No abstract

The JAK family and JAK/STAT pathway The Janus family of kinases (JAK) include JAK1, JAK2, JAK3 and TYK2, and are required for the physiologic signaling of cytokines and growth factors that intrinsically lack kinase activity Comprehensive review of JAK inhibitors in myeloproliferative neoplasmsMohamad Bassam Sonbol, Belal Firwana, Ahmad Zarzour, Mohammad Morad, Vishal Rana and Ramon V. Tiu Abstract: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem-cell disorders, characterized phenotypically by the abnormal accumulation of mature-appearing myeloid cells. Polycythemia vera, essential thrombocythemia, primary myelofibrosis (also known as 'BCR-ABL1-negative' MPNs), and chronic myeloid leukemia (CML) are the primary types of MPNs. After the discovery of the BCR-ABL1 fusion protein in CML, several oncogenic tyrosine kinases have been identified in 'BCR-ABL1-negative' MPNs, most importantly, JAK2V617F mutation. The similarity in the clinical characteristics of the BCR-ABL1-negative MPN patients along with the prevalence of the Janus kinase mutation in this patient population provided a strong rationale for the development of a new class of pharmacologic inhibitors that target this pathway. The first of its class, ruxolitinib, has now been approved by the food and drug administration (FDA) for the management of patients with intermediate-to high-risk myelofibrosis. Ruxolitinib provides significant and sustained improvements in spleen related and constitutional symptoms secondary to the disease. Although noncurative, ruxolitinib represents a milestone in the treatment of myelofibrosis patients. Other types of JAK2 inhibitors are being tested in various clinical trials at this point and may provide better efficacy data and safety profile than its predecessor. In this article, we comprehensively reviewed and summarized the available preclinical and clinical trials pertaining to JAK inhibitors.

A stable capillary liquid jet formed by an electric field is an important physical phenomenon for formation of controllable small droplets, power generation and chemical reactions, printing and patterning, and chemical-biological investigations. In electrohydrodynamics, the well-known Taylor cone-jet has a stability margin within a certain range of the liquid flow rate (Q) and the applied voltage (V). Here, we introduce a simple mechanism to greatly extend the Taylor cone-jet stability margin and produce a very high throughput. For an ethanol cone-jet emitting from a simple nozzle, the stability margin is obtained within 1 kV for low flow rates, decaying with flow rate up to 2 ml/h. By installing a hemispherical cap above the nozzle, we demonstrate that the stability margin could increase to 5 kV for low flow rates, decaying to zero for a maximum flow rate of 65 ml/h. The governing borders of stability margins are discussed and obtained for three other liquids: methanol, 1-propanol and 1-butanol. For a gravity-directed nozzle, the produced cone-jet is more stable against perturbations and the axis of the spray remains in the same direction through the whole stability margin, unlike the cone-jet of conventional simple nozzles.

No abstract

The stability of convection in an anisotropic porous medium, where the solute concentration is assumed to decay via a first-order chemical reaction, is studied. This is a simplified model for the interactions between carbon dioxide and brine in underground aquifers; the instability of which is essential in reducing reservoir mixing times. The key purpose of this paper is to explore the role porous media anisotropy plays in convective instabilities. It is shown that varying the ratio of horizontal to vertical solutal diffusivites does not significantly affect the behaviour of the instability. This is also the case for changes of permeability when the diffusion rate dominates the solute reaction rate. However, interestingly, when the solute reaction rate dominates the diffusion rate a change in the permeability of the porous material does have a substantial effect on the instability of the system. The region of potential subcritical instabilities is shown to be negligible, which further supports the novel instability behaviour.