Liquid cell transmission electron microscopy (LCTEM) is a powerful technique for investigating crystallisation dynamics with nanometre spatial resolution. However, probing phenomena occurring in liquids while mixing two precursor solutions has proven extremely challenging, requiring sophisticated liquid cell designs. Here, we demonstrate that introducing and withdrawing solvents in sequence makes it possible to maintain optimal imaging conditions while mixing liquids in a commercial liquid cell.
View Article and Find Full Text PDFsuite of internally functionalized FeL cage complexes has been synthesized with lipophilic end groups to allow dissolution in varied solvent mixtures, and the scope of their molecular recognition of a series of neutral, nonpolar guests has been analyzed. The lipophilic end groups confer cage solubility in solvents with a wide range of polarities, from hexafluoroisopropanol (HFIP) to tetrahydrofuran, and the hosts show micromolar affinities for neutral guests, despite having no flat panels enclosing the cavity. These hosts allow interrogation of the effects of an internal functional group on guest binding properties, as well as solvent-based driving forces for recognition.
View Article and Find Full Text PDFA synergistic combination of cationic styrylpyridinium dyes and water-soluble deep cavitand hosts can recognize phosphorylated peptides with both site- and state-selectivity. Two mechanisms of interaction are dominant: either the cationic dye interacts with Trp residues in the peptide or the host:dye pair forms a heteroternary complex with the peptide, driven by both strong dye-peptide and cavitand-peptide binding ( values up to 4 μM). The presence of multiple recognition mechanisms results in varying fluorescence responses dependent on the phosphorylation state and position, eliminating the need for covalent modification of the peptide target.
View Article and Find Full Text PDFProc IEEE Int Symp Biomed Imaging
May 2024
Digital Breast Tomosynthesis (DBT) is a widely used medical imaging modality for breast cancer screening and diagnosis, offering higher spatial resolution and greater detail through its 3D-like breast volume imaging capability. However, the increased data volume also introduces pronounced data imbalance challenges, where only a small fraction of the volume contains suspicious tissue. This further exacerbates the data imbalance due to the case-level distribution in real-world data and leads to learning a trivial classification model that only predicts the majority class.
View Article and Find Full Text PDFBackground: Person-centred care is becoming increasingly recognised as an important element of palliative care. The current review syntheses evidence in relation to transitions in advanced cancer patients with palliative care needs. The review focuses on specific elements which will inform the Pal-Cycles programme, for patients with advanced cancer transitioning from hospital care to community care.
View Article and Find Full Text PDFA simple aqueous host:guest sensing array can selectively discriminate between different types of citrus varietal from peel extract samples. It can also distinguish between identical citrus samples at varying stages of ripening. The discrimination effects stem from detection of changes in the terpenoid composition of the peel extracts by the host:guest array, despite the overwhelming excess of a single component, limonene, in each sample.
View Article and Find Full Text PDFSequestration of small molecule guests in the cavity of a water-soluble deep cavitand host has a variety of effects on their NMR properties. The effects of encapsulation on the longitudinal () and transverse () relaxation times of the protons in variably sized guest molecules are analyzed here, using inversion recovery and spin-echo experiments. Sequestration of neutral organic species from the bulk solvent reduces the overall proton relaxation times, but the magnitude of this effect on different protons in the same molecule has a variety of contributors, from the motion of the guest when bound, to the position of the protons in the cavity and the magnetic anisotropy induced by the aromatic walls of the host.
View Article and Find Full Text PDFIn an ongoing effort to incorporate active learning and promote higher order learning outcomes in undergraduate organic chemistry, a hybrid ("flipped") classroom structure has been used to facilitate a series of collaborative activities in the first two courses of the lower division organic chemistry sequence. An observational study of seven classes over a five-year period reveals there is a strong correlation between performance on the in-class activities and performance on the final exam across all classes; however, a significant number of students in these courses continue to struggle on both the in-class activities and final exam. The Activity Engagement Survey (AcES) was administered in the most recent course offering included in this study, and these preliminary data suggest that students who achieved lower scores on the in-class activities had lower levels of emotional and behavioral/cognitive engagement and were less likely to work in collaborative groups.
View Article and Find Full Text PDFAn indirect competitive binding mechanism can be exploited to allow a combination of cationic fluorophores and water-soluble synthetic receptors to selectively recognize and discriminate peptide strands containing a single isomeric residue in the backbone. Peptide isomerization occurs in long-lived proteins and has been linked with diseases such as Alzheimer's, cataracts and cancer, so isomers are valuable yet underexplored targets for selective recognition. Planar cationic fluorophores can selectively bind hydrophobic, Trp-containing peptide strands in solution, and when paired with receptors that provide a competitive host for the fluorophore, can form a differential sensing array that enables selective discrimination of peptide isomers.
