Automatic Diagnosis for Prostate Cancer Using Run-Length Matrix Method

Prostate cancer is the most common type of cancer and the second leading cause of cancer death among men in US1. Quantitative assessment of prostate histology provides potential automatic classification of prostate lesions and prediction of response to therapy. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. In this application, we utilize a texture analysis method based on the run-length matrix for identifying tissue abnormalities in prostate histology. A tissue sample was collected from a radical prostatectomy, H&E fixed, and assessed by a pathologist as normal tissue or prostatic carcinoma (PCa). The sample was then subsequently digitized at 50X magnification. We divided the digitized image into sub-regions of 20 X 20 pixels and classified each sub-region as normal or PCa by a texture analysis method. In the texture analysis, we computed texture features for each of the sub-regions based on the Gray-level Run-length Matrix(GL-RLM). Those features include LGRE, HGRE and RPC from the run-length matrix, mean and standard deviation of the pixel intensity. We utilized a feature selection algorithm to select a set of effective features and used a multi-layer perceptron (MLP) classifier to distinguish normal from PCa. In total, the whole histological image was divided into 42 PCa and 6280 normal regions. Three-fold cross validation results show that the proposed method achieves an average classification accuracy of 89.5% with a sensitivity and specificity of 90.48% and 89.49%, respectively

Adjacent Slice Prostate Cancer Prediction to Inform MALDI Imaging Biomarker Analysis

Prostate cancer is the second most common type of cancer among men in US [1]. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. Proteomic biomarkers can improve upon these methods. MALDI molecular spectra imaging is used to visualize protein/peptide concentrations across biopsy samples to search for biomarker candidates. Unfortunately, traditional processing methods require histopathological examination on one slice of a biopsy sample while the adjacent slice is subjected to the tissue destroying desorption and ionization processes of MALDI. The highest confidence tumor regions gained from the histopathological analysis are then mapped to the MALDI spectra data to estimate the regions for biomarker identification from the MALDI imaging. This paper describes a process to provide a significantly better estimate of the cancer tumor to be mapped onto the MALDI imaging spectra coordinates using the high confidence region to predict the true area of the tumor on the adjacent MALDI imaged slice

Observation of Majorana fermions with spin selective Andreev reflection in the vortex of topological superconductor

Majorana fermion (MF) whose antiparticle is itself has been predicted in condensed matter systems. Signatures of the MFs have been reported as zero energy modes in various systems. More definitive evidences are highly desired to verify the existence of the MF. Very recently, theory has predicted MFs to induce spin selective Andreev reflection (SSAR), a novel magnetic property which can be used to detect the MFs. Here we report the first observation of the SSAR from MFs inside vortices in Bi2Te3/NbSe2 hetero-structure, in which topological superconductivity was previously established. By using spin-polarized scanning tunneling microscopy/spectroscopy (STM/STS), we show that the zero-bias peak of the tunneling differential conductance at the vortex center is substantially higher when the tip polarization and the external magnetic field are parallel than anti-parallel to each other. Such strong spin dependence of the tunneling is absent away from the vortex center, or in a conventional superconductor. The observed spin dependent tunneling effect is a direct evidence for the SSAR from MFs, fully consistent with theoretical analyses. Our work provides definitive evidences of MFs and will stimulate the MFs research on their novel physical properties, hence a step towards their statistics and application in quantum computing.Comment: 4 figures 15 page

Cobalt doped LaSrTiO3-delta as an anode catalyst: effect of Co nanoparticle precipitation on SOFCs operating on H2S-containing hydrogen

