A selection of pictures on the theme of 'road trip'.

Tangled Bank posted a photo:

Tangled Bank posted a photo:

Tangled Bank posted a photo:

Single-domain antibodies (sdAbs) demonstrate favorable pharmacokinetic profiles for molecular imaging applications. However, their renal excretion and retention are obstacles for applications in targeted radionuclide therapy (TRT). Methods: Using a click-chemistry–based pretargeting approach, we aimed to reduce kidney retention of a fibroblast activation protein α (FAP)–targeted sdAb, 4AH29, for ¹⁷⁷Lu-TRT. Key pretargeting parameters (sdAb-injected mass and lag time) were optimized in healthy mice and U87MG (FAP⁺) xenografts. A TRT study in a pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (PDX) model was performed as a pilot study for sdAb-based pretargeting applications. Results: Modification of 4AH29 with trans-cyclooctene (TCO) moieties did not modify the sdAb pharmacokinetic profile. A 200-µg injected mass of 4AH29-TCO and an 8-h lag time for the injection of [¹⁷⁷Lu]Lu-DOTA-PEG₇-tetrazine resulted in the highest kidney therapeutic index (2.0 ± 0.4), which was 5-fold higher than that of [¹⁷⁷Lu]Lu-DOTA-4AH29 (0.4 ± 0.1). FAP expression in the tumor microenvironment was validated in a PDAC PDX model with both immunohistochemistry and PET/CT imaging. Mice treated with the pretargeting high-activity approach (4AH29-TCO + [¹⁷⁷Lu]Lu-DOTA-PEG₇-tetrazine; 3 x 88 MBq, 1 injection per week for 3 wk) demonstrated prolonged survival compared with the vehicle control and conventionally treated ([¹⁷⁷Lu]Lu-DOTA-4AH29; 3 x 37 MBq, 1 injection per week for 3 wk) mice. Mesangial expansion was reported in 7 of 10 mice in the conventional cohort, suggesting treatment-related kidney morphologic changes, but was not observed in the pretargeting cohort. Conclusion: This study validates pretargeting to mitigate sdAbs’ kidney retention with no observation of morphologic changes on therapy regimen at early time points. Clinical translation of click-chemistry–based pre-TRT is warranted on the basis of its ability to alleviate toxicities related to biovectors’ intrinsic pharmacokinetic profiles. The absence of representative animal models with extensive stroma and high FAP expression on cancer-associated fibroblasts led to a low mean tumor-absorbed dose even with high injected activity and consequently to modest survival benefit in this PDAC PDX.

We'll have a review of Planet Coaster 2 soon, but I keep making Brendy do other tasks so he's not had enough time yet to ride the rails. That means it falls to me to at least let you know that Frontier's theme park builder is out now.

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Film Editor Frankie reviews 'One Missing Piece' at The Annex Theatre.

Following the success of the group’s South Kensington debut in 2022, The Other House Covent Garden is set to open in Q4 2025. Showcasing the brand’s ’Residents Club’ concept, blending hotel flexibility, services and amenities with apartment-style accommodation and an exclusive private members’ club, The Other House Covent Garden will open in Q4 2025, featuring a showstopping panoramic rooftop bar and terrace. Located in London’s theatre district, a stone’s throw from the iconic piazza, the Royal Opera House and many of London’s most famous landmarks, The Other House Covent Garden will comprise 146 signature bedrooms and Club Flats, featuring fully-equipped kitchenettes and living spaces, an all-day street café, The Other Kitchen, destination cocktail bar, the Owl & Monkey and its private club, accessible to members and residents, including a breathtaking rooftop bar, The Peacock Lounge. With rates starting from £350 per night for a Club Flat, The Other House will bring its unique conc...

India has become the 3rd largest smart phone market in the world, having overtaken Japan in Q1 of 2013. China and America occupy the first two positions.

Various smartphone manufacturers like Apple, HTC, LG,...

London : Verso, 2022.

London : Reaktion Books, Limited, 2023.

IEEE / Institute of Electrical and Electronics Engineers Incorporated

Boston ; Berlin : Birkhäuser, 2006

Register now: 28 February 2018
A webinar sponsored by COMSOL

Gireesan Sopanam’s histrionic skills, discovered rather fortuitously, has made him an integral part of the late Kavalam Narayana Panicker’s plays for the last 34 years.

Will Akki, who remade Vijay's Thuppakki in Hindi as Holiday: A Soldier Is Never Off Duty, thwart SRK?

