gebhart/patrepeval huggingface dataset:
Select EZH2 inhibitors enhance the viral mimicry effects of DNMT inhibition through a mechanism involving calcium-calcineurin-NFAT signaling (2023)

Abstract DNA methyltransferase (DNMT) inhibitors are FDA-approved for various hematological malignancies but have limited efficacy in solid tumors. DNA hypomethylation with these drugs is associated with elevated lysine 27 tri-methylation on histone H3 (H3K27me3). We hypothesized that this EZH2-dependent repressive mark limits the full potential of DNMT inhibition. Here, we show in cell line and tumoroid models of colorectal cancer, that low-dose DNMT inhibition sensitizes cells to selective EZH2 inhibitors that have limited single agent toxicity, and that EZH2 inhibition enhances DNMT inhibitor-driven molecular and therapeutic effects. Through integrative epigenomic analyses, we reveal that DNMT inhibition induces H3K27me3 accumulation at genomic regions poised with EZH2. Unexpectedly, combined treatment alters the epigenome landscape to promote transcriptional upregulation of the calcium-calcineurin-NFAT signaling pathway. Blocking this pathway limits the transcriptional activating effects of the drug combination, including expression of transposable elements and innate immune response genes within a viral defense pathway. Consistently, we demonstrate positive correlations between DNMT inhibitor- and innate immune response-associated transcription profiles and calcium signal activation in primary human colon cancer specimens. Collectively, our study demonstrates that compensatory EZH2 activity following DNA hypomethylation presents a barrier to the therapeutic action of DNMT inhibition in colon cancer, reveals a new application of EZH2 inhibitors beyond cancers associated with PRC2 hyperactivity, and links calcium-calcineurin-NFAT signaling to epigenetic therapy-induced viral mimicry. Highlights Select EZH2 inhibitors enhance the transcriptional activating and antiproliferative effects of DNA hypomethylating agents in colon cancer cells. The mechanism involves blockade of H3K27me3 accumulation in regions of the genome poised for PRC2 activity. DNMT inhibitor + EZH2 inhibitor treatment transcriptionally upregulates calcium-calcineurin- NFAT signaling, and this pathway is necessary for complete induction of viral mimicry and innate immune response pathways. The therapeutic utility of EZH2 inhibitors may be extended beyond cancers with PRC2 hyperactivity in combination regimens with DNMT inhibitors.
Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors (1990)

The synthesis and biochemical evaluation of novel 1,2,4-oxadiazole-based muscarinic agonists which can readily penetrate into the CNS is reported. Efficacy and binding of these compounds are markedly influenced by the structure and physicochemical properties of the cationic head group. In a series of azabicyclic ligands efficacy and affinity are influenced by the size of the surface area presented to the receptor, at the active site, and the degree of conformational flexibility. The exo-1-azanorbornane 16a represents the optimum arrangement, and this compound is one of the most efficacious and potent muscarinic agonists known. In a series of isoquinuclidine based muscarinic agonists efficacy and affinity are influenced by the geometry between the cationic head.group and hydrogen bond acceptor pharmacophore and steric bulk in the vicinity of the base. The anti configuration represented by 22a is optimal for muscarinic activity. Ligands with pKa below 6.5 show poor binding to the muscarinic receptor as exemplified by the diazabicyclic derivative 42.
Preparation and EPR Characteristics of $ZnGa_2O_4$ : Mn Phosphor (1998)

ZnGa2O4: Mn phosphors were prepared by a new chemical process, and their photoluminescence and electron paramagnetic resonance characteristics were investigated. The chemical method showed a low temperature formation of phosphors and a rod-type shape of particles. The strong ultraviolet emission was observed in the undoped ZnGa2O4 phosphor, while strong green emission in the Mn2+-activated ZnGa2O4 phosphor. The green emission intensity of the phosphor prepared by the chemical method was much stronger than that prepared by the conventional method. This difference with preparation methods was interpreted as due to the difference in the distribution of Mn2+ in the host lattice. From EPR results, it was explained that the line intensity of the undoped ZnGa2O4 is associated with the electrical conductivity of this material and the concentration quenching of green luminescence of ZnGa2O4: Mn at higher Mn2+ concentration is attributed to the coupling by exchange interaction between Mn2+ ions.
An Analysis of Published Informal Reading Inventories (1982)

