Nine quick tips for efficient bioinformatics curriculum development and training.

Biomedical research is becoming increasingly data driven. New technologies that generate large-scale, complex data are continually emerging and evolving. As a result, there is a concurrent need for training researchers to use and understand new computational tools. Here we describe an efficient and effective approach to developing curriculum materials that can be deployed in a research environment to meet this need

Characterization of Defects and Designed Flaws in Metal Additive Manufacturing (AM) Parts with X-ray Computed Tomography (XCT)

Metal Additive Manufacturing (AM) has great potential to revolutionize manufacturing industries, but a reliable method to detect defects in AM-produced parts with complex internal structures must be developed prior to its widespread adoption. In this research, defects occurring in additively manufactured metal parts are characterized with X-ray Computed Tomography (XCT). In addition, the concept of metrological XCT is introduced, with the goal of providing more accurate dimensional measurements of the internal features. Preliminary experiments have been conducted toward the larger goal of evaluating XCT as a viable option for nondestructive evaluation of AM-produced components. Critical to this evaluation is the principle of the Probability of Detection (PoD), which has not been previously determined for typical AM defects using XCT. The first step in determining the PoD for XCT is to develop a suitable artifact with embedded features that are representative of the defects occurring in AM-produced parts. Two sets of samples were built by AM and their embedded defects measured by XCT. In the first set of samples, the chosen AM processing parameters were suboptimal, ensuring that defects would be present in the parts. These parameters were also varied to understand their effect on the resulting microstructure and defect formation. Measurements of porosity and the pore size distribution were determined from the XCT images. In the second set of samples, synthetic internal features were added, some approximating typical AM defects. Dimensional XCT was used to evaluate the quality of these features. Based on the results, a future experiment with the goal of estimating the PoD of critical AM defects with an XCT system is suggested

Diaphragm Abnormalities in Patients with End-Stage Heart Failure: NADPH Oxidase Upregulation and Protein Oxidation

Patients with heart failure (HF) have diaphragm abnormalities that contribute to disease morbidity and mortality. Studies in animals suggest that reactive oxygen species (ROS) cause diaphragm abnormalities in HF. However, the effects of HF on ROS sources, antioxidant enzymes, and protein oxidation in the diaphragm of humans is unknown. NAD(P)H oxidase, especially the Nox2 isoform, is an important source of ROS in the diaphragm. Our main hypothesis was that diaphragm from patients with HF have heightened Nox2 expression and p47phox phosphorylation (marker of enzyme activation) that is associated with elevated protein oxidation. We collected diaphragm biopsies from patients with HF and brain-dead organ donors (controls). Diaphragm mRNA levels of Nox2 subunits were increased 2.5–4.6-fold over controls (p \u3c 0.05). Patients also had increased protein levels of Nox2 subunits (p47phox, p22phox, and p67phox) and total p47phox phosphorylation, while phospho-to-total p47phox levels were unchanged. The antioxidant enzyme catalase was increased in patients, whereas glutathione peroxidase and superoxide dismutases were unchanged. Among markers of protein oxidation, carbonyls were increased by ~40% (p \u3c 0.05) and 4-hydroxynonenal and 3-nitrotyrosines were unchanged in patients with HF. Overall, our findings suggest that Nox2 is an important source of ROS in the diaphragm of patients with HF and increases in levels of antioxidant enzymes are not sufficient to maintain normal redox homeostasis. The net outcome is elevated diaphragm protein oxidation that has been shown to cause weakness in animals

The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted

Effects of a Brief Stair-Climbing Intervention on Cognitive Performance and Mood States in Healthy Young Adults

