Publications by authors named "Wheeler N"

Rationale: group bacteria (MABS) cause lethal infections in people with chronic lung diseases. Transmission mechanisms remain poorly understood; the detection of dominant circulating clones (DCCs) has suggested potential for person-to-person transmission.

Objectives: This study aimed to determine the role of drinking water in the transmission of MABS.

View Article and Find Full Text PDF

The integration of artificial intelligence (AI) in protein design presents unparalleled opportunities for innovation in bioengineering and biotechnology. However, it also raises significant biosecurity concerns. This review examines the changing landscape of bioweapon risks, the dual-use potential of AI-driven bioengineering tools, and the necessary safeguards to prevent misuse while fostering innovation.

View Article and Find Full Text PDF

Through selective breeding, humans have driven exceptional morphological diversity in domestic dogs, creating more than 200 recognized breeds developed for specialized functional tasks such as herding, protection, and hunting. Here, we use three-dimensional reconstructions of dog skulls to ask whether these function-oriented kennel-club groups reflect differences in morphology that correspond to those functions. We analyzed 117 canid skulls, representing 40 domestic dog breeds and 18 wild subspecies, using geometric morphometric techniques and -means clustering.

View Article and Find Full Text PDF

Hollow-core optical fiber (HCF) gas cells are an attractive option for many applications including metrology and non-linear optics due to the enhanced gas-light interaction length in a compact and lightweight format. Here, we report the first demonstration and characterization of a selectively pressurized, hermetically sealed hollow-core fiber-based gas cell, where the core is filled with a higher gas pressure than the cladding to enhance the optical performance. This differential gas pressure creates a gas-induced differential refractive index (GDRI) that is shown to enable significant modification of the HCF's optical performance.

View Article and Find Full Text PDF

The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's Disease and Related Dementias (AD/ADRD) by sequencing whole genomes of affected participants and age-matched cognitive controls from diverse populations. The Genome Center for Alzheimer's Disease (GCAD) processed whole-genome sequencing data from 36,361 ADSP participants, including 35,014 genetically unique participants of which 45% are from non-European ancestry, across 17 cohorts in 14 countries in this fourth release (R4). This sequencing effort identified 387 million bi-allelic variants, 42 million short insertions/deletions, and 2.

View Article and Find Full Text PDF

Age-related macular degeneration (AMD) is a leading cause of blindness with $344 billion dollars global costs. In 2016, the International Age-related Macular Degeneration Genomics Consortium devised genomic data on ∼50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD in European ancestry.

View Article and Find Full Text PDF

White matter lesions (WMLs) are prevalent with aging, and higher WML burden has been observed in older adults with vascular diseases. While the physiology underlying the formation of WMLs is not known, various risk factors are associated with high WML burden. Here, we investigated the relationship between vascular risk factors and microvascular physiology (i.

View Article and Find Full Text PDF
Article Synopsis
  • - The study aims to improve the accuracy of screening DNA synthesis orders to identify potentially dangerous sequences by creating a prototype test dataset that sets a baseline for various screening methods.
  • - The methodology involved screening sequences from different groups of controlled organisms and analyzing discrepancies between various screening tools, showcasing challenges in defining risk and regulatory controls.
  • - The findings reveal the need for better collaboration between experts and regulators, suggesting a shift from species-specific to function-oriented regulatory practices, which could enhance safety and oversight in DNA synthesis.
View Article and Find Full Text PDF

Relationship education has shown promising effects for low-income couples on outcomes such as promoting positive communication, improving global relationship satisfaction, parenting, and individual psychological distress. Studies also indicate that couples' baseline distress (e.g.

View Article and Find Full Text PDF

We introduce a flexible microscale all-fiber-optic Raman probe which can be embedded into devices to enable operando in situ spectroscopy. The facile-constructed probe is composed of a nested antiresonant nodeless hollow-core fiber combined with an integrated high refractive index barium titanate microlens. Pump laser 785 nm excitation and near-infrared collection are independently characterized, demonstrating an excitation spot of full-width-half-maximum 1.

View Article and Find Full Text PDF

Introduction: Nucleic acid synthesis is a powerful tool that has revolutionized the life sciences. However, the misuse of synthetic nucleic acids could pose a serious threat to public health and safety. There is a need for international standards for nucleic acid synthesis screening to help prevent the misuse of this technology.

View Article and Find Full Text PDF

Pharmaceutical manufacturing utilizes solvents at different stages of production. Some of the harmful solvent residuals may be retained in the final product; therefore, they need to be monitored for quality control and to meet the regulation requirement. Here, a novel method capable of rapidly analyzing residual solvents in pharmaceutical products was developed using a compact-portable gas chromatography with a photoionization detector (GC-PID).

View Article and Find Full Text PDF

Introduction: As the body's first line of defense against disease and infection, neutrophils must efficiently navigate to sites of inflammation; however, neutrophil dysregulation contributes to the pathogenesis of numerous diseases that leave people susceptible to infections. Many of these diseases are also associated with changes to the protein composition of the extracellular matrix. While it is known that neutrophils and endothelial cells, which play a key role in neutrophil activation, are sensitive to the mechanical and structural properties of the extracellular matrix, our understanding of how protein composition in the matrix affects the neutrophil response to infection is incomplete.

