969 research outputs found
Enhancing Post-Hoc Explanation Benchmark Reliability for Image Classification
Deep neural networks, while powerful for image classification, often operate
as "black boxes," complicating the understanding of their decision-making
processes. Various explanation methods, particularly those generating saliency
maps, aim to address this challenge. However, the inconsistency issues of
faithfulness metrics hinder reliable benchmarking of explanation methods. This
paper employs an approach inspired by psychometrics, utilizing Krippendorf's
alpha to quantify the benchmark reliability of post-hoc methods in image
classification. The study proposes model training modifications, including
feeding perturbed samples and employing focal loss, to enhance robustness and
calibration. Empirical evaluations demonstrate significant improvements in
benchmark reliability across metrics, datasets, and post-hoc methods. This
pioneering work establishes a foundation for more reliable evaluation practices
in the realm of post-hoc explanation methods, emphasizing the importance of
model robustness in the assessment process
A survey of the protective effects of some commercially available antioxidant supplements in genetically and chemically induced models of oxidative stress in Drosophila melanogaster
AbstractOxidative stress remains one of the most well studied, albeit somewhat contentious, causes of age-related changes in humans. Consequently, a large number of putative antioxidant compounds are freely available in myriad formulations that are often not tested for their efficacy or regulated for quality control. Following the development of a Drosophila model of oxidative-stress dependent aging (p38 MAP K (p38K) mutants) in our laboratory, we attempted to test the protective effect of some of these commonly available formulations against oxidative stress, in the p38K model. As environmental exposure to oxidizing toxins has been linked to a variety of human diseases, we also tested the efficacy of these supplements on chemically-induced models of oxidative stress (paraquat and hydrogen peroxide exposure). Our results suggest that when added as a dietary supplement, some of these over-the-counter compounds, notably containing açai extracts, confer significant protection for both the p38K-dependent genetic model as well as the toxin-induced model. These products were also remarkably effective at dampening stress-induced expression of the detoxifying enzyme GSTD1 and eliminating paraquat induced circadian rhythm deficits. Overall, our results suggest potential benefits of dietary supplementation with some of these compounds, especially under conditions of elevated oxidative stress. These findings should be assessed in the context of other studies that seek to identify active principles in these extracts, determine their effective dosage for human consumption and evaluate the safety of long-term prophylactic applications
Safe Crossover of Neural Networks Through Neuron Alignment
One of the main and largely unexplored challenges in evolving the weights of
neural networks using genetic algorithms is to find a sensible crossover
operation between parent networks. Indeed, naive crossover leads to
functionally damaged offspring that do not retain information from the parents.
This is because neural networks are invariant to permutations of neurons,
giving rise to multiple ways of representing the same solution. This is often
referred to as the competing conventions problem. In this paper, we propose a
two-step safe crossover(SC) operator. First, the neurons of the parents are
functionally aligned by computing how well they correlate, and only then are
the parents recombined. We compare two ways of measuring relationships between
neurons: Pairwise Correlation (PwC) and Canonical Correlation Analysis (CCA).
We test our safe crossover operators (SC-PwC and SC-CCA) on MNIST and CIFAR-10
by performing arithmetic crossover on the weights of feed-forward neural
network pairs. We show that it effectively transmits information from parents
to offspring and significantly improves upon naive crossover. Our method is
computationally fast,can serve as a way to explore the fitness landscape more
efficiently and makes safe crossover a potentially promising operator in future
neuroevolution research and applications
Strong and tunable mode coupling in carbon nanotube resonators
The non-linear interaction between two mechanical resonances of the same
freely suspended carbon nanotube resonator is studied. We find that in the
Coulomb blockade regime, the non-linear modal interaction is dominated by
single-electron-tunneling processes, and that the mode-coupling parameter can
be tuned with the gate voltage, allowing both mode softening and mode
stiffening behavior. This is in striking contrast to tension-induced mode
coupling in strings, where the coupling parameter is positive and gives rise to
a stiffening of the mode. The strength of the mode coupling in carbon nanotubes
in the Coulomb blockade regime is observed to be six orders of magnitude larger
than the mechanical mode coupling in micromechanical resonators.Comment: 8 pages, 4 figure
Lipoproteína (a) y oligonucleótidos antisentido
Contexto: la Lipoproteína(a) (Lp(a)) fue descrita por primera vez por el genetista Kare Berg en 1963, aislada como un nuevo antígeno (en suero humano), asociada al colesterol de lipoproteínas de baja densidad. Posteriormente se reportó que sus niveles son determinados genéticamente y genera mayor riesgo de desarrollar aterosclerosis. En los últimos 20 años se ha incrementado la evidencia acerca de la estructura, genética y papel metabólico de la Lp(a), además de las posibles terapias para disminuir su aterogenicidad.
Objetivo: aportar información sobre el papel de la Lp(a) en la enfermedad aterosclerótica y evaluar la nueva evidencia acerca de las terapias actuales, principalmente el papel de los oligonucleótidos antisentido.
Metodología: revisión de la literatura en la base de datos PubMed, Google académico y literatura gris utilizando los términos MeSH: “lipoprotein(a)”, “atherosclerosis”, “physiopathology”, “therapeutics”, “drug therapy”, “oligonucleotides, antisense” y por revisión del listado de referencias bibliográficas (en “bola de nieve”) de los estudios seleccionados.
