Harnessing Cytosine for Tunable Nanoparticle Self-Assembly Behavior Using Orthogonal Stimuli.

Nucleobases control the assembly of DNA, RNA, etc. due to hydrogen bond complementarity. By combining these unique molecules with state-of-the-art synthetic polymers, it is possible to form nanoparticles whose self-assembly behavior could be altered under orthogonal stimuli (pH and temperature).

Kinetically Controlled and Nonequilibrium Assembly of Block Copolymers in Solution.

Covalent polymers are versatile macromolecules that have found widespread use in society. Contemporary methods of polymerization have made it possible to construct sequence polymers, including block copolymers, with high precision. Such copolymers assemble in solution when the blocks have differing solubilities.

Controlled node growth on the surface of polymersomes.

Incorporating nucleobases into synthetic polymers has proven to be a versatile method for controlling self-assembly. The formation of strong directional hydrogen bonds between complementary nucleobases provides a driving force that permits access to complex particle morphologies. Here, nucleobase pairing was used to direct the formation and lengthening of nodes on the outer surface of vesicles formed from polymers (polymersomes) functionalised with adenine in their membrane-forming domains.

Triggered Polymersome Fusion.

The contents of biological cells are retained within compartments formed of phospholipid membranes. The movement of material within and between cells is often mediated by the fusion of phospholipid membranes, which allows mixing of contents or excretion of material into the surrounding environment. Biological membrane fusion is a highly regulated process that is catalyzed by proteins and often triggered by cellular signaling.

Transamidation-Driven Molecular Pumps.

We report a new class of synthetic molecular pumps that use a stepwise information ratchet mechanism to achieve the kinetic gating required to sequester their macrocyclic substrates from bulk solution. Threading occurs as a result of active template reactions between the pump terminus amine and an acyl electrophile, whereby the bond-forming reaction is accelerated through the cavity of a crown ether. Carboxylation of the resulting amide results in displacement of the ring to the collection region of the thread.

Knotting matters: orderly molecular entanglements.

Entangling strands in a well-ordered manner can produce useful effects, from shoelaces and fishing nets to brown paper packages tied up with strings. At the nanoscale, non-crystalline polymer chains of sufficient length and flexibility randomly form tangled mixtures containing open knots of different sizes, shapes and complexity. However, discrete molecular knots of precise topology can also be obtained by controlling the number, sequence and stereochemistry of strand crossings: orderly molecular entanglements.

A Comparison of Global Brain Volumetrics Obtained from CT versus MRI Using 2 Publicly Available Software Packages.

Background And Purpose: Brain volumetrics have historically been obtained from MR imaging data. However, advances in CT, along with refined publicly available software packages, may support tissue-level segmentations of clinical CT images. Here, brain volumetrics obtained by applying two publicly available software packages to paired CT-MR data are compared.

Genomic Screening for Pathogenic Transthyretin Variants Finds Evidence of Underdiagnosed Amyloid Cardiomyopathy From Health Records.

Background: New treatments for transthyretin amyloidosis improve survival, but diagnosis remains challenging. Pathogenic or likely pathogenic (P/LP) variants in the transthyretin () gene are one cause of transthyretin amyloidosis, and genomic screening has been proposed to identify at-risk individuals. However, data on disease features and penetrance are lacking to inform the utility of such population-based genomic screening for

Objectives: This study characterized the prevalence of P/LP variants in identified through exome sequencing and the burden of associated disease from electronic health records for individuals with these variants from a large (N = 134,753), primarily European-ancestry cohort.

3D-Encoded DENSE MRI with Zonal Excitation for Quantifying Biventricular Myocardial Strain During a Breath-Hold.

Purpose: Right ventricular (RV) function is increasingly recognized for its prognostic value in many disease states. As with the left ventricle (LV), strain-based measurements may have better prognostic value than typical chamber volumes or ejection fraction. Complete functional characterization of the RV requires high-resolution, 3D displacement tracking methods, which have been prohibitively challenging to implement.

A catalysis-driven artificial molecular pump.

All biological pumps are autonomous catalysts; they maintain the out-of-equilibrium conditions of the cell by harnessing the energy released from their catalytic decomposition of a chemical fuel. A number of artificial molecular pumps have been reported to date, but they are all either fuelled by light or require repetitive sequential additions of reagents or varying of an electric potential during each cycle to operate. Here we describe an autonomous chemically fuelled information ratchet that in the presence of fuel continuously pumps crown ether macrocycles from bulk solution onto a molecular axle without the need for further intervention.

Head CT: Toward Making Full Use of the Information the X-Rays Give.

