The race to develop quantum computers has really heated up over the past few years. State-of-the-art systems can now run simple algorithms using dozens of qubits—or quantum bits—which are the building blocks of quantum computers.
CATL’s CIIC chassis has 1,000 km range and 10.5 kWh/100km energy consumption. To start manufacturing in Q3 2024.
Occam’s razor—the principle that when faced with competing explanations, we should choose the simplest that fits the facts—is not just a tool of science. Occam’s razor is science, insists a renowned molecular geneticist from the University of Surrey.
In a paper published in the Annals of the New York Academy of Sciences, Professor Johnjoe McFadden argues Occam’s razor—attributed to the Surrey-born Franciscan friar William of Occam (1285–1347)—is the only feature that differentiates science from superstition, pseudoscience or fake news.
Professor McFadden said, “What is science? The rise of issues such as vaccine hesitancy, climate skepticism, alternative medicine, and mysticism reveals significant levels of distrust or misunderstanding of science among the general public. The ongoing COVID inquiry also highlights how scientific ignorance extends into the heart of government. Part of the problem is that most people, even most scientists, have no clear idea of what science is actually about.”
New research suggests that if tiny primordial black holes created during the Big Bang exist, some of them may have been snared by stars and are now forced to eat their way out.
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Quantum hypothesis testing—the task of distinguishing quantum states—enjoys surprisingly deep connections with the theory of entanglement. Recent findings have reopened the biggest questions in hypothesis testing and reversible entanglement manipulation.
A microbial sensor that helps identify and fight bacterial infections also plays a key role in the development of blood stem cells, providing a valuable new insight in the effort to create patient-derived blood stem cells that could eliminate the need for bone marrow transplants.
The discovery by a research team led by Raquel Espin Palazon, an assistant professor of genetics, development and cell biology at Iowa State University, is published in Nature Communications. It builds on prior work by Espin Palazon showing that the inflammatory signals that prompt a body’s immune response have an entirely different role in the earliest stages of life, as vascular systems and blood are forming in embryos.
Espin Palazon said knowing that embryos activate the microbial sensor, a protein known as Nod1, to force vascular endothelial cells to become blood stem cells could help develop a method to make blood stem cells in a lab from a patient’s own blood.
Researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME), Argonne National Laboratory, and the University of Modena and Reggio Emilia have developed a new computational tool to describe how the atoms within quantum materials behave when they absorb and emit light.
The tool will be released as part of the open-source software package WEST, developed within the Midwest Integrated Center for Computational Materials (MICCoM) by a team led by Prof. Marco Govoni, and it helps scientists better understand and engineer new materials for quantum technologies.
“What we’ve done is broaden the ability of scientists to study these materials for quantum technologies,” said Giulia Galli, Liew Family Professor of Molecular Engineering and senior author of the paper, published in Journal of Chemical Theory and Computation. “We can now study systems and properties that were really not accessible, on a large scale, in the past.”
Targeted protein degradation (TPD) is an emerging therapeutic modality and has attracted great attention from academia and industry1,2. The prototypical TPD agents, molecular glues (MGs) and proteolysis targeting chimeras (PROTACs), can lead to temporal proteasomal degradation of the protein-of-interest (POI). PROTACs are small heterobifunctional molecules integrating an E3-ligase binder and a POI binding moiety through a synthetic linker construct. The PROTACs technology has been applied to degrade numerous pathological proteins and a rich pipeline is currently progressing into preclinical and early clinical trials3,4,5. However, overcoming PK/PD issues towards clinical compounds is demanding due to the intrinsically high molecular weight and related physicochemical properties6. On the other hand, MGs are small molecules with beneficial ‘drug-like’ physicochemical properties binding to an E3 ligase, and, similarly to PROTACs, leading to neosubstrate proteasomal degradation. Their mechanism of action is however less predictable; their often hydrophobic surface-exposed portions of the MGs seem to change the hydrophobic surface area of the E3 ligase and thereby leading to neosubstrate ubiquitination and degradation7,8. MGs have already proven their validity as marketed drugs, as there are several approved drugs or clinical compounds working by an MG mechanism (Fig. 1A), for example, the IKZF1/3 degrader thalidomide and its analogs pomalidomide and lenalidomide8, and the RBM39 degrader indisulam9. Thalidomide analogs induce selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase10. Additionally, CSNK1A1 (CK1α) was recently discovered as a lenalidomide-specific neo-substrate11. Interestingly, modification of pomalidomide or lenalidomide can have a profound impact on the degradation potency and degradation profiles. For example, CC-220 (Fig. 1A) showed 10-fold more potency in the cells than lenalidomide, and CC-885 (Fig. 1A) was found to induce degradation of the substrate GSPT112,13. Both MGs and PROTACs are emerging drug modalities providing interesting features over classical pharmacology-driven drugs by their ability to drive the destruction of proteins that have multiple functions, thereby potentially overcoming resistance mechanisms and providing new pharmacology. While PROTACs can be developed highly rationally, MGs are discovered rather serendipitously requiring synthesis and testing of large series of compounds14,15. Additionally, the discovery of MGs and PROTACs is done in a sequential, often mmol scale synthesis which is time-consuming and expensive.
In this work, to address current shortcomings in MGs discovery, we use the direct-to-biology (D2B) approach and combined the automated, high throughput miniaturized synthesis with cell-based phenotypic screening (Fig. 1B). The I.DOT (Immediate Drop on Demand Technology, a pressure-based nano dispensing technology) is employed to accelerate the synthesis of diverse MGs libraries on nano scale16,17,18,19,20,21. In a subsequent cell-based phenotypic screening cascade, the compounds are tested in the thalidomide and analog sensitive MM.1S multiple myeloma cell line which reportedly is used for MGs screening22. In this D2B screening platform, the crude compounds are directly screened on cells without further chromatographic purification or clean up. Then, the 19 best compounds are selected for re-synthesis on mmol scale followed by purification and fully characterized.
