USE-Net: Incorporating Squeeze-and-Excitation blocks into U-Net for prostate zonal segmentation of multi-institutional MRI datasets

Prostate cancer is the most common malignant tumors in men but prostate Magnetic Resonance Imaging (MRI) analysis remains challenging. Besides whole prostate gland segmentation, the capability to differentiate between the blurry boundary of the Central Gland (CG) and Peripheral Zone (PZ) can lead to differential diagnosis, since tumor's frequency and severity differ in these regions. To tackle the prostate zonal segmentation task, we propose a novel Convolutional Neural Network (CNN), called USE-Net, which incorporates Squeeze-and-Excitation (SE) blocks into U-Net. Especially, the SE blocks are added after every Encoder (Enc USE-Net) or Encoder-Decoder block (Enc-Dec USE-Net). This study evaluates the generalization ability of CNN-based architectures on three T2-weighted MRI datasets, each one consisting of a different number of patients and heterogeneous image characteristics, collected by different institutions. The following mixed scheme is used for training/testing: (i) training on either each individual dataset or multiple prostate MRI datasets and (ii) testing on all three datasets with all possible training/testing combinations. USE-Net is compared against three state-of-the-art CNN-based architectures (i.e., U-Net, pix2pix, and Mixed-Scale Dense Network), along with a semi-automatic continuous max-flow model. The results show that training on the union of the datasets generally outperforms training on each dataset separately, allowing for both intra-/cross-dataset generalization. Enc USE-Net shows good overall generalization under any training condition, while Enc-Dec USE-Net remarkably outperforms the other methods when trained on all datasets. These findings reveal that the SE blocks' adaptive feature recalibration provides excellent cross-dataset generalization when testing is performed on samples of the datasets used during training.Comment: 44 pages, 6 figures, Accepted to Neurocomputing, Co-first authors: Leonardo Rundo and Changhee Ha

Critical Transition in Tissue Homeostasis Accompanies Murine Lung Senescence

BACKGROUND: Respiratory dysfunction is a major contributor to morbidity and mortality in aged populations. The susceptibility to pulmonary insults is attributed to "low pulmonary reserve", ostensibly reflecting a combination of age-related musculoskeletal, immunologic and intrinsic pulmonary dysfunction. METHODS/PRINCIPAL FINDINGS: Using a murine model of the aging lung, senescent DBA/2 mice, we correlated a longitudinal survey of airspace size and injury measures with a transcriptome from the aging lung at 2, 4, 8, 12, 16 and 20 months of age. Morphometric analysis demonstrated a nonlinear pattern of airspace caliber enlargement with a critical transition occurring between 8 and 12 months of age marked by an initial increase in oxidative stress, cell death and elastase activation which is soon followed by inflammatory cell infiltration, immune complex deposition and the onset of airspace enlargement. The temporally correlative transcriptome showed exuberant induction of immunoglobulin genes coincident with airspace enlargement. Immunohistochemistry, ELISA analysis and flow cytometry demonstrated increased immunoglobulin deposition in the lung associated with a contemporaneous increase in activated B-cells expressing high levels of TLR4 (toll receptor 4) and CD86 and macrophages during midlife. These midlife changes culminate in progressive airspace enlargement during late life stages. CONCLUSION/SIGNIFICANCE: Our findings establish that a tissue-specific aging program is evident during a presenescent interval which involves early oxidative stress, cell death and elastase activation, followed by B lymphocyte and macrophage expansion/activation. This sequence heralds the progression to overt airspace enlargement in the aged lung. These signature events, during middle age, indicate that early stages of the aging immune system may have important correlates in the maintenance of tissue morphology. We further show that time-course analyses of aging models, when informed by structural surveys, can reveal nonintuitive signatures of organ-specific aging pathology

Ablations of Ghrelin and Ghrelin Receptor Exhibit Differential Metabolic Phenotypes and Thermogenic Capacity during Aging

mice are adaptive. mice.Our data therefore suggest that GHS-R ablation activates adaptive thermogenic function(s) in BAT and increases EE, thereby enabling the retention of a lean phenotype. This is the first direct evidence that the ghrelin signaling pathway regulates fat-burning BAT to affect energy balance during aging. This regulation is likely mediated through an as-yet-unidentified new ligand of GHS-R

Optical dating of river terrace sediments from Kanto plains, Japan

Optical dating of river terrace sediments has been carried out in a test of the methodology for luminescence age determination of river terrace formation over the last 100 ka. In this study, samples were collected at river terraces, whose ages were estimated by marker tephra geochronology and from a recent riverbed in the Kanto Plain, Japan. Samples from the recent riverbed show a weak OSL signal only and gave young ages. Samples of river terrace sediments for optical dating were collected systematically from the section of about 8 m at the wall of a gravel quarry. The optical ages found corresponded well with those estimated by the age of the marker tephras for samples deeper than 2.5 m. However, the samples from the ground surface to 2.5 m exhibited considerable scatter in the growth curves and gave a wide range of ages, all significantly exceeding expectation. This was attributed to the mixing of different age sediments by inundation and/or human activities. Analyses of OSL from single grains of quartz confirmed that these sediments were composed of grains having a wide range of palaeodoses, consistent with such mixing

