ochre

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any cloning strategy can be employed
Darwin Assembly: fast, efficient, multi-site bespoke mutagenesis | Nucleic Acids Research | Oxford Academic
easily generated in a single working day (from plasmid miniprep to transformation)
Darwin Assembly: fast, efficient, multi-site bespoke mutagenesis | Nucleic Acids Research | Oxford Academic
Darwin Assembly is a highly efficient method for simultaneous mutagenesis of multiple sites
Darwin Assembly: fast, efficient, multi-site bespoke mutagenesis | Nucleic Acids Research | Oxford Academic
Here we show a new class of small (~10 nm), compositionally engineered UCNPs that exhibit spontaneous and indefinite blinking under continuous NIR excitation without optical modulation, specialized imaging buffers, photobleaching or statistical aging
Spontaneous and indefinite blinking in upconverting nanoparticles for ångström-precision multicolour super-resolution imaging | Nature Nanotechnology
Recent development of MINFLUX reached ångström-level precision7; however, the technique requires a complex optical setup and is not easily adaptable for simultaneous multicolour imaging
Spontaneous and indefinite blinking in upconverting nanoparticles for ångström-precision multicolour super-resolution imaging | Nature Nanotechnology
U-STORM can operate with just one near-infared laser, which works to simultaneously excite nanoparticles emitting different colors
MIT and Broad Institute researchers break diffraction barrier in super-resolution microscopy | MIT News | Massachusetts Institute of Technology
small (~10nm) core-shell particles could actually be coaxed into spontaneous blinking under continuous near-infrared excitation
MIT and Broad Institute researchers break diffraction barrier in super-resolution microscopy | MIT News | Massachusetts Institute of Technology
compositionally engineered upconverting nanoparticles (UCNPs) that blink spontaneously and indefinitely
MIT and Broad Institute researchers break diffraction barrier in super-resolution microscopy | MIT News | Massachusetts Institute of Technology
amine-to-amine crosslinker
BS3 (bis(sulfosuccinimidyl)suberate) 50 mg | Buy Online | Thermo Scientific™
magic angle spinning (MAS)
Solid-state nuclear magnetic resonance
Solid-state NMR structure
Coronavirus_envelope_protein
an integral membrane protein less than 110 amino acid residues long
Coronavirus_envelope_protein
Positive staining for L1CAM and YAP/TAZ was associated with inferior survival, and YAP/TAZ was related to final liver metastasis
Growth Pattern of Hepatic Metastasis as a Prognostic Index Reflecting Liver Metastasis-Associated Survival in Breast Cancer Liver Metastasis
independently associated with favorable progression-free and overall survival
Association between the histopathological growth patterns of liver metastases and survival after hepatic surgery in breast cancer patients | npj Breast Cancer
presence of a desmoplastic HGP in the liver metastases
Association between the histopathological growth patterns of liver metastases and survival after hepatic surgery in breast cancer patients | npj Breast Cancer
in patients with liver-only or liver-dominant metastases, surgical resection of liver metastases (LM) is associated with survival between 22 and 61 months and long-term progression-free survival (PFS)
Association between the histopathological growth patterns of liver metastases and survival after hepatic surgery in breast cancer patients | npj Breast Cancer
if an algorithm can safely handle the routine 80%, human physicians can focus on the hard 20%
Here Are 3 AI Companies Betting They Can Replace Doctors
medicine isn’t just pattern-matching
Here Are 3 AI Companies Betting They Can Replace Doctors
ContactSeek, an artificial-intelligence-driven framework that uses AlphaFold3 (AF3)-predicted contact probability5 to improve the specificity of genome editors
Precise DNA base editing using AlphaFold3-based contact modelling | Nature
by minimizing imperfections in individual predictions that arise from potentially noisy input data, the application of AI-based structure prediction at scale can unveil molecular contacts that are otherwise hard to detect.