NSERC; National Nature Science Foundation of China [51072021]; China Scholarship CouncilThis article compares the effects of Co doping on phase structures and stability of lanthanum strontium titanate (LST) anodes and electrochemical measurements in solid oxide fuel cells (SOFCs) employing H2S-containing H-2 as fuel. The Co-doped LST (LSCT) with a perovskite structure was synthesized via a solid state approach, achieving excellent phase purity and refined particle size. The catalytic activity and electrochemical performance are significantly improved by introducing Co. A maximum power density of 300 mW cm(-2) was achieved at 900 degrees C with 5000 ppm H2S-H-2 in a fuel cell having a 300 mu m thick YSZ electrolyte. Trace amounts of metallic Co nanoparticles with sizes typically no larger than 10 nm in diameter were detected on the LSCT surface after reduction in H-2 at 900 degrees C. The nano-sized Co clusters could reduce the anode polarization resistance, as well as improve the cell performance, compared with undoped LST anodes. The LSCT anode catalyst was electrochemically stable in 5000 ppm H2S-H-2 during the test time at high operating temperature. The LSCT anode catalyst also had relatively high redox stability in reversible oxidation-reduction cycles

Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD

13 páginas, 7 figurasCurrent clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)-bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non-small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs. SIGNIFICANCE: This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3270/F1.large.jpg.This study was supported by Taiwan Ministry of Science and Technology grants MOST 104-2320-B-002-044-MY3, MOST 106-2320-B-002-046-MY3, and MOST 108-2320-B-002-024-MY3, National Health Research Institutes grants NHRI-EX106-10401BI and NHRI-EX109-10725BI, National Taiwan University grants NTU107L890504 and NTU110L893503 to M.-S. Lee, and National Taiwan University Hospital grants 106-003451, 107-003849, 108-004269, and 109-004720 to C.-C. Ho. This work was also supported by MINECO grants BFU2016-80570-R and RTI2018-098084-B-I00 (AEI/FEDER, UE). The authors would like to thank the Laboratory Animal Core Facility at the College of Medicine, National Taiwan University for their servicesPeer reviewe

Dramatic Co-Activation of WWOX/WOX1 with CREB and NF-κB in Delayed Loss of Small Dorsal Root Ganglion Neurons upon Sciatic Nerve Transection in Rats

BACKGROUND:Tumor suppressor WOX1 (also named WWOX or FOR) is known to participate in neuronal apoptosis in vivo. Here, we investigated the functional role of WOX1 and transcription factors in the delayed loss of axotomized neurons in dorsal root ganglia (DRG) in rats. METHODOLOGY/PRINCIPAL FINDINGS:Sciatic nerve transection in rats rapidly induced JNK1 activation and upregulation of mRNA and protein expression of WOX1 in the injured DRG neurons in 30 min. Accumulation of p-WOX1, p-JNK1, p-CREB, p-c-Jun, NF-kappaB and ATF3 in the nuclei of injured neurons took place within hours or the first week of injury. At the second month, dramatic nuclear accumulation of WOX1 with CREB (>65% neurons) and NF-kappaB (40-65%) occurred essentially in small DRG neurons, followed by apoptosis at later months. WOX1 physically interacted with CREB most strongly in the nuclei as determined by FRET analysis. Immunoelectron microscopy revealed the complex formation of p-WOX1 with p-CREB and p-c-Jun in vivo. WOX1 blocked the prosurvival CREB-, CRE-, and AP-1-mediated promoter activation in vitro. In contrast, WOX1 enhanced promoter activation governed by c-Jun, Elk-1 and NF-kappaB. WOX1 directly activated NF-kappaB-regulated promoter via its WW domains. Smad4 and p53 were not involved in the delayed loss of small DRG neurons. CONCLUSIONS/SIGNIFICANCE:Rapid activation of JNK1 and WOX1 during the acute phase of injury is critical in determining neuronal survival or death, as both proteins functionally antagonize. In the chronic phase, concurrent activation of WOX1, CREB, and NF-kappaB occurs in small neurons just prior to apoptosis. Likely in vivo interactions are: 1) WOX1 inhibits the neuroprotective CREB, which leads to eventual neuronal death, and 2) WOX1 enhances NF-kappaB promoter activation (which turns to be proapoptotic). Evidently, WOX1 is the potential target for drug intervention in mitigating symptoms associated with neuronal injury

Projectile Velocity and Crater Formation in Water

The relationship between the velocity of impact and maximum crater diameter was found for two steel balls dropped into water using 300 fps video. The maximum diameter of the crater was found to be proportional to the impact velocity and independent of the diameter of the ball