Resultados: existe gran variedad de evidencia bibliográfica acerca de la Lp(a), su importancia en el desarrollo de enfermedad arteriosclerótica, y las múltiples opciones farmacológicas tanto aprobadas como en desarrollo usando esta molécula como diana terapéutica.
Conclusiones: el entendimiento de la Lp(a) trae nuevas respuestas acerca de la enfermedad cardiovascular aterosclerótica; actualmente se encuentra en desarrollo farmacológico los oligonucleótidos antisentido, propuestos como una terapia prometedora para la modificación de sus niveles, sin embargo, es necesario esperar los desenlaces de la fase III de los ensayos para confirmar resultados preliminares
Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells
COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display abnormalities. LMSCs were isolated from lung tissue of severe COPD patients and non-COPD controls. Effects of LMSC conditioned-medium (CM) on H(2)O(2)-induced, electric field- and scratch-injury were studied in A549 and NCI-H441 epithelial cells. In organoid models, LMSCs were co-cultured with NCI-H441 or primary lung cells. Organoid number, size and expression of alveolar type II markers were assessed. Pre-treatment with LMSC-CM significantly attenuated oxidative stress-induced necrosis and accelerated wound repair in A549. Co-culture with LMSCs supported organoid formation in NCI-H441 and primary epithelial cells, resulting in significantly larger organoids with lower type II-marker positivity in the presence of COPD-derived versus control LMSCs. Similar abnormalities developed in organoids from COPD compared to control-derived lung cells, with significantly larger organoids. Collectively, this indicates that LMSCs’ secretome attenuates alveolar epithelial injury and supports epithelial repair. Additionally, LMSCs promote generation of alveolar organoids, with abnormalities in the supportive effects of COPD-derived LMCS, reflective of impaired regenerative responses of COPD distal lung cells
Leader heuristics, political knowledge and voting in Britain's AV referendum
This paper uses data gathered in the British Election Study's 2011 AV Referendum Survey to investigate the impact of party leader images on referendum voting. The emphasis on leader images accords well with research showing that leader heuristics have sizable effects on voting in major referendums and general elections in Britain and other mature democracies. Reacting to these findings, some analysts have argued that the effects of leader images are heterogeneous, being stronger for voters with lower levels of political knowledge. In contrast, consistent with recent research in experimental economics and political psychology, it can be hypothesized that more knowledgeable voters rely more heavily on leader heuristics than do less knowledgeable individuals. Using multivariate statistical techniques developed for interpreting interaction effects in nonlinear models, analyses indicate that a political knowledge index focusing on the electoral system does not have statistically significant effects on referendum voting. However, voters' knowledge of leaders' positions on AV does interact with leader images. The analyses show that voters with higher levels of political knowledge are influenced more strongly by leader heuristics than are those who are less knowledgeable. © 2012 Elsevier Ltd
Baseline Characteristics of Sars-Cov-2 Vaccine Non-Responders in a Large Population-Based Sample
INTRODUCTION: Studies indicate that individuals with chronic conditions and specific baseline characteristics may not mount a robust humoral antibody response to SARS-CoV-2 vaccines. In this paper, we used data from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a longitudinal state-wide seroprevalence program that has enrolled more than 90,000 participants, to evaluate the role of chronic diseases as the potential risk factors of non-response to SARS-CoV-2 vaccines in a large epidemiologic cohort.
METHODS: A participant needed to complete an online survey and a blood draw to test for SARS-CoV-2 circulating plasma antibodies at four-time points spaced at least three months apart. Chronic disease predictors of vaccine non-response are evaluated using logistic regression with non-response as the outcome and each chronic disease + age as the predictors.
RESULTS: As of April 24, 2023, 18,240 participants met the inclusion criteria; 0.58% (N = 105) of these are non-responders. Adjusting for age, our results show that participants with self-reported immunocompromised status, kidney disease, cancer, and other non-specified comorbidity were 15.43, 5.11, 2.59, and 3.13 times more likely to fail to mount a complete response to a vaccine, respectively. Furthermore, having two or more chronic diseases doubled the prevalence of non-response.
CONCLUSION: Consistent with smaller targeted studies, a large epidemiologic cohort bears the same conclusion and demonstrates immunocompromised, cancer, kidney disease, and the number of diseases are associated with vaccine non-response. This study suggests that those individuals, with chronic diseases with the potential to affect their immune system response, may need increased doses or repeated doses of COVID-19 vaccines to develop a protective antibody level
Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors.
The Cre-loxP system is invaluable for spatial and temporal control of gene knockout, knockin, and reporter expression in the mouse nervous system. However, we report varying probabilities of unexpected germline recombination in distinct Cre driver lines designed for nervous system-specific recombination. Selective maternal or paternal germline recombination is showcased with sample Cre lines. Collated data reveal germline recombination in over half of 64 commonly used Cre driver lines, in most cases with a parental sex bias related to Cre expression in sperm or oocytes. Slight differences among Cre driver lines utilizing common transcriptional control elements affect germline recombination rates. Specific target loci demonstrated differential recombination; thus, reporters are not reliable proxies for another locus of interest. Similar principles apply to other recombinase systems and other genetically targeted organisms. We hereby draw attention to the prevalence of germline recombination and provide guidelines to inform future research for the neuroscience and broader molecular genetics communities
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