Variance-based sensitivity of Bayesian inverse problems to the prior distribution

The formulation of Bayesian inverse problems involves choosing prior distributions; choices that seem equally reasonable may lead to significantly different conclusions. We develop a computational approach to better understand the impact of the hyperparameters defining the prior on the posterior statistics of the quantities of interest. Our approach relies on global sensitivity analysis (GSA) of Bayesian inverse problems with respect to the hyperparameters defining the prior. This, however, is a challenging problem--a naive double loop sampling approach would require running a prohibitive number of Markov chain Monte Carlo (MCMC) sampling procedures. The present work takes a foundational step in making such a sensitivity analysis practical through (i) a judicious combination of efficient surrogate models and (ii) a tailored importance sampling method. In particular, we can perform accurate GSA of posterior prediction statistics with respect to prior hyperparameters without having to repeat MCMC runs. We demonstrate the effectiveness of the approach on a simple Bayesian linear inverse problem and a nonlinear inverse problem governed by an epidemiological model

Pac-Sim: Simulation of Multi-threaded Workloads using Intelligent, Live Sampling

High-performance, multi-core processors are the key to accelerating workloads in several application domains. To continue to scale performance at the limit of Moore's Law and Dennard scaling, software and hardware designers have turned to dynamic solutions that adapt to the needs of applications in a transparent, automatic way. For example, modern hardware improves its performance and power efficiency by changing the hardware configuration, like the frequency and voltage of cores, according to a number of parameters such as the technology used, the workload running, etc. With this level of dynamism, it is essential to simulate next-generation multi-core processors in a way that can both respond to system changes and accurately determine system performance metrics. Currently, no sampled simulation platform can achieve these goals of dynamic, fast, and accurate simulation of multi-threaded workloads. In this work, we propose a solution that allows for fast, accurate simulation in the presence of both hardware and software dynamism. To accomplish this goal, we present Pac-Sim, a novel sampled simulation methodology for fast, accurate sampled simulation that requires no upfront analysis of the workload. With our proposed methodology, it is now possible to simulate long-running dynamically scheduled multi-threaded programs with significant simulation speedups even in the presence of dynamic hardware events. We evaluate Pac-Sim using the multi-threaded SPEC CPU2017, NPB, and PARSEC benchmarks with both static and dynamic thread scheduling. The experimental results show that Pac-Sim achieves a very low sampling error of 1.63% and 3.81% on average for statically and dynamically scheduled benchmarks, respectively. Pac-Sim also demonstrates significant simulation speedups as high as 523.5$\times$ (210.3$\times$ on average) for the train input set of SPEC CPU2017.Comment: 14 pages, 14 figure

Cytomegalovirus erosive gastritis in a healthy infant: update about a case

El citomegalovirus es un virus ADN de la familia Herpesviridae que puede afectar al tubo digestivo. Dentro de éste, las dianas de afectación suelen ser el colon, el esófago y el estómago. Se ha descrito ampliamente su asociación con el síndrome de Ménétrier (hiperplasia foveolar con pérdida de proteínas), si bien también puede producir cuadros de gastritis erosiva. En el presente artículo se describe un caso de gastritis erosiva en una lactante sana de 4 meses de edad, que se inició en forma de hemorragia digestiva alta. A partir de este caso, se lleva a cabo una puesta al día de este subgrupo de infecciones por citomegalovirusCytomegalovirus is a DNA Herpesviridae family which can affect the digestive tract. From the standpoint of the stomach, has been widely described his association with Ménétrier syndrome (foveolar hyperplasia with protein-losing) but can also produce erosive gastritis. This article describes a case of erosive gastritis in a healthy 4 months infant which debuted as upper gastrointestinal bleeding. In addition we perform an update of this subgroup of cytomegalovirus infection

Multiple roles of GluN2D-containing NMDA receptors in short-term potentiation and long-term potentiation in mouse hippocampal slices

