DNA-PAINT Probe Modifications Support High-Resolution Imaging with Shorter Binding Domains.

DNA-based Points Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) is an effective super resolution microscopy technique, and its optimization is key to improve nanoscale detection. The state-of-the-art improvements that are at the base of this optimization have been first routinely validated on DNA nanostructure devices before being tested on biological samples. This allows researchers to finely tune DNA-PAINT imaging features in a more controllable environment.

Update on X-ray Microcalorimeter Arrays Based on Thermal MKIDs (TKIDs).

We report progress on the development of x-ray microcalorimeter thermal kinetic inductance detector (TKID) arrays, where each TKID is an independent pixel. Our goal in developing this detector technology is to arrive at high quantum efficiency, high fill factor, large-format, moderate energy resolution x-ray detector array which can be readily scaled to tens of kilo-pixels, to be used as an x-ray imaging spectrograph for astronomy and metrology applications. We discuss the evolution of the design, how it has been driven by fabrication related constraints, and the resulting impacts on detector performance.

Treatment of Organophosphorus Poisoning with 6-Alkoxypyridin-3-ol Quinone Methide Precursors: Resurrection of Methylphosphonate-Aged Acetylcholinesterase.

Organophosphorus (OP) nerve agents inhibit acetylcholinesterase (AChE), creating a cholinergic crisis in which death can occur. The phosphylated serine residue spontaneously dealkylates to the OP-aged form, which current therapeutics cannot reverse. Soman's aging half-life is 4.

Characterizing the dark count rate of a large-format MKID array.

We present an empirical measurement of the dark count rate seen in a large-format MKID array identical to those currently in use at observatories such as Subaru on Maunakea. This work provides compelling evidence for their utility in future experiments that require low-count rate, quiet environments such as dark matter direct detection. Across the bandpass from 0.

Our Souls Look Back and Wonder: Reflections on Belonging and Being Invisible in Medicine.

Addressing the unequal impact of health disparities on historically marginalized communities is a top public health priority. Diversifying the work force has been lauded as key to addressing this challenge. Contributing to diversity in the workforce is the recruitment and retention of health professionals previously excluded and underrepresented in medicine.

Membraneless Phonon Trapping and Resolution Enhancement in Optical Microwave Kinetic Inductance Detectors.

Microwave kinetic inductance detectors (MKIDs) sensitive to light in the ultraviolet to near-infrared wavelengths are superconducting microresonators that are capable of measuring photon arrival times to microsecond precision and estimating each photon's energy. The resolving power of nonmembrane MKIDs has remained stubbornly around 10 at 1  μm despite significant improvements in the system noise. Here we show that the resolving power can be roughly doubled with a simple bilayer design without needing to place the device on a membrane, avoiding a significant increase in fabrication complexity.

Does the AAMC's Definition of "Underrepresented in Medicine" Promote Justice and Inclusivity?

In 2003, the Association of American Medical Colleges reframed the concept as (URiM), which defines representation in medicine relative to representation in the US population. Schools are permitted to construct URiM definitions, suggesting the importance of regarding them as fluid works in progress as US demographics evolve. Where medical school admissions processes consider applicants' backgrounds and experiences of identity minoritization to be valuable, progress toward inclusive representation has been made.

An alternative approach to nucleic acid memory.

DNA is a compelling alternative to non-volatile information storage technologies due to its information density, stability, and energy efficiency. Previous studies have used artificially synthesized DNA to store data and automated next-generation sequencing to read it back. Here, we report digital Nucleic Acid Memory (dNAM) for applications that require a limited amount of data to have high information density, redundancy, and copy number.

A mapping review of sacrococcygeal pilonidal sinus disease.

Background: Pilonidal sinus is a hole in the natal cleft which may cause severe pain and become infected. The evidence base for management of pilonidal sinus is said to be poor quality, poorly focused and rapidly proliferating. We undertook a systematic mapping review to provide a broad overview of the field and support the identification of research priorities.

Bridging the Gap: Including Patient Voices in Short-Term Medical Mission Evaluations.

Background: Several studies have evaluated short term medical missions (STMM), but most have been from the perspective of the STMM teams providing their own suggestions [1]; few surveys have assessed the perceptions of patients who seek medical care at these STMM clinics [2].

Objectives: This project evaluates the efficiency, quality, and value of the services provided by a STMM clinic established in the community of Paraíso in Santo Domingo Norte, Dominican Republic, as perceived by the patients. Study results will allow organizers to make improvements to these clinics and will contribute to a broader understanding of the benefit and value of medical services provided by STMMs.

Ultralow effective work function surfaces using diamondoid monolayers.

Electron emission is critical for a host of modern fabrication and analysis applications including mass spectrometry, electron imaging and nanopatterning. Here, we report that monolayers of diamondoids effectively confer dramatically enhanced field emission properties to metal surfaces. We attribute the improved emission to a significant reduction of the work function rather than a geometric enhancement.

Physical properties of materials derived from diamondoid molecules.