View Article and Find Full Text PDFAdoptive transfer of ex vivo expanded tumor-infiltrating lymphocytes (TILs) have produced long-term response in metastatic cancers. TILs have traditionally been expanded from surgically resected specimens. Ultrasound-guided core needle biopsy (CNB) is an alternative method that avoids the morbidity of surgery and have added benefits which may include patients not amenable to surgery as well as the potential to produce TILs from multiple lesions in the same patient.
View Article and Find Full Text PDFSpacious M L tetrahedra can act as catalytic inhibitors for base-mediated reactions. Upon adding only 5 % of a self-assembled Fe L cage complex, the conversion of the conjugate addition between ethylcyanoacetate and β-nitrostyrene catalyzed by proton sponge can be reduced from 83 % after 75 mins at ambient temperature to <1 % under identical conditions. The mechanism of the catalytic inhibition is unusual: the octacationic Fe L cage increases the acidity of exogenous water in the acetonitrile reaction solvent by favorably binding the conjugate acid of the basic catalyst.
View Article and Find Full Text PDFFlexible, water-soluble hosts are capable of selective molecular recognition in cellular environments and can detect neurotransmitters such as choline in cells. Both cationic and anionic water-soluble self-folded deep cavitands can recognize suitable styrylpyridinium dyes in cellular interiors. The dyes selectively accumulate in nucleotide-rich regions of the cell nucleus and cytoplasm.
View Article and Find Full Text PDFWater-soluble deep cavitands with cationic functions at the lower rim can selectively bind iodide anions in purely aqueous solution. By pairing this lower rim recognition with an indicator dye that is bound in the host cavity, optical sensing of anions is possible. The selectivity for iodide is high enough that micromolar concentrations of iodide can be detected in the presence of molar chloride.
View Article and Find Full Text PDFAppending functional groups to the exterior of Zn L self-assembled cages allows gated control of anion binding. While the unfunctionalized cages contain aryl groups in the ligand that can freely rotate, attaching inert functional groups creates a "doorstop", preventing rotation and slowing the guest exchange rate, even though the interiors of the host cavities are identically structured. The effects on anion exchange are subtle and depend on multiple factors, including anion size, the nature of the leaving anion, and the electron-withdrawing ability and steric bulk of the pendant groups.
View Article and Find Full Text PDFAn arrayed host:guest fluorescence sensor system can discriminate DNA G-quadruplex structures that differ only in the presence of single oxidation or methylation modification in the guanine base. These small modifications make subtle changes to G4 folding that are often not detectable by CD but induce differential fluorescence responses in the array. The sensing is functional in diluted serum and is capable of distinguishing individual modifications in DNA mixtures, providing a powerful method of detecting folding changes caused by DNA damage.
View Article and Find Full Text PDFResearch from randomized controlled trials initiated up to 60 years ago consistently confirms that regular screening with mammography significantly reduces breast cancer mortality. Despite this success, there is ongoing debate regarding the efficacy of screening, which is confounded by technologic advances and concerns about cost, overdiagnosis, overtreatment, and equitable care of diverse patient populations. More recent screening research, designed to quell the debates, derives data from variable study designs, each with unique strengths and weaknesses.
View Article and Find Full Text PDFSelf-assembled FeL cage complexes with variable internal functions can be synthesized from a 2,7-dibromocarbazole ligand scaffold, which orients six functional groups to the cage interior. Both ethylthiomethylether and ethyldimethylamino groups can be incorporated. The cages show strong ligand-centered fluorescence emission and a broad range of guest binding properties.
View Article and Find Full Text PDFSynthetic receptors are powerful tools for molecular recognition. They can bind to guests with high selectivity and affinity, and their structures are tunable and diversified. These features, plus the relatively low cost and high simplicity in synthesis and modification, support the feasibility of array-based molecular analysis with synthetic receptors for improved selectivity in the recognition of a wide range of targets.
View Article and Find Full Text PDFSimple macrocyclic water-soluble hosts such as cucurbiturils, cyclophanes, and calixarenes have long been used for biosensing via indicator displacement assays. Using multiple hosts and dyes in an arrayed format allows pattern recognition-based "chemical nose" sensing, which confers exquisite selectivity, even rivaling the abilities of biological recognition tools such as antibodies. However, a challenge in indicator displacement-based biosensing with macrocyclic hosts is that selectivity and scope are often inversely correlated: strong selectivity for a specific target can limit wide application, and broad scope sensing can suffer from a lack of selectivity between similar targets.
View Article and Find Full Text PDFJ Breast Imaging
January 2022
Launching an academic career in breast imaging presents both challenges and opportunities for the newly graduated trainee. A strategic plan aligned with one's personal strengths and interests facilitates career success and professional satisfaction. Academic departments offer multiple tracks to accommodate diverse faculty goals.
View Article and Find Full Text PDFA self-assembled Fe L cage was synthesized with 12 internal amines in the cavity. The cage forms as the dodeca-ammonium salt, despite the cage carrying an overall 8+ charge at the metal centers, extracting protons from displaced water in the reaction. Despite this, the basicity of the internal amines is lower than their counterparts in free solution.
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