Ware, J. A. & Heistad, D. D. Seminars in medicine of the Beth Israel Hospital, Boston. Platelet-endothelium interactions. N Engl J Med. 328, 628–635 (1993).

Dyax Corp (NasdaqGM: DYAX ) Dyax is focused on advancing novel biotherapeutics for unmet medical needs, with an emphasis on inflammatory and oncology indications. Dyax utilizes its proprietary drug discovery technology to identify antibody, small protein and peptide compounds for clinical development. Dyax’s lead product candidate is DX-88 (ecallantide), a recombinant small protein that is currently being evaluated for its therapeutic potential in two separate indications. On March 26, 2009, the Company received a complete response letter from the U.S. Food and Drug Administration (FDA) regarding the review of Dyax’s Biologics License Application (BLA) of DX-88 for the treatment of hereditary angioedema (HAE). The Company intends to respond to the FDA’s requests in a timely manner. DX-88 has orphan drug designation in the U.S. and E.U., as well as Fast Track designation in the U.S., for the treatment of acute attacks of HAE. Additionally, DX-88 is being evaluated in Phase 2 trials for the prevention of blood loss during on-pump cardiothoracic surgery (CTS), which are being conducted by Dyax’s partner, Cubist Pharmaceuticals. Dyax licensed to Cubist the intravenous formulation of DX-88 for surgical indications in North America and Europe. DX-88 and other compounds in Dyax’s pipeline were identified using its patented phage display technology, which rapidly selects compounds that bind with high affinity and specificity to therapeutic targets. Dyax leverages this technology broadly with over 70 revenue generating licenses and collaborations for therapeutic discovery, as well as in non-core areas such as affinity separations, diagnostic imaging, and research reagents. Dyax is headquartered in Cambridge, Massachusetts.

Ruwhof, C. & van der Laarse, A. Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc. Res. 47, 23–37 (2000).

/s/ DAVID C. LUBNER David C. Lubner Executive Vice President and Chief Financial Officer (Principal Financial and Accounting Officer)

Boswellia serrata’s gum resin is one such plant used in Indian Ayurvedic and folk medicine to treat blood disorders and curtail inflammatory diseases like rheumatoid arthritis and to promote cardiac health24,25. Present study aims to investigate the mechanism of β-BA, an active triterpenoid compound from the extract of boswellia serrate, to protect endothelial function from blood stasis. Here, β-BA’s effective protection of endothelial function against blood stasis insult is firstly explained.

In June 2016, FASB issued ASU No. 2016-13, “Financial Instruments – Credit Losses – Measurement of Credit Losses on Financial Instruments”, which introduces a model based on expected losses to estimate credit losses for most financial assets and certain other instruments. In addition, for available-for-sale debt securities with unrealized losses, the losses will be recognized as allowances rather than reductions in the amortized cost of the securities. The ASU is effective for the Company in the first quarter of 2020, with early adoption permitted. The Company is currently evaluating the effect the adoption of this ASU will have on its consolidated financial statements.

At the end of the experiments, rats’ carotid aortas were sampled and fixed in 4% phosphate buffered formaldehyde for 2 to 3 days20. After paraffin embedding tissue blocks were cut in 4 μm slices and tissue sections collected on poly-L-lysine-coated glass slides were treated by microwave for antigen unmasking. anti-eNOS (phospho Ser1177) antibody (Abcam, cambridge, UK) were used as primary antibodies at dilutions of 1:100 (eNOS) incubated overnight at 4 °C, followed by incubation with the appropriate secondary horseradish-peroxidase labeled antibodies in accordance to the instructions of the LSAB + System HRP kit (DAKO, Hamburg, Germany) and development using DAB as chromogen. The sections were examined by light microscopy (Zeiss Axioscop 40, Jena, Germany).

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

d. In addition, the product has been subject to a regulatory review period before its commercial marketing or use, and

        We do not currently own or operate manufacturing facilities for the production of clinical or commercial quantities of our product candidates. We intend to rely on third-party contract manufacturers to produce our products and have recruited personnel with experience to manage the third-party contract manufacturers producing our product candidates and other product candidates or products that we may develop in the future.

At the end of the experimental period, the carotid arteries was immediately isolated from a rat, and cut into segments of about 20 mg/tissue. The homogenate was centrifuged at 10,000 × g for 5 min, and the supernatant was removed and extracted three times with 1.5 ml of water-saturated diethyl ether. cGMP content was measured by the equilibrated radioimmunoassay as described previously51. In brief, standards or samples were introduced in a final volume of 100 μl of 50 mM sodium acetate buffer (pH 4.8). Then, 100 μl diluted cGMP antiserum and iodinated cGMP were added in succession and incubated for 24 h at 4 °C. The bound form was separated from the free form by charcoal suspension. Results were expressed as nanomole cGMP generated per milligram of protein (nmol/mg of protein).

This meta-analysis has several limitations. Most importantly, the eligible RCTs usually had small populations and short follow-up (up to 6 months in 8/9 included studies). The included studies were also heterogeneous with regards to population characteristics (there were patients with hyperlipidemia, renal failure or atrial fibrillation), study design, and statin preparation and dose. In order to cover these variabilities we used a more conservative random-effects model and performed the sensitivity analysis. The meta-regression analysis also revealed that none of the moderator parameters i.e. statin dose, duration of statin therapy and baseline ADMA concentrations were significantly associated with the pooled estimate of statin effect on plasma ADMA concentrations. Finally, the smoking status, an important determinant of ADMA levels (as well as other variables, such as: hyperhomocysteinemia, hypertension, coronary artery disease, heart failure, and administration of the following drugs: antioxidants, estrogen, vitamin A, angiotensin converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and beta-adrenoreceptor blocking drugs), could not be considered in this meta-analysis due to lack of data.