gebhart/patrepeval huggingface dataset:
Modulating AML1-ETO with Signature-Based Small Molecule Library Screening. (2006)

Abstract We sought to develop a strategy to pharmacologically modulate AML1-ETO, the most common gene rearrangement associated with acute myeloblastic leukemia (AML). Like many other oncogenic transcription factors associated with the acute leukemias, AML1-ETO has been considered undruggable. In principle, these well-characterized somatic mutations identified in the acute leukemias represent unique, tumor-specific therapeutic targets. In practice, acute leukemia therapy continues to focus on nonspecific cytotoxic agents. In order to address this challenge, we developed a genomic, signature-based small molecule library screening approach, Gene Expression-based High-throughput Screening (GE-HTS). This approach uses gene expression signatures as surrogates for different biological states in a small molecule library screen. We focused our initial efforts on identifying modulators of AML1-ETO. First, a 25-gene signature for AML1-ETO abrogation was defined by transcriptional profiling of t(8;21) Kasumi-1 cells with and without AML1-ETO-directed RNA interference and with a U937 inducible model of AML1-ETO. The signature was confirmed in microarray data from t(8;21)-containing primary patient leukemias (p &lt; 0.001). Next, the ability of 2,600 FDA-approved drugs and bioactive agents to induce this abrogation signature was evaluated by ligation mediated amplification (LMA) and bead-based fluorescence detection. The screen identified 16 hits confirmed on repeat testing, including seven corticosteroids. Five hits were selected for further study based on their chemical diversity, ability to induce a robust expression signature, and potential for clinical translation: 5-aza-deoxycytidine, floxuridine, methotrexate, methylprednisolone, and pyrimethamine. Next, whole genome effects of these compounds with microarray-based expression profiling were evaluated. Using Gene Set Enrichment Analysis (GSEA), we determined that all five compounds induce both whole genome effects consistent with AML1-ETO knockdown and a whole genome program consistent with neutrophil maturation. In a subset of these compounds, we also see changes in cell surface markers and morphological features consistent with myeloid maturation. Intriguingly, two of the hits are well-characterized DNA methyltransferase inhibitors, and two of the hits are dihydrofolate reductase inhibitors that increase S-adenosylhomocysteine, an inhibitor of methyltransferases. Thus, reversal of AML1-ETO-mediated gene silencing by demethylation may overcome its repressive effects. This application of knockdown-derived expression signatures to small molecule library screening should enable the targeting of nearly any oncogenic transcription factor.
Genomic and biological characterization of aggressive and docile strains of lymphocytic choriomeningitis virus rescued from a plasmid-based reverse-genetics system (2008)

Arenaviruses include several causative agents of haemorrhagic fever disease in humans. In addition, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a superb model for the study of virus-host interactions, including the basis of viral persistence and associated diseases. There is little understanding about the molecular mechanisms concerning the regulation and specific role of viral proteins in modulating arenavirus-host cell interactions either associated with an acute or persistent infection, and associated disease. Here, we report the genomic and biological characterization of LCMV strains 'Docile' (persistent) and 'Aggressive' (not persistent) recovered from cloned cDNA via reverse genetics. Our results confirmed that the cloned viruses accurately recreated the in vivo phenotypes associated with the corresponding natural Docile and Aggressive viral isolates. In addition, we provide evidence that the ability of the Docile strain to persist is determined by the nature of both S and L RNA segments. Thus, our findings provide the foundation for studies aimed at gaining a detailed understanding of viral determinants of LCMV persistence in its natural host, which may aid in the development of vaccines to prevent or treat the diseases caused by arenaviruses in humans.
Ultra-Small Angle X-Ray Scattering (USAXS) <i>in-situ</i> Quantification of Void Network Evolution During Annealing of Nanometer-Sized YSZ Plasma-Sprayed Coatings (2011)

Abstract Suspension plasma spraying (SPS) is able to process a stabilized suspension of nanometer-sized feedstock particles to form thin (from 20 to 100 µm) coatings with unique microstructures. The void network architecture of these ceramic coatings is a challenge to be characterized and quantified using commonly used techniques due to small sizes involved. Nevertheless, the discrimination of these pore architectures in terms of size and shape distribution, anisotropy, specific surface area, etc., is critical for the understanding of processing, microstructure, and properties relationships. USAXS (Ultra-Small Angle X-Rays Scattering) appeared as a suitable measurement technique allowing discriminating the void size distribution over a large range (up to four orders of magnitude). Results indicate that as-sprayed SPS coatings exhibit unusual porous architecture: 1) average void size is about the same than the feedstock one; i.e., nanometer sizes with multimodal void size distribution; 2) about 80% of the voids exhibit characteristic dimensions smaller than 30 nm; 3) the total void content varies between 13 to 20% depending upon considered operating parameters. In-situ annealing measurements were performed as they proved to deliver more relevant results compared to ex-situ measurements: even at temperatures as low as 800°C, the microstructure transforms - while the total void content does not change significantly. Indeed, it has been demonstrated that the smallest voids (equivalent diameters smaller than 50 nm) coalescence was the predominant mechanism and that it was more sensitive to temperature than time.
Transition of Roughness Evolution in Cu–In Alloy Films by the Formation of Intermetallic Compounds (2005)