Ingratiation as an adapting strategy: Its relationship with career adaptability, career sponsorship, and promotability

Guided by the Career Construction Theory (Savickas, 2013), our research model posits that individuals rely on their adaptability resources and implement adapting responses, in the form of ingratiation, to increase their promotability at work. In addition, the indirect relationship between career adaptability and promotability via ingratiation is further strengthened by high career sponsorship. The research model was tested and the translated Career Adapt-Abilities Scale (CAAS) Thailand form was validated using a cross-sectional survey of 265 subordinate–supervisor dyads. Results demonstrate adequate levels of internal consistency (ɑ = .96) and the factor structure corresponded with prior CAAS international validation. The moderated mediation model was supported and as expected: (a) ingratiation, as an adapting response, mediated the positive relationship between career adaptability and promotability, and (b) the mediated relationship between career adaptability and promotability via ingratiation was stronger for individuals with higher career sponsorship. Taken together, the findings support the cross-national measurement equivalence and utility of CAAS in non-Western and developing countries. More importantly, our study offers the groundwork for understanding adapting responses and the augmenting role of career-specific contextual support

The role of self-monitoring and academic effort in students’ career adaptability and job search self-efficacy

This article examines the relationship between career adaptability, self-monitoring, academic effort, and job search self-efficacy among university students. Guided by the career construction and self-monitoring theories, we propose that self-monitoring mediates the relationship between career adaptability and job search self-efficacy. Furthermore, we hypothesize that the indirect relationship is stronger for those with high academic effort. We test our proposed model using two samples (Sample 1 = 340, Sample 2 = 547) of university students from Thailand. Results confirm our hypothesized relationships and suggest that career adaptability is positively associated with job search self-efficacy above and beyond the effects of gender. Moderated mediation analyses revealed that the conditional indirect effect of career adaptability in predicting job search self-efficacy via self-monitoring is stronger for students with high as opposed to low levels of academic effort. Implications for theory and practice are discussed

Mannose- and Mannobiose-Specific Responses of the Insect-Associated Cellulolytic Bacterium Streptomyces sp. Strain SirexAA-E

The cellulolytic insect symbiont bacterium Streptomyces sp. strain SirexAA-E secretes a suite of carbohydrate-active enzymes (CAZymes), which are involved in the degradation of various polysaccharides in the plant cell wall, in response to the available carbon sources. Here, we examined a poorly understood response of this bacterium to mannan, one of the major plant cell wall components. SirexAA-E grew well on mannose, carboxymethyl cellulose (CMC), and locust bean gum (LBG) as sole carbon sources in the culture medium. The secreted proteins from each culture supematant were tested for their polysaccharide-degrading ability, and the composition of secreted CAZymes in each sample was determined by liquid chromatography-tandem mass spectrometry (LC-MS/ MS). The results indicated that mannose, LBG, and CMC induced the secretion of mannan and cellulose-degrading enzymes. Interestingly, two alpha-1,2-mannosidases were abundantly secreted during growth on mannose and LBG. Using genomic analysis, we found a unique 12-bp palindromic sequence motif at 4 locations in the SirexAA-E genome, two of which were found upstream of the above-mentioned alpha-1,2-mannosidase genes, along with a newly identified mannose and mannobiose-responsive transcriptional regulator, SsManR. Furthermore, the previously reported cellobiose-responsive repressor, SsCebR, was determined to also use mannobiose as an effector ligand. To test whether mannobiose induces the sets of genes under the control of the two regulators, SirexAA-E was grown on mannobiose, and the secretome composition was analyzed. As hypothesized, the composition of the mannobiose secretome combined sets of CAZymes found in both LBG and CMC secretomes, and thus they are likely under the regulation of both SsManR and SsCebR. IMPORTANCE Streptomyces sp. SirexAA-E, a microbial symbiont of biomass-harvesting insects, secretes a suite of polysaccharide-degrading enzymes dependent on the available carbon sources. However, the response of this bacterium to mannan has not been documented. In this study, we investigated the response of this bacterium to mannose, mannobiose, and galactomannan (LBG). By combining biochemical, proteomic, and genomic approaches, we discovered a novel mannose and mannobiose responsive transcriptional regulator, SsManR, which selectively regulates three alpha-1,2-mannosidasecoding genes. We also demonstrated that the previously described cellobiose responsive regulator, SsCebR, could use mannobiose as an effector ligand. Overall, our findings suggest that the Streptomyces sp. SirexAA-E responds to mannose and mannooligosaccharides through two different transcriptional repressors that regulate the secretion of the plant cell wall-degrading enzymes to extract carbon sources in the host environment