Protective effects of urocortin 2 against caerulein-induced acute pancreatitis.

Because little is known about the role of corticotropin-releasing factor (CRF) agonists in regulating responses in pancreatitis, we evaluated the effects of urocortin 2 (UCN2) and stressin1 in caerulein-induced acute pancreatitis (AP) model in rats. Male rats were pretreated with UCN2 or stressin1 for 30 min followed by induction of AP with supraphysiologic doses of caerulein. Serum amylase and lipase activity, pancreatic tissue necrosis, immune cell infiltrate, nuclear factor (NF)-κB activity, trypsin levels, and intracellular Ca2+ ([Ca2+]i) were ascertained. UCN2, but not stressin1 attenuated the severity of AP in rats. UCN2, but not stressin1, reduced serum amylase and lipase activity, cell necrosis and inflammatory cell infiltration in AP. NF-κB activity in pancreatic nuclear extracts increased in AP and UCN2 treatment reduced caerulein-induced increases in NF-κB activity by 42%. UCN2 treatment prevented caerulein-induced degradation of IκB-α in the cytosolic fraction as well as increased levels of p65 subunit of NF-κB in the cytosolic fraction. Pancreatic UCN2 levels decreased in AP compared with saline. UCN2 evoked [Ca2+]i responses in primary acinar cells and abolished caerulein-evoked [Ca2+]i responses at 0.1nM, and decreased by ~50% at 1.0nM caerulein. UCN2 stimulation resulted in redistribution of a portion of F-actin from the apical to the basolateral pole. UCN2 prevented the massive redistribution of F-actin observed with supraphysiologic doses of caerulein. UCN2, but not stressin1 attenuated severity of an experimental pancreatitis model. The protective effects of UCN2, including anti-inflammatory and anti-necrotic effects involve activation of the CRF2 receptor, [Ca2+]i signaling, and inhibition of NF-κB activity

Essential Role of Lyn in Fibrosis.

Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we identify the hyperactive Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and is increased ~11-fold in chronic pancreatitis compared to normal tissue. Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of migration and proliferation of human chronic pancreatitis myofibroblasts in vitro, while leaving migration and proliferation of normal myofibroblasts only slightly affected. Furthermore, inhibition of Lyn prevents synthesis of procollagen and collagen in myofibroblasts in a mouse model of chronic pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of myofibroblast migration, proliferation, and collagen production, is a key target for preventing fibrosis

A Machine Learning Approach for Detection of Phished Websites Using Neural Networks

Phishing is a means of obtaining confidential information through fraudulent website that appear to be legitimate .On detection of all the criteria ambiguities and certain considerations involve hence neural network techniques are used to build an effective tool in identifying phished websites There are many phishing detection techniques available, but a central problem is that web browsers rely on a black list of known phishing website, but some phishing website has a lifespan as short as a few hours. These website with a shorter lifespan are known as zero day phishing website. Thus, a faster recognition system needs to be developed for the web browser to identify zero day phishing website. To develop a faster recognition system, a neural network technique is used which reduces the error and increases the performance. This paper describes a framework to better classify and predict the phishing sites

A Further Study of Linux Kernel Hugepages on A64FX with FLASH, an Astrophysical Simulation Code

We present an expanded study of the performance of FLASH when using Linux Kernel Hugepages on Ookami, an HPE Apollo 80 A64FX platform. FLASH is a multi-scale, multi-physics simulation code written principally in modern Fortran and makes use of the PARAMESH library to manage a block-structured adaptive mesh. Our initial study used only the Fujitsu compiler to utilize standard hugepages (hp), but further investigation allowed us to utilize hp for multiple compilers by linking to the Fujitsu library libmpg and transparent hugepages (thp) by enabling it at the node level. By comparing the results of hardware counters and in-code timers, we found that hp and thp do not significantly impact the runtime performance of FLASH. Interestingly, there is a significant reduction in the TLB misses, differences in cache and memory access counters, and strange behavior is observed when using thp.Comment: 10 pages, 2 figures, 7 tables. Proceedings for Practice and Experience in Advanced Research Computing (PEARC '23), July 23--27, 2023, Portland, OR, US

Ookami: An A64FX Computing Resource

We present a look at Ookami, a project providing community access to a testbed supercomputer with the ARM-based A64FX processors developed by a collaboration between RIKEN and Fujitsu and deployed in the Japanese supercomputer Fugaku. We provide an overview of the project and details of the hardware, and describe the user base and education/training program. We present highlights from previous performance studies of two astrophysical simulation codes and present a strong scaling study of a full 3D supernova simulation as an example of the the machine’s capability

Using mass spectrometry imaging to map fluxes quantitatively in the tumor ecosystem

Tumors are comprised of a multitude of cell types spanning different microenvironments. Mass spectrometry imaging (MSI) has the potential to identify metabolic patterns within the tumor ecosystem and surrounding tissues, but conventional workflows have not yet fully integrated the breadth of experimental techniques in metabolomics. Here, we combine MSI, stable isotope labeling, and a spatial variant of Isotopologue Spectral Analysis to map distributions of metabolite abundances, nutrient contributions, and metabolic turnover fluxes across the brains of mice harboring GL261 glioma, a widely used model for glioblastoma. When integrated with MSI, the combination of ion mobility, desorption electrospray ionization, and matrix assisted laser desorption ionization reveals alterations in multiple anabolic pathways. De novo fatty acid synthesis flux is increased by approximately 3-fold in glioma relative to surrounding healthy tissue. Fatty acid elongation flux is elevated even higher at 8-fold relative to surrounding healthy tissue and highlights the importance of elongase activity in glioma

Studies on Old World Bluestems III

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