The evolution of the surface morphology of Cu–In alloy film has been studied using an atomic force microscope. Samples of Cu–In were prepared by sequential vacuum deposition: copper was deposited to 10–40 nm thick first on a glass substrate, followed by the deposition of various amounts of indium to make the indium composition in the range of 0–75 at.%. Samples were prepared under three different conditions: A) deposited at room temperature (RT); B) deposited at RT and annealed at 120°C in vacuo ; and C) deposited at 120°C. Samples formed by A and B (series A and B) showed a growth with a dynamical exponent β of ∼0.3 while the atomic ratio In/Cu was less than 2. The formation of CuIn 2 intermetallic compound was observed by X-ray diffraction as the atomic ratio approached 2. After that, β suddenly increased to ∼0.7, which was attributed to the segregation of excess indium atoms to form cap-shaped islands. For samples grown by C (series C), the roughness initially increased more rapidly with β∼0.7 and decreased above In/Cu∼1. It showed a minimum at In/Cu=2 and finally increased again with β∼0.7 by forming indium islands, as in series A and B.
The Semiconducting Tetragonal Phase of YBa2Cu3O6+<i>x</i> by XPS (1992)

X-ray photoemission spectra from an epitaxial thin film of the tetragonal semiconducting phase of YBa2Cu3O6+x which has been chemically etched in Br2/ethanol are presented. These data are useful for comparison to the orthorhombic superconducting phase.
Laser Weld Reconstitution of Conventional Charpy and Miniaturized Notch Test (MNT) Specimens (1993)

As nuclear power plants approach end-of-license (EOL) and consideration is given to license renewal, there is an ever increasing need to expand the amount of data obtainable from the original surveillance specimens. A laser welding technique to reconstitute broken Charpy specimens is being developed to produce both conventional and miniaturized Charpy specimens. This paper reports on early laser welding development efforts and summarizes previous proof-of-principle experiments on a 1/16 scale miniaturized Charpy test. In order to benchmark the laser welding procedure, the laser-reconstituted specimen data have been compared with the original specimen data. In addition, the microstructure after welding has been examined to ensure that the material in the vicinity of the notch is essentially unchanged after the welding process. Data which characterize the thermal transient during welding are obtained by attaching thermocouples to the specimens. Other important considerations include perturbation of the stress field near the notch, dynamic stress waves, and contact of the weld region with the tup. Precise control of welding parameters has been demonstrated, heat-affected zones as small as 0.25 mm can be achieved, and sufficient penetration depth can be obtained to enable welding thick sections (1T or greater) to yield conventional Charpy specimens or fracture toughness specimens and thin sections (̃5 mm) to yield Miniaturized Notch test (MNT) specimens.
LEARNING STRUCTURED VISUAL DETECTORS FROM USER INPUT AT MULTIPLE LEVELS (2001)

In this paper, we propose a new framework for the dynamic construction of structured visual object/scene detectors for content-based retrieval. In the Visual Apprentice, a user defines visual object/scene models via a multiple-level Definition Hierarchy: a scene consists of objects, which consist of object-parts, which consist of perceptual-areas, which consist of regions. The user trains the system by providing example images/videos and labeling components according to the hierarchy she defines (e.g., image of two people shaking hands contains two faces and a handshake). As the user trains the system, visual features (e.g., color, texture, motion, etc.) are extracted from each example provided, for each node of the hierarchy (defined by the user). Various machine learning algorithms are then applied to the training data, at each node, to learn classifiers. The best classifiers and features are then automatically selected for each node (using cross-validation on the training data). The process yields a Visual Object/Scene Detector (e.g., for a handshake), which consists of an hierarchy of classifiers as it was defined by the user. The Visual Detector classifies new images/videos by first automatically segmenting them, and applying the classifiers according to the hierarchy: regions are classified first, followed by the classification of perceptual-areas, object-parts and objects. We discuss how the concept of Recurrent Visual Semantics can be used to identify domains in which learning techniques such as the one presented can be applied. We then present experimental results using several hierarchies for classifying images and video shots (e.g., Baseball video, images that contain handhakes, skies, etc.). These results, which show good performance, demonstrate the feasibility and usefulness of dynamic approaches for constructing structured visual object/scene detectors from user input at multiple levels.
Membrane Computing: An Introduction (Book Review) (2003)