Believing that IRIs have genuine value in a comprehensive diagnostic program if used properly, we decided it would be useful to examine a number of the commercially prepared IRIs currently available for the purpose of comparing them and describing their unique features for teachers.
Extracellular synthesis of zinc oxide nanoparticle using seaweeds of gulf of Mannar, India (2013)

Based on the FTIR results, fucoidan water soluble pigments present in S. myriocystum leaf extract is responsible for reduction and stabilization of zinc oxide nanoparticles. by this approach are quite stable and no visible changes were observed even after 6 months. These soluble elements could have acted as both reduction and stabilizing agents preventing the aggregation of nanoparticles in solution, extracellular biological synthesis of zinc oxide nanoparticles of size 36 nm.
Imaging Optical interferometry (1991)

Abstract Interferometry at optical wavelengths is very similar to radio interferometry, once the fundamental differences in detectors are accounted for. The Mount Wilson Mark III optical interferometer has been used for optical interferometry of stars and stellar systems. Success with the Mark III has lead to the current program at the Naval Research Laboratory to build the Big Optical Array (BOA), which will be an imaging interferometer. Imaging simulations show that BOA will be able to produce images of complex stellar systems, with a resolution as fine as 0.2 milliarcseconds.
Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4 (1994)

The present study was undertaken to determine whether there is selective tissue distribution of vitamin K in the rat and whether this distribution mirrors the distribution of tissue vitamin K metabolism. The effects of feeding a vitamin K-free diet followed by resupplementation with phylloquinone (K1) were studied. K1 was recovered in all tissues. In K1-supplemented rats, most tissues accumulated K1 relative to plasma K1 with the highest levels in liver, heart, bone, and cartilaginous tissue (sternum). Low K1 levels were found in the brain. In the K1-free rats, relatively high K1 levels were still found in heart, pancreas, bone and sternum. Surprisingly, menaquinone-4 (MK-4) was detected in all tissues, with low levels in plasma and liver, and much higher levels in pancreas, salivary gland and sternum. MK-4 levels exceeded K1 levels in brain, pancreas, salivary gland and sternum. Supplementation with K1, orally and by intravenous infusion, caused MK-4 levels to rise. Some accumulation of K1 and MK-4 in the mitochondrial fraction was found for kidney, pancreas and salivary gland. In the liver the higher menaquinones (MK-6-9) accumulated in the mitochondria. The results indicate that: (1) there is selective tissue distribution of K1 and MK-4, (2) dietary K1 is a source of MK-4. The results also suggest there may be an as yet unrecognized physiological function for vitamin K (MK-4).
On the development of a high-resolution multi-pinhole SPECT/CT (2005)

Multi-Pinhole SPECT systems provide high-resolution and high-sensitivity imaging for small animal research. We currently perform SPECT imaging using commercial gamma cameras upgraded with multi-pinhole collimators. We have shown that for most tasks we are capable of achieving reconstructed spatial resolutions as low as 1.2 mm with average sensitivities up to 1600 cps/MBq. In an attempt to achieve better orientation in SPECT images we are equipping a compact commercial gamma camera with an X-ray CT system to create an integrated dual modality system. We are adding the CT system to our gantry to enhance the imaging capabilities of our SPECT system. Our gantry is equipped with a 3D translation stage that enables us to image objects that extend beyond the field of view in the axial direction by performing helical scan orbits. We are capable of performing such helical scan orbits for both modalities. We have designed a cost-effective CT add-on that provides additional anatomical information to the systems users. Specifically, the CT reconstructions aid in the acquisition and interpretation of the corresponding SPECT images.
NIMG-08. A MULTI-CENTER RADIOMICS-BASED MODEL TO DIFFERENTIATE BETWEEN NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PLEXIFORM NEUROFIBROMAS AND MALIGNANT PERIPHERAL NERVE SHEATH TUMORS (2021)