Although clinical head CT images are typically interpreted qualitatively, automated methods applied to routine clinical head CTs enable quantitative assessment of brain volume, brain parenchymal fraction, brain radiodensity, and brain radiomass. These metrics gain clinical meaning when viewed relative to a reference database and expressed as quantile regression values. Quantitative imaging data can aid in objective reporting and in the identification of outliers, with possible diagnostic implications.

How do we educate medical students interprofessionally about patient safety? A scoping review.

Medical education has an important role in developing attitudes, behaviors and cultures that support safe care. Increasingly, however, research has argued for a more interprofessional approach to be taken. This scoping review examines the design and impact of interprofessional education interventions involving medical students that focus on patient safety.

The effects of the skull on CT imaging of the brain: a skull and brain phantom study.

Objective: To investigate the effects of beam hardening by the skull on the measured radiodensity of the brain. To test a hypothesis that these effects of beam hardening are decreased using a monochromatic energy source.

Methods: Selected clinical cases were reviewed in illustration.

A molecular endless (7) knot.

Current strategies for the synthesis of molecular knots focus on twisting, folding and/or threading molecular building blocks. Here we report that Zn(II) or Fe(II) ions can be used to weave ligand strands to form a woven 3 × 3 molecular grid. We found that the process requires tetrafluoroborate anions to template the assembly of the interwoven grid by binding within the square cavities formed between the metal-coordinated criss-crossed ligands.

Pediatric Head CT: Automated Quantitative Analysis with Quantile Regression.

Background And Purpose: Together with quantile regression methods, such a model would have the potential for clinical utility through automated quantitative comparison of individual cases relative to their age and gender-matched peer group. Our aim was to demonstrate the automated processing of digital clinical head CT data in the development of a clinically useful model of age-related changes of the brain in the first 2 decades of life.

Materials And Methods: A total of 415 (209 female) consecutive, clinical head CTs with radiographically normal findings from patients from birth through 20 years of age were retrospectively selected and subjected to automated segmentation.

Single-Step Enantioselective Synthesis of Mechanically Planar Chiral [2]Rotaxanes Using a Chiral Leaving Group Strategy.

We report a one-step enantioselective synthesis of mechanically planar chiral [2]rotaxanes. Previous studies of such molecules have generally involved the separation of enantiomers from racemic mixtures or the preparation and separation of diastereomeric intermediates followed by post-assembly modification to remove other sources of chirality. Here, we demonstrate a simple asymmetric metal-free active template rotaxane synthesis using a primary amine, an activated ester with a chiral leaving group, and an achiral crown ether lacking rotational symmetry.

Aging and the Brain: A Quantitative Study of Clinical CT Images.

Background And Purpose: Though CT is a highly calibrated imaging modality, head CT is typically interpreted qualitatively. Our aim was to initiate the establishment of a reference quantitative database for clinical head CT.

Materials And Methods: An automated segmentation algorithm was developed and applied to 354 clinical head CT scans with radiographically normal findings (ages, 18-101 years; 203 women) to measure brain volume, brain parenchymal fraction, brain radiodensity, and brain parenchymal radiomass.

Weak functional group interactions revealed through metal-free active template rotaxane synthesis.

Modest functional group interactions can play important roles in molecular recognition, catalysis and self-assembly. However, weakly associated binding motifs are often difficult to characterize. Here, we report on the metal-free active template synthesis of [2]rotaxanes in one step, up to 95% yield and >100:1 rotaxane:axle selectivity, from primary amines, crown ethers and a range of C=O, C=S, S(=O) and P=O electrophiles.

Automated Estimation of Acute Infarct Volume from Noncontrast Head CT Using Image Intensity Inhomogeneity Correction.

Identification of early ischemic changes (EIC) on noncontrast head CT scans performed within the first few hours of stroke onset may have important implications for subsequent treatment, though early stroke is poorly delimited on these studies. Lack of sharp lesion boundary delineation in early infarcts precludes manual volume measures, as well as measures using edge-detection or region-filling algorithms. We wished to test a hypothesis that image intensity inhomogeneity correction may provide a sensitive method for identifying the subtle regional hypodensity which is characteristic of early ischemic infarcts.

Dissipative Catalysis with a Molecular Machine.

We report on catalysis by a fuel-induced transient state of a synthetic molecular machine. A [2]rotaxane molecular shuttle containing secondary ammonium/amine and thiourea stations is converted between catalytically inactive and active states by pulses of a chemical fuel (trichloroacetic acid), which is itself decomposed by the machine and/or the presence of additional base. The ON-state of the rotaxane catalyzes the reduction of a nitrostyrene by transfer hydrogenation.

A Radiodensity Histogram Study of the Brain in Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive neurodegenerative disease, affecting 1 million Americans and 2.5 million people globally. Although the diagnosis is made clinically, imaging plays a major role in diagnosing and monitoring disease progression and treatment response.