The GluN2 subunits of N-methyl-d-aspartate receptors (NMDARs) are key drivers of synaptic plasticity in the brain, where the particular GluN2 composition endows the NMDAR complex with distinct pharmacological and physiological properties. Compared to GluN2A and GluN2B subunits, far less is known about the role of the GluN2D subunit in synaptic plasticity. In this study, we have used a GluN2C/2D selective competitive antagonist, UBP145, in combination with a GluN2D global knockout (GluN2D KO) mouse line to study the contribution of GluN2D-containing NMDARs to short-term potentiation (STP) and long-term potentiation (LTP) in the CA1 region of mouse hippocampal slices. We made several distinct observations: First, GluN2D KO mice have higher levels of LTP compared to wild-type (WT) mice, an effect that was occluded by blockade of GABA receptor-mediated inhibition or by using a strong LTP induction protocol. Second, UBP145 partially inhibited LTP in WT but not GluN2D KO mice. Third, UBP145 inhibited a component of STP, termed STP2, in WT but not GluN2D KO mice. Taken together, these findings suggest an involvement for GluN2D-containing NMDARs in both STP and LTP in mouse hippocampus

Combined Cisplatinum and Laser Thermal Therapy for Palliation of Recurrent Head and Neck Tumors

In recent years endoscopically controlled laser-induced thermal therapy (LITT) has been increasingly accepted as a minimally invasive method for palliation of advanced or recurrent head and neck or gastrointestinal cancer. Previous studies have shown that adjuvant chemotherapy can potentiate endoscopic laser thermal ablation of obstructing tumors leading to improved palliation in advanced cancer patients. Eight patients with recurrent head and neck tumors volunteered to enroll as part of an ongoing phase II LITT clinical trial, and also elected to be treated with systemic chemotherapy (cisplatin, 80 mg/m2) followed 24 h later by palliative laser thermal ablation. Laser treatments were repeated in patients with residual disease or recurrence for a total of 27 LITT sessions. Four of the 8 patients treated with laser thermal chemotherapy remained alive after a median follow-up of 12 months. Of the 12 tumor sites treated, complete responses were located in the oral cavity (3), oropharynx (1), hypopharynx (1), maxillary sinus (1), and median survival for these patients was 9.5 months. This initial experience with cisplatinum-based laser chemotherapy indicates both safety and therapeutic potential for palliation of advanced head and neck cancer but this must be confirmed by longer follow-up in a larger cohort of patients

Multi-Class ECG Feature Importance Rankings: Cardiologists vs. Algorithms

Cardiologists have been using electrocardiogram features to diagnose a wide variety of heart conditions for many decades. There are also numerous algorithms that rank feature importance for a particular classification task. However, different algorithms often give quite different feature rankings. Therefore, we compared the feature importance rankings obtained by various algorithms with the features that cardiologists use for diagnosis

Acute cigarette smoke-induced eQTL affects formyl peptide receptor expression and lung function

Background and objective Cigarette smoking is one of the most prevalent causes of preventable deaths worldwide, leading to chronic diseases, including chronic obstructive pulmonary disease (COPD). Cigarette smoke is known to induce significant transcriptional modifications throughout the respiratory tract. However, it is largely unknown how genetic profiles influence the smoking-related transcriptional changes and how changes in gene expression translate into altered alveolar epithelial repair responses. Methods We performed a candidate-based acute cigarette smoke-induced eQTL study, investigating the association between SNP and differential gene expression of FPR family members in bronchial epithelial cells isolated 24 h after smoking and after 48 h without smoking. The effects FPR1 on lung epithelial integrity and repair upon damage in the presence and absence of cigarette smoke were studied in CRISPR-Cas9-generated lung epithelial knockout cells. Results One significant (FDR 2-fold change in gene expression. The minor allele of rs3212855 was associated with significantly higher gene expression of FPR1, FPR2 and FPR3 upon smoking. Importantly, the minor allele of rs3212855 was also associated with lower lung function. Alveolar epithelial FPR1 knockout cells were protected against CSE-induced reduction in repair capacity upon wounding. Conclusion We identified a novel smoking-related inducible eQTL that is associated with a smoke-induced increase in the expression of FPR1, FPR2 and FPR3, and with lowered lung function. in vitro FPR1 down-regulation protects against smoke-induced reduction in lung epithelial repair