View Article and Find Full Text PDF

When a hollow core fiber is drawn, the core and cladding holes within the internal cane geometry are pressurized with an inert gas to enable precise control over the internal microstructure of the fiber and counteract surface tension forces. Primarily by considering the temperature drop as the fiber passes through the furnace and the geometrical transformation of the internal microstructure from preform-to-fiber, we recently established that the gas pressure within the final 'as-drawn' fiber is substantially below atmospheric pressure. We have also established that slight changes in the gas refractive index within the core and surrounding cladding holes induced by changes in gas pressure are sufficient to significantly affect both the modality and loss of the fiber.

View Article and Find Full Text PDF

Label-free and multiphoton micro-endoscopy can transform clinical histopathology by providing an in situ tool for diagnostic imaging and surgical treatment in diseases such as cancer. Key to a multiphoton imaging-based micro-endoscopic device is the optical fiber, for distortion-free and efficient delivery of ultra-short laser pulses to the sample and effective signal collection. In this work, we study a new hollow-core (air-filled) double-clad anti-resonant fiber (DC-ARF) as a high-performance candidate for multiphoton micro-endoscopy.

View Article and Find Full Text PDF

Background: Tertiary Lymphoid Structures (TLS) correlate with positive outcomes in patients with NSCLC and the efficacy of immune checkpoint blockade (ICB) in cancer. The actin regulatory protein hMENA undergoes tissue-specific splicing, producing the epithelial hMENA linked to favorable prognosis in early NSCLC, and the mesenchymal hMENAΔv6 found in invasive cancer cells and pro-tumoral cancer-associated fibroblasts (CAFs). This study investigates how hMENA isoforms in tumor cells and CAFs relate to TLS presence, localization and impact on patient outcomes and ICB response.

View Article and Find Full Text PDF

The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to a joint analysis. Here we present a bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen sequencing centers in the Alzheimer's Disease Sequencing Project. The joint-genotype called variant-called format (VCF) file contains only positions within the union of capture kits.

View Article and Find Full Text PDF

This Letter reports the first, to the best of our knowledge, spectral radiation induced attenuation (RIA) measurements of nested anti-resonant nodeless hollow-core fibers (NANFs). A 5-tube NANF, alongside a solid-core single-mode radiation resistant fiber (SM-RRF), was irradiated under γ-ray up to 101 kGy (SiO) and under x-ray up to 241 kGy (SiO). No RIA was observed in the NANF in the second half of the O-band, the S-band, the C-band, and the L-band.

View Article and Find Full Text PDF

The Current food environment has become increasingly obesogenic, with rates of obesity and related conditions continually rising. Advertisements for energy-dense foods are abundant and promote unhealthy eating behaviors by capitalizing on one's attentional bias towards food cues, a cognitive process resulting from the sensitization of highly reinforcing food. A heightened awareness towards food cues may promote overconsumption of energy-dense foods.

View Article and Find Full Text PDF

Nearly a century after the beginning of the antibiotic era, which has been associated with unparalleled improvements in human health and reductions in mortality associated with infection, the dwindling pipeline for new antibiotic classes coupled with the inevitable spread of antimicrobial resistance (AMR) poses a major global challenge. Historically, surveillance of bacteria with AMR typically relied on phenotypic analysis of isolates taken from infected individuals, which provides only a low-resolution view of the epidemiology behind an individual infection or wider outbreak. Recent years have seen increasing adoption of powerful new genomic technologies with the potential to revolutionise AMR surveillance by providing a high-resolution picture of the AMR profile of the bacteria causing infections and providing real-time actionable information for treating and preventing infection.

View Article and Find Full Text PDF

Whole-genome sequencing of antimicrobial-resistant pathogens is increasingly being used for antimicrobial resistance (AMR) surveillance, particularly in high-income countries. Innovations in genome sequencing and analysis technologies promise to revolutionise AMR surveillance and epidemiology; however, routine adoption of these technologies is challenging, particularly in low-income and middle-income countries. As part of a wider series of workshops and online consultations, a group of experts in AMR pathogen genomics and computational tool development conducted a situational analysis, identifying the following under-used innovations in genomic AMR surveillance: clinical metagenomics, environmental metagenomics, gene or plasmid tracking, and machine learning.

View Article and Find Full Text PDF

Parasitic nematodes infect billions of people and are mainly controlled by anthelmintic mass drug administration (MDA). While there are growing efforts to better understand mechanisms of anthelmintic resistance in human and animal populations, it is unclear how resistance mechanisms that alter susceptibility to one drug affect the interactions and efficacy of drugs used in combination. Mutations that alter drug permeability across primary nematode barriers have been identified as potential resistance mechanisms using the model nematode Caenorhabditis elegans.

View Article and Find Full Text PDF

Introduction: The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site Alzheimer's Genomics Database (GenomicsDB) is a public knowledge base of Alzheimer's disease (AD) genetic datasets and genomic annotations.

Methods: GenomicsDB uses a custom systems architecture to adopt and enforce rigorous standards that facilitate harmonization of AD-relevant genome-wide association study summary statistics datasets with functional annotations, including over 230 million annotated variants from the AD Sequencing Project.

Results: GenomicsDB generates interactive reports compiled from the harmonized datasets and annotations.

View Article and Find Full Text PDF

By exploiting the excellent short-term phase stability between consecutive pulses from a free-running optical parametric oscillator frequency comb, we report the first example of hollow-core fiber-delivered heterodyne spectroscopy in the 3.1-3.8 µm wavelength range.

View Article and Find Full Text PDF