Euripides, the Greek playwright, got it right centuries ago: one loyal friend, he said, is worth ten thousand relatives

Archives, Room Use Only - TK5621.M35 1917

The enzyme 4-hydroxy-tetrahydrodipicolinate synthase (DapA) is involved in the production of lysine and precursor molecules for peptidoglycan synthesis. In a multistep reaction, DapA converts pyruvate and l-aspartate-4-semialdehyde to 4-hydroxy-2,3,4,5-tetrahydrodipicolinic acid. In many organisms, lysine binds allosterically to DapA, causing negative feedback, thus making the enzyme an important regulatory component of the pathway. Here, the 2.1 Å resolution crystal structure of DapA from the thermoacidophilic methanotroph Methylacidiphilum fumariolicum SolV is reported. The enzyme crystallized as a contaminant of a protein preparation from native biomass. Genome analysis reveals that M. fumariolicum SolV utilizes the recently discovered aminotransferase pathway for lysine biosynthesis. Phylogenetic analyses of the genes involved in this pathway shed new light on the distribution of this pathway across the three domains of life.

Insights were obtained into the structure of the 4-hydroxy-tetrahydrodipicolinate synthase from the thermoacidophilic methanotroph Methylacidiphilum fumariolicum SolV and the phylogeny of the aminotransferase pathway for the biosynthesis of lysine.

Cytisine, a natural product with high affinity for clinically relevant nicotinic acetylcholine receptors (nAChRs), is used as a smoking-cessation agent. The compound displays an excellent clinical profile and hence there is an interest in derivatives that may be further improved or find use in the treatment of other conditions. Here, the binding of a cytisine derivative modified by the addition of a 3-(hydroxypropyl) moiety (ligand 4) to Aplysia californica acetylcholine-binding protein (AcAChBP), a surrogate for nAChR orthosteric binding sites, was investigated. Isothermal titration calorimetry revealed that the favorable binding of cytisine and its derivative to AcAChBP is driven by the enthalpic contribution, which dominates an unfavorable entropic component. Although ligand 4 had a less unfavorable entropic contribution compared with cytisine, the affinity for AcAChBP was significantly diminished owing to the magnitude of the reduction in the enthalpic component. The high-resolution crystal structure of the AcAChBP–4 complex indicated close similarities in the protein–ligand interactions involving the parts of 4 common to cytisine. The point of difference, the 3-(hydroxypropyl) substituent, appears to influence the conformation of the Met133 side chain and helps to form an ordered solvent structure at the edge of the orthosteric binding site.

Grey got Maps, Myke got an operating system, and they both created a journal.

The West Virginia Mesothelioma Victims Center is urging person or Navy Veteran in West Virginia with mesothelioma to call them anytime for on the spot access to some of the nation's top lawyers who get best compensation results for their clients.

Perron-Frobenius theorem and linear algebra have many virtues to extol

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A continuous process for the thermal treatment of a refinery sludge, comprising the following operations: a. drying of the refinery sludge, possibly mixed with pet-coke, at a temperature ranging from 110 to 120° C.; b. gasification of the dried sludge, at a temperature ranging from 750 to 950° C., for a time of 30 to 60 minutes, in the presence of a gas containing oxygen and water vapour, with the associated production of synthesis gas (CO+H2) and a solid residue; c. combustion of the synthesis gas at a temperature ranging from 850 to 1,200° C. and recycling of the combustion products for the drying and gasification phases; and d. inertization of the solid residue, at a temperature ranging from 1,300 to 1,500° C., by vitrification with plasma torches.

This is the Call for Votes for the 2019 RSPW (Theszie) Awards. You can vote here. The Theszies are the oldest fan awards in pro wrestling history, going back to 1990 (when Mr. Perfect quite appropriately won Best Wrestler and Junkyard Dog v. Ric Flair at Clash of the Champions XI won Worst Match). They […]

This is the Call for Votes for the 2019 RSPW (Theszie) Awards. You can vote here. The Theszies are the oldest fan awards in pro wrestling history, going back to 1990 (when Mr. Perfect quite appropriately won Best Wrestler and Junkyard Dog v. Ric Flair at Clash of the Champions XI won Worst Match). They […]

Theodore Payne offers 30-plus virtual tours of native plant landscapes.

Lipid rafts are organized plasma membrane microdomains, which provide a distinct level of regulation of cellular metabolism and response to extracellular stimuli, affecting a diverse range of physiologic and pathologic processes. This Thematic Review Series focuses on Biology of Lipid Rafts rather than on their composition or structure. The aim is to provide an overview of ideas on how lipid rafts are involved in regulation of different pathways and how they interact with other layers of metabolic regulation. Articles in the series will review the involvement of lipid rafts in regulation of hematopoiesis, production of extracellular vesicles, host interaction with infection, and the development and progression of cancer, neuroinflammation, and neurodegeneration, as well as the current outlook on therapeutic targeting of lipid rafts.