Understanding Travel Considerations and Barriers for People with Disabilities to Using Current Modes of Transportation Through Journey Mapping.

This study aimed to apply a journey mapping methodology to identify travel considerations and barriers for people with disabilities (PWDs) at each travel stage, from considering a trip through to arriving at the destination for their current modes of transportation, with the objective of understanding and avoiding "pain points" during a transition to autonomous driving systems. Twenty PWDs, including those with physical, visual, aural, cognitive, and combined physical/visual impairments, participated in a semistructured one-on-one interview. Descriptive statistics were used for demographic information, and qualitative content analysis was used to analyze the transcribed interviews and extract themes.

Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism.

Purine nucleotides play central roles in energy metabolism in the heart. Most fundamentally, the free energy of hydrolysis of the adenine nucleotide adenosine triphosphate (ATP) provides the thermodynamic driving force for numerous cellular processes including the actin-myosin crossbridge cycle. Perturbations to ATP supply and/or demand in the myocardium lead to changes in the homeostatic balance between purine nucleotide synthesis, degradation, and salvage, potentially affecting myocardial energetics and, consequently, myocardial mechanics.

Higher mitochondrial oxidative capacity is the primary molecular differentiator in muscle of rats with high and low intrinsic cardiorespiratory fitness.

Objective: Cardiorespiratory fitness (CRF) is tightly linked with health and longevity and is implicated in metabolic flexibility and substrate metabolism. The high capacity runner (HCR) and low capacity runner (LCR) rat lines are a genetically heterogeneous rat model selected and bred for CRF that reflect CRF in humans by exhibiting differences in nutrient handling. This study aims to differentiate the intrinsic substrate preference of the HCR compared to LCR rats to better understand the intersection of mitochondrial respiration and intrinsic CRF.

Donor-Acceptor Pyridinium Salts for Photo-Induced Electron-Transfer-Driven Modification of Tryptophan in Peptides, Proteins, and Proteomes Using Visible Light.

Tryptophan (Trp) plays a variety of critical functional roles in protein biochemistry; however, owing to its low natural frequency and poor nucleophilicity, the design of effective methods for both single protein bioconjugation at Trp as well as for chemoproteomic profiling remains a challenge. Here, we report a method for covalent Trp modification that is suitable for both scenarios by invoking photo-induced electron transfer (PET) as a means of driving efficient reactivity. We have engineered biaryl -carbamoyl pyridinium salts that possess a donor-acceptor relationship that enables optical triggering with visible light whilst simultaneously attenuating the probe's photo-oxidation potential in order to prevent photodegradation.

Functional proteomics approach to investigate the biological activities of cDNAs implicated in breast cancer.

Functional proteomics approaches that comprehensively evaluate the biological activities of human cDNAs may provide novel insights into disease pathogenesis. To systematically investigate the functional activity of cDNAs that have been implicated in breast carcinogenesis, we generated a collection of cDNAs relevant to breast cancer, the Breast Cancer 1000 (BC1000), and conducted screens to identify proteins that induce phenotypic changes that resemble events which occur during tumor initiation and progression. Genes were selected for this set using bioinformatics and data mining tools that identify genes associated with breast cancer.

G1/S cell cycle arrest provides anoikis resistance through Erk-mediated Bim suppression.

Proper attachment to the extracellular matrix is essential for cell survival. Detachment from the extracellular matrix results in an apoptotic process termed anoikis. Anoikis induction in MCF-10A mammary epithelial cells is due not only to loss of survival signals following integrin disengagement, but also to consequent downregulation of epidermal growth factor (EGFR) and loss of EGFR-induced survival signals.

The role of apoptosis in creating and maintaining luminal space within normal and oncogene-expressing mammary acini.

We have utilized in vitro three-dimensional epithelial cell cultures to analyze the role of apoptosis in the formation and maintenance of a hollow glandular architecture. Lumen formation is associated with the selective apoptosis of centrally located cells; this apoptosis follows apicobasal polarization and precedes proliferative suppression during acinar development. Notably, either inhibiting apoptosis (by exogenously expressing antiapoptotic Bcl family proteins) or enhancing proliferation (via Cyclin D1 or HPV E7 overexpression) does not result in luminal filling, suggesting glandular architecture is resistant to such isolated oncogenic insults.