Jets Downstream of Collisionless Shocks: Recent Discoveries and Challenges.

Plasma flows with enhanced dynamic pressure, known as magnetosheath jets, are often found downstream of collisionless shocks. As they propagate through the magnetosheath, they interact with the surrounding plasma, shaping its properties, and potentially becoming geoeffective upon reaching the magnetopause. In recent years (since 2016), new research has produced vital results that have significantly enhanced our understanding on many aspects of jets.

Discovery of Conformationally Constrained ALK2 Inhibitors.

Despite decades of research on new diffuse intrinsic pontine glioma (DIPG) treatments, little or no progress has been made on improving patient outcomes. In this work, we explored novel scaffold modifications of , a 3,5-diphenylpyridine ALK2 inhibitor previously reported by our group. Here we disclose the design, synthesis, and evaluation of a first-in-class set of 5- to 7-membered ether-linked and 7-membered amine-linked constrained inhibitors of ALK2.

Magnetosheath Jet Formation Influenced by Parameters in Solar Wind Structures.

Magnetosheath jets are dynamic pressure enhancements observed in the terrestrial magnetosheath. Their generation mechanisms are currently debated but the majority of jets can be linked to foreshock processes. Recent results showed that jets are less numerous when coronal mass ejections (CMEs) cross the magnetosheath and more numerous when stream interaction regions (SIRs) cross it.

Fabrication of oxygen-carrying microparticles functionalized with liver ECM-proteins to improve phenotypic three-dimensional in vitro liver assembly, function, and responses.

Oxygen and extracellular matrix (ECM)-derived biopolymers play vital roles in regulating many cellular functions in both the healthy and diseased liver. This study highlights the significance of synergistically tuning the internal microenvironment of three-dimensional (3D) cell aggregates composed of hepatocyte-like cells from the HepG2 human hepatocellular carcinoma cell line and hepatic stellate cells (HSCs) from the LX-2 cell line to enhance oxygen availability and phenotypic ECM ligand presentation for promoting the native metabolic functions of the human liver. First, fluorinated (PFC) chitosan microparticles (MPs) were generated with a microfluidic chip, then their oxygen transport properties were studied using a custom ruthenium-based oxygen sensing approach.

Magnetosheath Jet Occurrence Rate in Relation to CMEs and SIRs.

Magnetosheath jets constitute a significant coupling effect between the solar wind (SW) and the magnetosphere of the Earth. In order to investigate the effects and forecasting of these jets, we present the first-ever statistical study of the jet production during large-scale SW structures like coronal mass ejections (CMEs), stream interaction regions (SIRs) and high speed streams (HSSs). Magnetosheath data from Time History of Events and Macroscale Interactions during Substorms (THEMIS) spacecraft between January 2008 and December 2020 serve as measurement source for jet detection.

Leveraging an Open Science Drug Discovery Model to Develop CNS-Penetrant ALK2 Inhibitors for the Treatment of Diffuse Intrinsic Pontine Glioma.

There are currently no effective chemotherapeutic drugs approved for the treatment of diffuse intrinsic pontine glioma (DIPG), an aggressive pediatric cancer resident in the pons region of the brainstem. Radiation therapy is beneficial but not curative, with the condition being uniformly fatal. Analysis of the genomic landscape surrounding DIPG has revealed that activin receptor-like kinase-2 (ALK2) constitutes a potential target for therapeutic intervention given its dysregulation in the disease.

Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma.

Diffuse intrinsic pontine glioma is an aggressive pediatric cancer for which no effective chemotherapeutic drugs exist. Analysis of the genomic landscape of this disease has led to the identification of the serine/threonine kinase ALK2 as a potential target for therapeutic intervention. In this work, we adopted an open science approach to develop a series of potent type I inhibitors of ALK2 which are orally bio-available and brain-penetrant.

Turbulence-Driven Ion Beams in the Magnetospheric Kelvin-Helmholtz Instability.

The description of the local turbulent energy transfer and the high-resolution ion distributions measured by the Magnetospheric Multiscale mission together provide a formidable tool to explore the cross-scale connection between the fluid-scale energy cascade and plasma processes at subion scales. When the small-scale energy transfer is dominated by Alfvénic, correlated velocity, and magnetic field fluctuations, beams of accelerated particles are more likely observed. Here, for the first time, we report observations suggesting the nonlinear wave-particle interaction as one possible mechanism for the energy dissipation in space plasmas.

Ideation and implementation of an open science drug discovery business model - M4K Pharma.

M4K Pharma was incorporated to launch an open science drug discovery program that relies on regulatory exclusivity as its primary intellectual property and commercial asset, in lieu of patents.In many cases and in key markets, using regulatory exclusivity can provide equivalent commercial protection to patents, while also being compatible with open science. The model is proving attractive to government, foundation and individual funders, who collectively have different expectations for returns on investment compared with biotech, pharmaceutical companies, or venture capital investors.

Differentiation syndrome in acute myeloid leukemia after treatment with azacitidine.

We report a case report of hyperleukocytosis, fever, hypotension, pulmonary and pericardial effusions, and acute kidney injury during initial treatment with azacitidine in a patient with AML-MRC. Collectively, the symptomatology resembled differentiation syndrome. Azacitidine has been previously associated with fever, peripheral edema, and hyperleukocytosis, but its side effect profile has never been described as similar to differentiation syndrome.