Diamondoids are small hydrocarbon molecules which have the same rigid cage structure as bulk diamond. They can be considered the smallest nanoparticles of diamond. They exhibit a mixture of properties inherited from bulk cubic diamond as well as a number of unique properties related to their size and structure.

Cloning and pharmacological characterization of the dog P2X7 receptor.

Background And Purpose: Human and rodent P2X7 receptors exhibit differences in their sensitivity to antagonists. In this study we have cloned and characterized the dog P2X7 receptor to determine if its antagonist sensitivity more closely resembles the human or rodent orthologues.

Experimental Approach: A cDNA encoding the dog P2X7 receptor was isolated from a dog heart cDNA library, expressed in U-2 OS cells using the BacMam viral expression system and characterized in electrophysiological, ethidium accumulation and radioligand binding studies.

Mechanism of action of species-selective P2X(7) receptor antagonists.

Background And Purpose: AZ11645373 and N-{2-methyl-5-[(1R, 5S)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-ylcarbonyl]phenyl}-2-tricyclo[3.

Origin of the monochromatic photoemission peak in diamondoid monolayers.

Recent photoemission experiments have discovered a highly monochromatized secondary electron peak emitted from diamondoid self-assembled monolayers on metal substrates. New experimental data and simulation results are presented to show that a combination of negative electron affinity and strong electron-phonon scattering is responsible for this behavior. The simulation results are generated using a simple Monte Carlo transport algorithm.

Identification of regions of the P2X(7) receptor that contribute to human and rat species differences in antagonist effects.

Background And Purpose: Several P2X(7) receptor antagonists are allosteric inhibitors and exhibit species difference in potency. Furthermore, N(2)-(3,4-difluorophenyl)-N(1)-(2-methyl-5-(1-piperazinylmethyl)phenyl)glycinamide dihydrochloride (GW791343) exhibits negative allosteric effects at the human P2X(7) receptor but is a positive allosteric modulator of the rat P2X(7) receptor. In this study we have identified several regions of the P2X(7) receptor that contribute to the species differences in antagonist effects.

Cloning and pharmacological characterization of the guinea pig P2X7 receptor orthologue.

Background And Purpose: The human, rat, and mouse P2X(7) receptors have been previously characterized, and in this study we report the cloning and pharmacological properties of the guinea pig orthologue.

Experimental Approach: A cDNA encoding for the guinea pig P2X(7) receptor was isolated from a guinea pig brain library. The receptor was expressed in U-2 OS cells using the BacMam viral expression system.

Detection of a microRNA signal in an in vivo expression set of mRNAs.

Background: microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of a miRNA to the target mRNA. As a result, translation of the target mRNA is inhibited and the mRNA may be destabilized.

Direct labelling of the human P2X7 receptor and identification of positive and negative cooperativity of binding.

Background And Purpose: The P2X(7) receptor exhibits complex pharmacological properties. In this study, binding of a [(3)H]-labelled P2X(7) receptor antagonist to human P2X(7) receptors has been examined to further understand ligand interactions with this receptor.

Experimental Approach: The P2X(7) receptor antagonist, N-[2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2-tricyclo[3.

Evaluation of cell-based assays for steroid nuclear receptors delivered by recombinant baculoviruses.

The authors describe the use of modified baculoviruses containing mammalian expression cassettes (BacMam technology) in steroid nuclear receptor reporter assays designed for screening and profiling agonist and antagonist compounds. Baculo-viruses were constructed that express full-length human genes for mineralocorticoid receptor (MR), glucocorticoid receptor (GR), progesterone receptor A (PR-A), and progesterone receptor B (PR-B) from the cytomegalovirus immediate early promoter. A virus carrying the mouse mammary tumor virus-firefly luciferase (MMTV-Luc) cassette was generated to provide a suitable reporter construct.

Recombinant baculoviruses used to study estrogen receptor function in human osteosarcoma cells.

We report that modified baculoviruses, termed BacMam viruses, can efficiently deliver multiple genes into mammalian cells to generate a heterologous transcription factor/reporter gene system. Using human estrogen receptor (ER) as a model nuclear receptor, we demonstrate how this approach can be successfully applied to assay development in Saos-2 human osteosarcoma cells. BacMam viruses containing full-length cDNAs were constructed for both human ER subtypes, ERalpha and ERbeta, and a third BacMam virus containing an ER-responsive reporter gene cassette.

Development of a novel high-throughput surrogate assay to measure HIV envelope/CCR5/CD4-mediated viral/cell fusion using BacMam baculovirus technology.

The initial event by which M-tropic HIV strains gain access to cells is via interaction of the viral envelope protein gp120 with the host cell CCR5 coreceptor and CD4. Inhibition of this event reduces viral fusion and entry into cells in vitro. The authors have employed BacMam baculovirus-mediated gene transduction to develop a cell/cell fusion assay that mimics the HIV viral/cell fusion process and allows high-throughput quantification of this fusion event.