AI identifies interactions in CRISPR complexes to improve specificity of DNA editing
subtler ‘contact probabilities’
AI identifies interactions in CRISPR complexes to improve specificity of DNA editing
make these tools distinguish target sites more selectively without compromising their activity
AI identifies interactions in CRISPR complexes to improve specificity of DNA editing
Cozens’ Darwin Assembly method41
Reversal of protein chemical aging by enzymatic deglycation | Nature Communications
Transformations were scaled to achieve an average library diversity of 5 × 10⁷ colonies per round of evolution
Reversal of protein chemical aging by enzymatic deglycation | Nature Communications
To select for variants with activity
Reversal of protein chemical aging by enzymatic deglycation | Nature Communications
CMLase, an enzyme engineered to specifically reverse CML modifications formed on protein substrates
Reversal of protein chemical aging by enzymatic deglycation | Nature Communications
generalised BOIN (gBOIN)
Everything You Need to Know About BOIN Design in Clinical Trials
Multiple Toxicity BOIN (MT-BOIN) design is an extension to the standard BOIN design that can accommodate multiple toxicity types and grades
Everything You Need to Know About BOIN Design in Clinical Trials
The FDA has recognised BOIN as a fit-for-purpose methodology under certain conditions, emphasising its reliability and applicability in Early Phase dose-finding clinical trials
Everything You Need to Know About BOIN Design in Clinical Trials
BOIN utilises a decision-making framework based on predefined toxicity probability intervals that adjust the dose based on accumulating patient response data
Everything You Need to Know About BOIN Design in Clinical Trials
specify a target toxicity rate, φ, along with two alternative toxicity rates, φ1 and φ2, that would warrant dose escalation and de-escalation respectively
Everything You Need to Know About BOIN Design in Clinical Trials
maximum tolerated dose (MTD) of a single therapeutic agent
Everything You Need to Know About BOIN Design in Clinical Trials
different cancer types are characterized by different contributions from each class
A practical guide for mutational signature analysis in hematological malignancies | Nature Communications
A defining feature of mammalian aging is the persistent accumulation of chemical damage on proteins of the extracellular matrix (ECM)
Reversal of protein chemical aging by enzymatic deglycation | Nature Communications
error-prone polymerases
Phage-assisted_continuous_evolution
lagoon contains M13 bacteriophage vectors carrying the gene of interest
Phage-assisted_continuous_evolution
Proteins with greater desired activity hence confer greater infectivity to their carrier phage
Phage-assisted_continuous_evolution
relating the desired activity of a target protein with the fitness of an infectious bacteriophage
Phage-assisted_continuous_evolution
Current computational protein design methodology is well suited for increasing stability, but the design of new function remains challenging. By contrast, experimental evolution excels at generating new function but often at the cost of reduced stability.
AI-redesigned starting points and outcomes enhance protein evolution | Nature
1-h cold shock on ice
AI-redesigned starting points and outcomes enhance protein evolution | Nature
Cysteine was excluded from design to avoid oxidation
AI-redesigned starting points and outcomes enhance protein evolution | Nature
AF2-predicted structures of each redesigned BoNT protease were used as input for ProteinMPNN
AI-redesigned starting points and outcomes enhance protein evolution | Nature
Cultures were then subjected to a 1-h cold shock on ice before induction with 1 mM IPTG (Gold Biotechnology)
AI-redesigned starting points and outcomes enhance protein evolution | Nature
redesigning BoNT proteases with ProteinMPNN to improve their stability and expression while retaining catalytic function
AI-redesigned starting points and outcomes enhance protein evolution | Nature
During protease PACE, the fitness of phage encoding an evolving protease is coupled to the activity of that protease on a target substrate
AI-redesigned starting points and outcomes enhance protein evolution | Nature
We used ProteinMPNN to redesign reprogrammed proteases after laboratory evolution to restore stability, activity and soluble expression
AI-redesigned starting points and outcomes enhance protein evolution | Nature
first evolve the enzyme for enhanced thermal stability or soluble expression, then use the stabilized protein as the starting point for evolving desired properties32,33
AI-redesigned starting points and outcomes enhance protein evolution | Nature
Phage-assisted continuous evolution (PACE) is a particularly powerful protein evolution method owing to its ability to perform dozens of generations of mutation, selection and replication every 24 h without researcher intervention2,5
AI-redesigned starting points and outcomes enhance protein evolution | Nature
AI-redesigned starting points to evolve enzymes with improved properties
AI-redesigned starting points and outcomes enhance protein evolution | Nature
redesign conferred robustness that unlocked access to otherwise inaccessible highly functional sequences
AI-redesigned starting points and outcomes enhance protein evolution | Nature