Objective: Previous studies focused on the benefits of acute exercise on cognition and mood have mostly used specialized laboratory-based equipment, thus little is known about how such protocols generalize to naturalistic settings. Stair climbing is a simple and readily accessible means of exercise that can be performed in naturalistic settings (e.g., at home or at the workplace). In the present study we examined the effects of stair-climbing intervals on subsequent cognitive performance and mood in healthy young adults. Method: Thirty-two undergraduate students (Mage = 19.4 years, SD = 1.3; 21 females) completed a controlled randomized crossover trial with session order counterbalanced across participants. Participants visited the lab on two occasions, one week apart, and completed one control session (no exercise) and one stair-climbing session (3 × 1 min stair-climbing intervals) with cognitive performance and mood assessed at the end of each session. Results: Repeated measures ANCOVA revealed that males (Hedges’ gav = 0.45) showed better switching performance following the stair climbing but females (Hedges’ gav < 0.03) did not. Participants felt more energetic (Hedges’ gav = 1.05), less tense (Hedges’ gav = 0.61), and less tired (Hedges’ gav = 0.43) following the stair climbing. In addition, higher exercise intensity during the stair climbing predicted better subsequent switching performance and higher energetic ratings. Conclusion: These findings indicate that short bouts of stair climbing in a naturalistic setting can induce cognitive benefits for more challenging tasks, albeit only in males, indicating a sex-specific effect. Short bouts of stair climbing can be a practical approach to increase feelings of energy in daily life

Characterization of Defects and Designed Flaws in Metal Additive Manufacturing (AM) Parts with X-ray Computed Tomography (XCT)

Metal Additive Manufacturing (AM) has great potential to revolutionize manufacturing industries, but a reliable method to detect defects in AM-produced parts with complex internal structures must be developed prior to its widespread adoption. In this research, defects occurring in additively manufactured metal parts are characterized with X-ray Computed Tomography (XCT). In addition, the concept of metrological XCT is introduced, with the goal of providing more accurate dimensional measurements of the internal features. Preliminary experiments have been conducted toward the larger goal of evaluating XCT as a viable option for nondestructive evaluation of AM-produced components. Critical to this evaluation is the principle of the Probability of Detection (PoD), which has not been previously determined for typical AM defects using XCT. The first step in determining the PoD for XCT is to develop a suitable artifact with embedded features that are representative of the defects occurring in AM-produced parts. Two sets of samples were built by AM and their embedded defects measured by XCT. In the first set of samples, the chosen AM processing parameters were suboptimal, ensuring that defects would be present in the parts. These parameters were also varied to understand their effect on the resulting microstructure and defect formation. Measurements of porosity and the pore size distribution were determined from the XCT images. In the second set of samples, synthetic internal features were added, some approximating typical AM defects. Dimensional XCT was used to evaluate the quality of these features. Based on the results, a future experiment with the goal of estimating the PoD of critical AM defects with an XCT system is suggested.</p

Nine quick tips for efficient bioinformatics curriculum development and training.

Biomedical research is becoming increasingly data driven. New technologies that generate large-scale, complex data are continually emerging and evolving. As a result, there is a concurrent need for training researchers to use and understand new computational tools. Here we describe an efficient and effective approach to developing curriculum materials that can be deployed in a research environment to meet this need

Does Visual Subordinate-Level Categorization Engage The Functionally-Defined Fusiform Face Area?

Functional magnetic resonance imaging was used to compare brain activation associated with basic-level #e.g., BIRD# and subordinate-level #e.g., EAGLE# processing for both visual and semantic judgments. We localized the putative face area for eleven subjects, who also performed visual matching judgments for pictures and aurally-presented words. The middle fusiform and occipital gyri were recruited for subordinate minus basic visual judgments, re#ecting additional perceptual processing. When the face area was localized individually for each subject, analyses in the middle fusiform gyri revealed that subordinate-level processing activated the individual&apos;s face area. We propose that what is unique about the way faces engage this region is the focal spatial distribution of the activation rather than the recruitment of the face area per se. Eight subjects also performed semantic judgments on aurally-presented basic- and subordinate-level words. The parahippocampal gyri were more activated f..