Continuous-flow experiments Researchers in China report a continuous-flow process for the preparation of m-nitrothioanisole via diazotization of m-nitroaniline to afford a diazonium chloride intermediate, which is then subjected to azo coupling with sodium thiomethoxide to give 1-(methylthio)-2-(3-nitrophenyl)diazene, followed by dediazonization to provide m-nitrothioanisole in high yield (2). A flow process was developed to minimize accumulation of the energetic intermediate diazonium salt and enable large-scale production.

           The aggregate market value of the common stock held by non-affiliates of the Registrant was approximately $226.8 million based upon the closing price of the common stock as reported on the Nasdaq Global Market on June 29, 2018, the last business day of the Registrant’s most recently completed second fiscal quarter. As of March 1, 2019, there were 42,188,517 shares of the Registrant’s common stock outstanding, $0.001 par value per share.

        The total intrinsic values of options exercised totaled $0.9 million and $1.4 million for the years ended December 31, 2018 and 2017, respectively. The intrinsic value was calculated as the difference between the fair value of the Company’s common stock and the exercise price of the option. The weighted-average grant date fair value of stock options granted was $6.63 and $11.57 for years ending December 31, 2018 and 2017, respectively.

        The terms of the Merck Agreement contain multiple promised goods and services, which include licenses, research and development activities and participation on the joint steering committee. Payments under the agreement include: (i) an upfront nonrefundable license fee; (ii) payments for research and development services performed by us, including reimbursement for certain lab supplies and reagents; (iii) payments based upon the achievement of certain development (pre-clinical and clinical), regulatory and commercial milestones; and (iv) royalties on net product sales, if any.

Derma Sciences, Inc. (NasdaqCM:DSCI) is a medical technology company focused on three segments of the wound care marketplace, traditional dressings, advanced wound care dressings and pharmaceutical wound care products. Its MEDIHONEY® product is the leading brand of honey-based dressings for the management of wounds and burns. The product has been shown to be effective in a variety of indications, and was the focus of a positive large-scale, randomized controlled trial involving 108 patients with leg ulcers. Other novel products introduced into the $14 billion global wound care market include XTRASORB® for better management of wound exudates, and BIOGUARD® for infection prevention. As noted above, Derma Sciences expects to complete the efficacy portion of its Phase 2 clinical study with DSC127, a novel pharmaceutical for accelerated wound healing and scar reduction, by the end of 2010.

The FDA’s standard is to be below an amount that would be expected (by their dose/response modeling) to cause 1 extra cancer case in 100,000 people who were taking the tablets at a standard dose for 70 straight years. That’s pretty stringent, considering the background rates of cancer in people who actually stay alive for 70 years in a row, especially when you factor in that no one goes on valsartan when they’re ten years old. Unfortunately, the ZHP material (according to the FDA) would be expected to cause one extra case of cancer with only 8,000 patients taking the highest dose of the drug for only four years, and that’s definitely unacceptable. It appears that the other manufacturers’ batches had contaminants at lower levels, from what I can see, although the amounts do not appear to have been specified.

For purposes of the shareholder vote, unless a court rules otherwise, the merger will not be deemed approved if a majority of the shares voting at the shareholders meeting (excluding abstentions) that are held by parties other than the other party to the merger, any person who holds 25% or more of the means of control of the other party to the merger or any one on their behalf including their relatives or corporations controlled by any of them, vote against the merger. In addition, if the non-surviving entity of the merger has more than one class of shares, the merger must be approved by each class of shareholders.

Hi Paul, After 6 months on Rapamycin had decrease hemoglobin, lymphocytes and polys as reported. This due to putting brake on hematopoietic stem cells. Mild anemia very common effect. I consider this benevolent side effect and helps protect stem cells from development senescent cells which much bigger problem. So slight inhibition stem cells real and probably part of anti-aging effect.

The EMA also recently issued a reflection paper to provide guidance on drug development in the field of NASH. However, the EMA indicated, among other things, that both resolution of NASH without worsening of fibrosis and improvement in fibrosis without worsening of NASH would both be required as intermediate endpoints for demonstrating statistical significance for stage 2 and 3 fibrosis.

(a) Tumor cell-induced Ca2+ signals in NK cells from TRPM2+/+ or TRPM2−/− mice. Arrow indicates the time of addition of B16F10 tumor cells. Data are mean ± SEM of three independent experiments. *P < 0.001 vs basal; #P < 0.05. (b) Impairment of degranulation in TRPM2−/− NK cells upon stimulation with B16F10 cells. TRPM2+/+ or TRPM2−/− NK cells were stimulated with target cells for 2 h at 37°C and then stained with FITC-conjugated anti-CD107a mAb and PE-conjugated anti-NK1.1 mAb. NK cells were gated on forward scatter/side scatter characteristics. (c) Reduced granzyme B release in tumor cell-stimulated TRPM2−/− NK cells. The amount of granzyme B released into the media was measured by ELISA after incubation with NK cells and B16F10 cells for 30 min. (d) Decrease in cytolytic activity against B16F10 cells in TRPM2−/− NK cells. TRPM2+/+ or TRPM2−/− NK cells were assessed for cytolytic activity against B16F10 target cells in a 4-h calcein-release assay. Data shown in b, c, and d are representative of three independent experiments. *P < 0.001. (e) B16F10 cells (1 × 105) were injected into the flanks of TRPM2+/+ and TRPM2−/− mice (n = 10 per cohort), and tumor growth was monitored. *P < 0.001. (f) Kaplan-Meier plot of TRPM2+/+ and TRPM2−/− recipient mice after s.c. injection with B16F10 cells (1 × 105) (n = 10 per cohort). (g) Antitumor effect of TRPM2+/+ or TRPM2−/− NK cells in the lung metastasis model of B16F10 cells. TRPM2−/− mice (n = 4 per cohort) were injected i.v. with 1 × 105 B16F10 melanoma cells. IL-2 activated NK cells (2 × 106 cells) from TRPM2+/+ or TRPM2−/− mice were injected i.v. into B16F10-bearing TRPM2−/− mice 2 d later. Lungs were harvested 14 d after and fixed with 4% paraformaldehyde, and metastatic nodules were counted. Representative images of lungs are shown. *P < 0.01.

Hi Heather Your IGF is probably good. Two things seem to bring it up in almost equal fashion, animal proteins and refined carbohydrates. I do eat fish and chicken but no refined carbohydrates to speak of, so maybe I should start substituting pea protein for the chicken at least. As for metformin, the more I read about it the more I like it, but I’ll start with 250mg and work my way up, while trying the b12 that you recommended. Need my insulin at 5 and IGF at 130. Keep walking fast. Highly predictive.

Given our stage of development, we do not have any internal sales, marketing or distribution infrastructure or capabilities. In the event we receive regulatory approval for Aramchol, we intend, where appropriate, to pursue commercialization relationships, including strategic alliances and licensing, with pharmaceutical companies and other strategic partners, which are equipped to market and/or sell Aramchol or any future product candidates, if any, through their well-developed sales, marketing and distribution organizations in order to gain access to global markets. In addition, we may out-license some or all of our worldwide patent rights to more than one party to achieve the fullest development, marketing and distribution of any products we develop. Over the longer term, we may consider ultimately building an internal marketing, sales and commercial infrastructure. See “Item 4. Information on the Company—Business Overview—Strategic Collaborations, Research Arrangements and other Material Agreements—Samil Pharm Co.” for information regarding the license agreement we entered with Samil for the commercialization of Aramchol (with an option to manufacture) for the treatment of fatty liver indications including NASH, in the Republic of Korea.