Determinants of Lung Fissure Completeness

RATIONALE: New advanced bronchoscopic treatment options for patients with severe COPD have led to increased interest for COPD phenotyping, including fissure completeness. OBJECTIVES: We investigated clinical, environmental, and genetic factors contributing to fissure completeness in patients with and without COPD. METHODS: We used data of 9926 participants of the COPDGene study who underwent chest computed tomography (CT). Fissure completeness was calculated from CT scans following quantitative CT analysis at baseline and five-year follow-up. The clinical and environmental factors sex, race, smoking, COPD, emphysema, maternal smoking during pregnancy and maternal COPD were tested for impact on fissure completeness. Genome-wide association analyses were performed separately in non-Hispanic whites and African-Americans. MEASUREMENTS AND MAIN RESULTS: African-Americans had significant higher fissure completeness than non-Hispanic whites for all three fissures (p<0.001). There was no change in fissure completeness between baseline and five-year follow-up. For all fissures, No clinically relevant differences in fissure completeness were found for other clinical or environmental factors, including COPD severity. Rs2173623, rs264866, rs2407284, rs7310342, rs4904145, rs6504172, and rs7209556 showed genome-wide significant associations with fissure completeness in non-Hispanic whites. In African-Americans, rs264866, rs4904145 and rs6504172 were identified as significant associations. Rs2173623, rs6504172, and rs7209556 lead to WNT5A and HOXB antisense RNA expression, which play an important role during embryogenesis. CONCLUSIONS: Fissure completeness is genetically determined and not dependent on age, sex, smoking status, the presence and severity of COPD including exacerbation frequency, maternal smoking during pregnancy, or maternal COPD

The mitochondrial genomes of the ciliates Euplotes minuta and Euplotes crassus

Contains fulltext : 75729.pdf (publisher's version ) (Open Access)BACKGROUND: There are thousands of very diverse ciliate species from which only a handful mitochondrial genomes have been studied so far. These genomes are rather similar because the ciliates analysed (Tetrahymena spp. and Paramecium aurelia) are closely related. Here we study the mitochondrial genomes of the hypotrichous ciliates Euplotes minuta and Euplotes crassus. These ciliates are only distantly related to Tetrahymena spp. and Paramecium aurelia, but more closely related to Nyctotherus ovalis, which possesses a hydrogenosomal (mitochondrial) genome. RESULTS: The linear mitochondrial genomes of the hypotrichous ciliates Euplotes minuta and Euplotes crassus were sequenced and compared with the mitochondrial genomes of several Tetrahymena species, Paramecium aurelia and the partially sequenced mitochondrial genome of the anaerobic ciliate Nyctotherus ovalis. This study reports new features such as long 5'gene extensions of several mitochondrial genes, extremely long cox1 and cox2 open reading frames and a large repeat in the middle of the linear mitochondrial genome. The repeat separates the open reading frames into two blocks, each having a single direction of transcription, from the repeat towards the ends of the chromosome. Although the Euplotes mitochondrial gene content is almost identical to that of Paramecium and Tetrahymena, the order of the genes is completely different. In contrast, the 33273 bp (excluding the repeat region) piece of the mitochondrial genome that has been sequenced in both Euplotes species exhibits no difference in gene order. Unexpectedly, many of the mitochondrial genes of E. minuta encoding ribosomal proteins possess N-terminal extensions that are similar to mitochondrial targeting signals. CONCLUSION: The mitochondrial genomes of the hypotrichous ciliates Euplotes minuta and Euplotes crassus are rather different from the previously studied genomes. Many genes are extended in size compared to mitochondrial genes from other sources