1,890 research outputs found
Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors.
The pluripotent nature of human embryonic stem cells (hESCs) makes them convenient for deriving therapeutically relevant cells. Here we show using Wnt reporter hESC lines that the cells are heterogeneous with respect to endogenous Wnt signalling activity. Moreover, the level of Wnt signalling activity in individual cells correlates with differences in clonogenic potential and lineage-specific differentiation propensity. The addition of Wnt protein or, conversely, a small-molecule Wnt inhibitor (IWP2) reduces heterogeneity, allowing stable expansion of Wnt(high) or Wnt(low) hESC populations, respectively. On differentiation, the Wnt(high) hESCs predominantly form endodermal and cardiac cells, whereas the Wnt(low) hESCs generate primarily neuroectodermal cells. Thus, heterogeneity with respect to endogenous Wnt signalling underlies much of the inefficiency in directing hESCs towards specific cell types. The relatively uniform differentiation potential of the Wnt(high) and Wnt(low) hESCs leads to faster and more efficient derivation of targeted cell types from these populations
Molecular Assembly Line for Intramolecular Electron Transferring Bimetallic Fe and Mn Cyanometallate Clusters
There has been emerging worldwide research dedicated to finding molecular complexes suitable for molecule-based high-density information storage via intramolecular electron transfer. A known cyanoferrate switchable material, Prussian Blue, has inspired research efforts of Holmes et al. to create families of heterometallic Prussian Blue derivatives that display optical and magnetic behavioral transitions with the variation of light and temperature. The task for my undergraduate research project is synthesizing massive switchable molecular clusters containing cyano-bridged Fe and Mn units. During the process, Marcus-Hush theory of electron transfer was an important consideration during the synthesis of tri- and tetranuclear complexes with varying redox potentials and ligand environments to impact the movement of electrons in the metal centers. Using a method known as “self assembly” with the building blocks of [(TpR)Fe(CN)3]- (TpR = poly (pyrazolyl)borates), Manganese cation complexes, along with the combinations of 2 different bidentate ligands and 2 choices of counteranions I have produced a closely related family of novel cyanometalate complexes. When looking for electron transfer, I found that the compounds have altogether failed according to variable temperature IR spectra collected from 77 K to 300 K. I present my observed trends and further plans and predictions of the synthetic design,; this includes tuning the electron density of the metal centers and how to encourage electron transfer using electrophiles bonded to the cyanides within the structure to forcefully pull the electrons through the cyanide bridges. Ultimately, my studies have shown each unique complex helps us understand the variety of factors and challenges that relate to structure-property relationships in the manufacture of electron transfer and spin crossover complexes
Correlation of Spectral & Redox Properties of Some Ni(II) Complexes of Thiomalic Acid & Thiovanol
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Anisotropic magnetic and superconducting properties of pure and Co-doped CaFeAs single crystals
We report anisotropic dc magnetic susceptibility , electrical
resistivity , and heat capacity measurements on the single
crystals of CaFeCoAs for = 0 and 0.06. Large sized single
crystals were grown by the high temperature solution method with Sn as the
solvent. For the pure compound with = 0, a high temperature transition at
170 K is observed which is attributed to a combined spin density wave (SDW)
ordering and a structural phase transition. On the other hand, for the Co-doped
samples for = 0.06, the SDW transition is suppressed while
superconductivity is observed at 17 K. The superconducting transition
has been confirmed from the magnetization and electrical resistivity studies.
The Fe M\"ossbauer spectrum in CaFeAs indicates that the SDW
ordering is incommensurate. In the Co-doped sample, a prominent paramagnetic
line at 4.2 K is observed indicating a weakening of the SDW state.Comment: 4 pages 5 figures. Submitted to Phys. Rev.
Case 2 : Saving the Rural Ontario Maternity Services – Can We Do It?
Inaya, manager of the ‘low-risk’ project at Provincial Council for Maternal and Child Health (PCMCH), had to come up with an integrative solution for the issues encompassing maternity care in Ontario. The low-risk project aims “to design and develop effective low risk maternal and newborn strategy for Ontario (2015-2018) to ensure that all women have an equitable choice of delivery options, and access to the right level of care at the right time, no matter where they live in the province”. In response to external and internal challenges facing Ontario’s hospitals, the province has seen the closure of rural maternity programs over the last few years. The women in communities that are unable to sustain local services must travel to access distant services, and depending on the distance to the nearest referral center, may be away from their homes and communities during the critical pregnancy period and child birth. The separation of pregnant women from their families and communities can cause negative outcomes. The health and economic impacts of the inability to access local maternal programs are well documented. Different stakeholders have indicated the importance of alternative, sustainable models of interprofessional collaboration of midwifery, primary and specialty care, and the efficient allocation of human health resources (PCMCH, 2015). To create the framework of the model, PCMCH formed a leadership team and expert panel consisting of different care providers. Inaya had to identify barriers and potential solutions by engaging different care providers and exploring the challenges from their perspectives. The findings would be used to work with relevant partners, such as associations of different health care professionals, to develop potential solutions for the Ministry.
The goal of the case is to provide readers with the opportunity to apply the concept of collaboration and also explore the barriers to achieving inter-professional collaboration from the key stakeholders’ perspectives
Curiosity in exploring chemical spaces: Intrinsic rewards for deep molecular reinforcement learning
Computer-aided design of molecules has the potential to disrupt the field of drug and material discovery. Machine learning, and deep learning, in particular, have been topics where the field has been developing at a rapid pace. Reinforcement learning is a particularly promising approach since it allows for molecular design without prior knowledge. However, the search space is vast and efficient exploration is desirable when using reinforcement learning agents. In this study, we propose an algorithm to aid efficient exploration. The algorithm is inspired by a concept known in the literature as curiosity. We show on three benchmarks that a curious agent finds better performing molecules. This indicates an exciting new research direction for reinforcement learning agents that can explore the chemical space out of their own motivation. This has the potential to eventually lead to unexpected new molecules that no human has thought about so far
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