Abstract BACKGROUND Several MRI features are proposed to distinguish between plexiform neurofibromas (PNF) and malignant peripheral nerve sheath tumors (MPNST) in neurofibromatosis type 1 (NF1), including tumor size, margins, and degree of heterogeneity. However, most of these features are descriptive in nature, subject to intra-/interrater variability, and based on small single-institution studies. The goal of this study was to identify radiomic features that can differentiate between NF1-associated PNF and MPNST. METHODS 31 MPNSTs and 24 PNFs from five centers were segmented on short TI inversion recovery sequences using a semi-automated segmentation software (3DQI). Standard pre-processing was performed, including N4 bias field correction, intensity normalization (using a mean of 120 SI and standard deviation of 80 SI), and resampling to 1 mm3 voxel resolution. 1688 radiomic features were extracted from the tumor region of interest using PyRadiomics, an open-source Python radiomics package. To classify tumors as PNF or MPNST, we implemented the Boruta algorithm and correlation removal for selection of important features. A Random Forest model was built using the top ten selected features. Five-fold cross-validation was performed and repeated 100 times. Model performance was evaluated using the area under the ROC curve (AUC), sensitivity, specificity, accuracy, and confidence intervals. RESULTS The top ten features included in the model were five intensity features, two shape features, and three texture features. The model demonstrated an AUC of 0.891 (95% CI 0.882-0.899), sensitivity of 0.744, specificity of 0.847, and accuracy of 0.802 (95% CI 0.792-0.813). CONCLUSIONS Our machine learning model demonstrated high performance in classifying tumors as either PNF or MPNST in NF1 individuals. Inclusion of additional tumors for model training and testing on an independent dataset are underway. Ultimately, our model may enable improved differentiation between PNF and MPNST compared to descriptive MRI features, permit early patient risk stratification, and improve patient outcomes.
Popcorn Inspired Porous Macrocellular Carbon: Rapid Puffing Fabrication from Rice and Its Applications in Lithium–Sulfur Batteries (2017)

Abstract The advancement of electrochemical energy storage is closely bound up with the breakthrough of controllable fabrication of energy materials. Inspired by a popcorn fabrication from corn raw, herein a unique porous macrocellular carbon composed of cross‐linked nano/microsheets by a powerful puffing of rice precursor is described. The rice is directly puffed with a volume enlargement of ≈20 times when it is instantaneously released from a sealed environment with a high pressure of 1.0 MPa at 200 °C. Interestingly, when metal (e.g., Ni) nanoparticles are embedded in the puffed rice derived carbon (PRC), high‐quality PRC/metal composites are achieved with attractive properties of a high electrical conductivity of ≈7.2 × 10 4 S m −1 , a large porosity of 85.1%, and a surface area of 1492.2 m 2 g −1 . The PRC/Ni are employed as a host in lithium–sulfur batteries. The designed PRC/Ni/S electrode exhibits a high reversible capacity of 1257.2 mA h g −1 at 0.2 C, a prolonged cycle life (821 mA h g −1 after 500 cycles), and enhanced rate capability, much better than other counterparts (PRC/S and rGO/S). The excellent properties are attributed to the advantages of PRC/Ni network with a high electrical conductivity, strong adsorption/blocking ability for polysulfides, and interconnected porous framework.
Pathogenicity and Transmission in Pigs of the Novel A(H3N2)v Influenza Virus Isolated from Humans and Characterization of Swine H3N2 Viruses Isolated in 2010-2011 (2012)

