Modeling glioblastoma heterogeneity as a dynamic network of cell states

Tumor cell heterogeneity is a crucial characteristic of malignant brain tumors and underpins phenomena such as therapy resistance and tumor recurrence. Advances in single-cell analysis have enabled the delineation of distinct cellular states of brain tumor cells, but the time-dependent changes in such states remain poorly understood. Here, we construct quantitative models of the time-dependent transcriptional variation of patient-derived glioblastoma (GBM) cells. We build the models by sampling and profiling barcoded GBM cells and their progeny over the course of 3\ua0weeks and by fitting a mathematical model to estimate changes in GBM cell states and their growth rates. Our model suggests a hierarchical yet plastic organization of GBM, where the rates and patterns of cell state switching are partly patient-specific. Therapeutic interventions produce complex dynamic effects, including inhibition of specific states and altered differentiation. Our method provides a general strategy to uncover time-dependent changes in cancer cells and offers a way to evaluate and predict how therapy affects cell state composition

Прикладна механіка і основи конструювання: навчально-методичний посібник

Розроблено відповідно до навчальної програми і призначено для виконання розрахунково-графічної роботи з дисципліни «Прикладна механіка і основи конструювання» студентам напряму підготовки 6.050202 «Автоматизація та компютерно-ігрегровані технології» денної та заочної форм навчання. Посібник рекомендовано також для самостійної роботи студентів, оскільки він вміщує короткі теоретичні викладки основного матеріалу дисципліни «Прикладна механіка і основи конструювання», умови завдань, приклади їх розв’язування, необхідні довідкові дані

Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson’s disease, STEM-PD

Cell replacement therapies for Parkinson’s disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022

The HOO Complex with SO2, a Matrix Isolation Study

The complex formation between HOO and SO2 in argon matrices has been studied with FTIR spectroscopy. The complex shifts of the intramolecular fundamentals of the complex components suggest the formation of a complex, where HOO acts as a lone pair donor to the sulfur atom of SO2 while its hydrogen atom is sufficiently close to one of the oxygen atoms of SO2 to give a significant blue shift of the HOO bend. The complex is rapidly decomposed by irradiation at 266 nm. A comparison between the spectrum of the photoproduct and the spectrum of matrix isolated sulfuric acid suggests the possibility that the photoproduct is the radical formed by dissociation of one of the OH bonds of sulfuric acid

Water-olefin complexes. : A matrix isolation study

The infrared spectra of the H2O, HDO, and D2O complexes with ethylene, propene, cis-2-butene, trans-2-butene, 2-methylpropene, 2-methyl-2-butene, 2,3-dimethyl-2-butene, 1,3-butadiene, benzene, and naphthalene have been recorded at temperatures from 11 to 20 K. Interaction energies have been estimated. HDO prefers to form a deuterium bond to the unsaturated molecule; however, small amounts of the hydrogen-bonded forms are present in thermal equilibrium with the deuterium-bonded forms. The energy difference between the hydrogen-bonded and deuterium-bonded forms has been estimated for most of the complexes

The vibrational spectrum of H2O3.

This report presents positive infrared spectroscopic identification of H2O3, a higher oxide of hydrogen of importance for the understanding of the chain formation ability of atomic oxygen and a possible intermediate in hydrogen oxygen radical chemistry. All fundamental vibrations of H2O3, isolated in an argon matrix, have been observed. In addition, several bands of HDO3, D2O3, and H2(16)O2(18)O have been measured. One particular mode, the antisymetric O-O stretch at 776 cm-1, should be observable even in the presence of high water concentrations

A simple model for the water o-H-2 complex

The infrared spectrum of the complex between o-H-2 and H2O, D2O, or HDO, isolated in a matrix of solid p-H-2, has been studied between 20 and 4500 cm(-1). In addition the infrared spectrum of the complex between p-D-2 and H2O in solid o-D-2 has been studied. The spectral shifts are interpreted as the result of the quadrupole-dipole interaction between hydrogen and water. (c) 2006 American Institute of Physics

Axial motion of water hydrogen halide and water halogen complexes in argon matrices

The infrared spectra of the water (H2O, HDO, D2O) complexes with HCl, HBr, HI Cl2, Br2, and I2 have been studied in argon matrices in the 11 to 25 K interval. In all cases, water acts as a lone-pair donor. The hydrogen halide complexes are effectively planar and rotate around the axis through the heavy atoms. For the water halogen complexes, the results are less clear, but a similar rotation, coupled to low wave number bending motions, seems possible

The HOOH-HOO complex. A matrix isolation study

The peroxy radical forms a cyclic complex with hydrogen peroxide, with both entities acting as hydrogen bond donors and as hydrogen bond acceptors. The strength of the complex is very similar to that of the hydrogen peroxide dimer

Hydrogen iodide in argon matrices

The infrared spectra of HI and DI in argon matrices have been studied in the 11-25 K interval. The effects of concentration changes and of impurities have been investigated. Dimer and trimer bands have been assigned, as well as bands due to binary complexes with water, hydrogen bromide, hydrogen chloride, and atomic and molecular iodine