liver cirrhosis, liver failure, hepatocellular cancer, as well as metabolic and cardiovascular diseases. The major characteristics of NASH are elevated liver fat, inflammation, ballooning and fibrosis.

Approximately 1 × 106 cells were treated with serum-depleted medium (0.1% FBS) for 24 h to synchronize growth. Then cells were incubated in complete culture medium for another 24 h, detached by trypsinization, stored in culture medium and recovered by centrifugation. After fixation with 75% ethanol overnight at 4 °C, cells were digested with DNase-free RNase in PBS containing 5 μg/ml propidium iodide (PI) for DNA staining (30 min at 37 °C). FACS analysis was performed using a BD FACS Calibur flow cytometer equipped with CELL Quest software.

        Net cash used in operating activities was $54.9 million for the year ended December 31, 2018 compared to $46.8 million for the year ended December 31, 2017. The increase in net cash used in operations was primarily attributable to a $10.5 million increase in our net loss as a result of higher operating expenses, primarily in connection with our pre-clinical studies and clinical trials related to our lead program zilucoplan and other research and development pipeline programs; partially offset by higher non-cash expenses, including depreciation, amortization and stock-based compensation and a net increase in operating liabilities.

A foreign corporation’s PFIC status is an annual determination that is based on tests that are factual in nature, and our status for any year will depend on our income, assets, and activities for such year. Based upon our review of our financial data, we believe that we were not a PFIC for our 2018 taxable year and we expect to be a PFIC for the 2019 taxable year. Because the PFIC determination is highly fact intensive, there can be no assurance that we will be a PFIC in 2019 or for any other taxable year.

Telomere Plus from enzymedica has been subjectively good for me. Cheaper not to buy it from their website (around 20 sterling from amazon). As for scientific evidence read this paper, ‘Identification_of_Telomerase-activating_Blends_From_Naturally_Occurring_Compounds’.

        If unacceptable side effects arise in the development of our product candidates, we, the FDA or comparable foreign regulatory authorities, the Institutional Review Boards, or IRBs, or independent ethics committees at the institutions in which our studies are conducted, or the Data Safety Monitoring Board, or DSMB, could suspend or terminate our clinical trials or the FDA or comparable foreign regulatory authorities could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. In addition, these side effects may not be appropriately recognized or managed by the treating medical staff. We expect to have to train medical personnel using our product candidates to understand the side effect profiles for our clinical trials and upon any commercialization of any of our product candidates. Inadequate training in recognizing or managing the potential side effects of our product candidates could result in patient injury or death. Any of these occurrences may harm our business, financial condition and prospects significantly.

The melt behavior (Supplementary Fig. S1a) and crystal phase (Supplementary Fig. S1b) indicate that the pyrolytic carbon on PAr and PArN possess a network structure with cross-linking thus increasing the stability of the films in water (essential to biological applications). Therefore, our strategy effectively avoids alteration of the bulk properties of the implant, delamination, and release of small molecules as a result of the tertiary amines being derived from the bulk macromolecular chain. In addition, the atomic force microscopy (AFM) images (Supplementary Fig. S1c) show that the surface on PAr and PArN is rougher because Ar PIII produces cross-linked structures and during cooling, structural reorganization and contraction of the PE substrate under the pyrolytic carbon film produce interior stress between the substrate and film making the pyrolytic carbon films wrinkled.

Possibly the DOOFUS are ruling the world but I don’t have a good answer to that. I can only quote Churchill: “Democracy is the worst form of government, except for all the others”

TRPM2 is expressed in the plasma membranes as well as in intracellular compartments. The functions of intracellular TRPM2 have been studied only on insulin secretion in pancreatic β cells15 and the maturation and chemotaxis of dendritic cells16. We show that TRPM2 is an ion channel located in the cytolytic granule, and co-migrates with CD38 to the immunological synapse upon tumor stimulation (Fig. 6). Like CD38, TRPM2 appears to be essential for sustained Ca2+ signals, directed degranulation, and cytolytic activity, suggesting that CD38 is tightly coupled to TRPM2 ion channel in inducing sustained Ca2+ signals, which may be pre-requisite for the directed migration of cytolytic granules to the immunological synapses. Therefore, cytolytic granules contain all the necessary machinery for Ca2+ signaling, including Ca2+ stores and exocytosis capabilities. The lack of either CD38 or TRPM2 results in a significant increase of tumor formation and reduced survival rates. Thus, CD38 and TRPM2 cooperate to generate the sustained Ca2+ signal and directed migration of cytolytic granules to the immunological synapse in response to tumor stimulation.

        Our failure to successfully complete clinical trials of our product candidates and to demonstrate the efficacy and safety necessary to obtain regulatory approval to market any of our product candidates would significantly harm our business.

        5.     The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):

NAFLD is characterized by the accumulation of fat of 5% or greater in the liver of people who drink alcohol only in moderation, or not at all. There may be numerous causes of NAFLD, however, the disease is mostly associated with a high fat, fructose-rich diet. Although NAFLD is generally asymptomatic, it is a major risk factor for liver inflammation (NASH) and scarring (fibrosis and cirrhosis). In addition, NAFLD is also associated with metabolic syndrome and cardiovascular disease. Currently, NAFLD can only be managed through lifestyle improvements, such as weight reduction and physical activity.