Swine influenza virus (SIV) H3N2 with triple reassorted internal genes (TRIG) has been enzootic in Unites States since 1998. Transmission of the 2009 pandemic H1N1 (pH1N1) virus to pigs in the United States was followed by reassortment with endemic SIV, resulting in reassorted viruses that include novel H3N2 genotypes (rH3N2p). Between July and December 2011, 12 cases of human infections with swine-lineage H3N2 viruses containing the pandemic matrix (pM) gene [A(H3N2)v] were detected. Whole-genome analysis of H3N2 viruses isolated from pigs from 2009 to 2011 sequenced in this study and other available H3N2 sequences showed six different rH3N2p genotypes present in the U.S. swine population since 2009. The presence of the pM gene was a common feature among all rH3N2p genotypes, but no specific genotype appeared to predominate in the swine population. We compared the pathogenic, transmission, genetic, and antigenic properties of a human A(H3N2)v isolate and two swine H3N2 isolates, H3N2-TRIG and rH3N2p. Our in vivo study detected no increased virulence in A(H3N2)v or rH3N2p viruses compared to endemic H3N2-TRIG virus. Antibodies to cluster IV H3N2-TRIG and rH3N2p viruses had reduced cross-reactivity to A(H3N2)v compared to other cluster IV H3N2-TRIG and rH3N2p viruses. Genetic analysis of the hemagglutinin gene indicated that although rH3N2p and A(H3N2)v are related to cluster IV of H3N2-TRIG, some recent rH3N2p isolates appeared to be forming a separate cluster along with the human isolates of A(H3N2)v. Continued monitoring of these H3N2 viruses is necessary to evaluate the evolution and potential loss of population immunity in swine and humans.
Control of morphology in synthesizing mesoporous silica (2000)

Abstract Mesoporous silica can be synthesized by either the alkaline route or the acidic route, both using surfactants as templates. Morphological transformations of mesoporous silica can produce various hierarchical orders. Different morphologies are produced under different synthetic conditions. In the alkaline route, the surfactant/silicate liquid crystal system undergoes phase transformation to form vesicles and further transforms to the hexagonal phase. The results are tubule-within-tubule and hollow pillar-within-sphere structures depending on cosurfactant/surfactant composition. Using nitric acid in the acidic route, one can obtain hierarchical ropes or gyroids depending on stirring conditions. Ammonia hydrothermal treatment can induce further morphological transformation to nanotubes of mesoporous silica.
Dependence of the grain boundary potential barrier height of BaTiO3ceramics on donor dopant concentration (1990)

Barium titanate ceramics exhibiting the positive temperature coefficient of resistance (PTCR) effect were prepared with donor concentrations ranging from 0.05-1.8 at.%. The resistance of the various samples (normalised to give the specific resistance of a unit area of grain boundary rho L in order to eliminate the effect of the observed reduction in grain size with increased donor concentration) was measured in the vicinity of the ferroelectric transition temperature Tc. Arrhenius plots of rho L against (T- theta )/T, where T is the absolute temperature and theta is the Curie point, were then obtained for T>Tc. The plots were found to be linear up to a few degrees below the temperature corresponding to the maximum value of rho L, in agreement with the well known Heywang model. The potential barrier heights, calculated from the slopes of the Arrhenius plots, were found to be similar for samples containing 0.1-1.4 at.% ( approximately 0.2 eV at 150 degrees C) and greater in more heavily doped specimens (0.4 eV at the same temperature). However, the Arrhenius plots belonging to samples containing 0.05 at.% were linear for a small temperature range since the PTCR jump was very small and consequently it was not possible to calculate the potential barrier height with any accuracy.
Design Space Exploration for Softmax Implementations (2020)

Deep Neural Networks (DNN) are crucial components of machine learning in the big data era. Significant effort has been put into the hardware acceleration of convolution and fully-connected layers of neural networks, while not too much attention has been put on the Softmax layer. Softmax is used in terminal classification layers in networks like ResNet, and is also used in intermediate layers in networks like the Transformer. As the speed for other DNN layers keeps improving, efficient and flexible designs for Softmax are required. With the existence of several ways to implement Softmax in hardware, we evaluate various softmax hardware designs and the trade-offs between them. In order to make the design space exploration more efficient, we also develop a parameterized generator which can produce softmax designs by varying multiple aspects of a base architecture. The aspects or knobs are parallelism, accuracy, storage and precision. The goal of the generator is to enable evaluation of tradeoffs between area, delay, power and accuracy in the architecture of a softmax unit. We simulate and synthesize the generated designs and present results comparing them with the existing state-of-the-art. Our exploration reveals that the design with parallelism of 16 can provide the best area-delay product among designs with parallelism ranging from 1 to 32. It is also observed that look-up table based approximate LOG and EXP units can be used to yield almost the same accuracy as the full LOG and EXP units, while providing area and energy benefits. Additionally, providing local registers for intermediate values is seen to provide energy savings.
Phosphodiesterase as a New Therapeutic Target for the Treatment of Spinal Cord Injury and Neurodegenerative Diseases (2014)

Interest in Central Nervous System (CNS) inflammation has rapidly grown over the past decade driven by the increasing evidence indicating that chronic inflammation and neuroinflammation in the brain may play an important role in the progressive neuronal cell death in many chronic CNS diseases, such as Alzheimer and Parkinson's diseases, traumatic brain injury, spinal cord injury (SCI), as well as pathologies associated with CNS infections. In peripheral tissues, generally inflammation has a protective role limiting the survival and proliferation of invading pathogens, promoting tissue repair and recovery. This innate response normally resolves over a few weeks, accompanyied by tissue repair aided by macrophages recruited to the site. However, when the inflammatory response does not undergo resolution, it might turn into chronic inflammation. Any chronic inflammatory process can damage healthy tissue and the brain may be particularly vulnerable, since destroyed neurons can not be replaced. Recently, several reports have suggested that phosphodiesterases (PDEs) are new targets for central nervous system (CNS) diseases. All the PDEs are expressed in the CNS, making this gene family a particularly attractive source of new targets for the treatment of psychiatric and neurodegenerative disorders. Significantly, all neurons express multiple PDEs, which differ in cyclic nucleotide specificity, affinity, regulatory control and subcellular compartmentalization. Therefore, PDEs inhibition represents a mechanism through which it could be possible to precisely modulate neuronal activity. In this article, we review the current state of art of PDEs in the CNS diseases associated with neuroinflammation.
In Situ Structural Characterization of a Recombinant Protein in Native Escherichia coli Membranes with Solid-State Magic-Angle-Spinning NMR (2020)

The feasibility of using solid-state MAS NMR for in situ structural characterization of the LR11 (sorLA) transmembrane domain in native Escherichia coli (E. coli) membranes is presented. LR11 interacts with the human amyloid precursor protein (APP), a central player in the pathology of Alzheimer's disease. The background signals from E. coli lipids and membrane proteins had only minor effects on LR11 TM resonances. Approximately 50% of the LR11 TM residues were assigned by using 13C PARIS data. These assignments allow comparisons of the secondary structure of LR11 TM in native membrane environments and in commonly used membrane mimics (e.g. micelles). In situ spectroscopy bypasses several obstacles in the preparation of membrane proteins for structural analysis, and offers an opportunity to investigate the consequences of membrane heterogeneity, bilayer asymmetry, chemical gradients, and macromolecular crowding on the protein structure.
Protein kinase B/Akt activates c-Jun NH2-terminal kinase by increasing NO production in response to shear stress (2001)

Laminar shear stress activates c-Jun NH(2)-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (Akt(AA)) and a constitutively active mutant (Akt(Myr)) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of Akt(AA) in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of Akt(Myr) by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O(2-), which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.
Improved solid phase synthesis of apamin, the principal neurotoxin of bee venom : structure-function studies based on synthetic analogues (1978)

Improved solid phase synthesis of apamin, the principal neurotoxin of bee venom : structure-function studies based on synthetic analogues
Effect of annealing on the optical properties of HfO2 (2010)

Post-annealing of HfO2 thin films is found to affect the absorption loss at 1 µm, and the subpicosecond laser-induced breakdown behavior. These effects are attributed to modifications of the density of intrinsic defects and photo-induced defects, respectively.