It would seem that at the moment, computer scientists are showing a ceaseless interest in the world of biology. One would be forgiven in thinking that this is a relatively new phenomenon in Computer Science, but of course it is not. Since the 1950s (maybe even before), biology has been giving food for thought to computer scientists and mathematicians about the nature of computation itself. Biology has been (and continues to be) seen as rich sources of inspiration, both for creating novel approaches to solving computational problems and also for providing new foundations for computation itself i.e. a new way of doing computation. Think of the recent advances in DNA computing: using the natural world to actually DO computation with - a move away from silicon. This book is primarily concerned with a new way of doing computation. However, the book also attempts to engage the reader in the possibility of proving new methods for solving problems, in much the same way as genetic algorithms and the like have over the past few decades. In addition, the book attempts to close the loop between biologically inspired computing (taking ideas from biology) and biologically motivated computing (trying to understand biology using computing) by discussing how it might be possible to shed some more light on to the nature of the biology itself and how that works through the use of membrane computing.
SU-FF-T-519: Potential for Increased Pneumonitis Risk with IMRT as Compared to 3D-CRT for Patients Receiving Adjuvant Chemotherapy: A Radiobiological Modeling Study (2009)

Purpose: Some cytotoxic or molecular targeted drugs increase the risk of radiation therapy toxicity. It is assumed in routine treatment planning that there is no interaction between the radiation dose distribution and the addition of chemotherapy. Here we investigate if the ranking of competing radiation therapy plans with respect to the risk of radiation induced pneumonitis may change when combining radiation with chemotherapy. Method and Materials: Eighteen non-small cell lung cancer (NSCLC) patients previously treated with helical tomotherapy were selected for a modeling study. Three treatment plans were generated for each patient, including: the delivered tomotherapy plan, a 3D conformal radiotherapy (3D-CRT) and a fixed field, intensity modulated radiotherapy (IMRT) plan. The effect of chemotherapy on the normal lung was modeled as an independent cell killing process by adding a uniform, chemotherapy equivalent background dose of radiation to the entire organ at risk. The pneumonitis risk of each plan was estimated using the functional damage (F-DAM) normal tissue complication (NTCP) model. Results: In the case of radiation alone, NTCP values calculated using the F-DAM model predict lower toxicity with both IMRT techniques than with 3D-CRT. However, when a critical chemotherapy equivalent dose is exceeded, this ranking order is reversed and the modeling predicts greater toxicity with both IMRT techniques as compared to 3D-CRT. This critical dose is comparable to the chemotherapy equivalent dose derived from published clinical data. Conclusion: The addition of chemotherapy can influence the optimal choice of radiotherapy technique if not taken into consideration during the treatment planning process. Understanding the interaction of chemotherapy and radiotherapy will improve our ability to predict and potentially minimize the individual risk of adverse effects. Conflict of Interest: Some authors have a financial interest in TomoTherapy Inc.
Transformer Response to System Switching Voltages (1982)

A section of an actual power system was modelled on a Transient Network Analyzer for the purpose of defining high frequency transient voltages occuring during switching events. The variety of system switching events which were staged produced oscillatory voltages covering a broad band of frequencies. On a digital model of the system autotransformers it was demonstrated that such oscillatory voltages could excite internal natural frequencies, but none of the actual generated waves coincided closely with the particular transformer natural frequency. However, if the applied waveshapes were frequency-scaled to a closer match, internal response voltages of concern could be developed.
New Zealand Sauvignon blanc Distinct Flavor Characteristics: Sensory, Chemical, and Consumer Aspects (2009)

A trained sensory panel (n = 14) identified key flavors in Sauvignon blanc wines from Australia, France, New Zealand, Spain, South Africa, and the United States. Sixteen characteristics were identified and measured: sweet sweaty passion fruit, capsicum, passion fruit skin/stalk, boxwood/cat urine, grassy, mineral/flinty, citrus, bourbon, apple lolly/candy, tropical, mint, fresh asparagus, canned asparagus, stone fruit, apple and snow pea. Principal component analysis was used to describe differences among regions and countries. Sauvignon blanc wines from Marlborough, New Zealand, were described by tropical and sweet sweaty passion fruit characteristics, while French and South African Sauvignon blanc wines were described as having flinty/mineral and bourbon-like flavors. Chemical analyses of these wines also showed that wines from Marlborough had more methoxypyrazine and thiol compounds. A consumer study (n = 105) showed that New Zealanders significantly prefer New Zealand-style Sauvignon blanc.
Assessing fast network interfaces (1996)

Assessing the performance of emerging high-speed networks is difficult. Our communication microbenchmark evaluates design changes in a communications system. Our microbenchmark generates a graphical signature from which we extract communication performance parameters for the hardware-software tandem. We use the LogP conceptual model for communication systems. (LogP stands for the parameters latency, overhead, gap, and processors). We study three important platforms that represent diverse points in the network interface design space: the Intel Paragon, Meiko CS-2, and a cluster of Sparcstation-20s connected by Myrinet switches using LANai SBus cards. Our study views each machine as a gray box supporting Active Messages and conforming to the LogP framework. We devise a simple set of communication microbenchmarks and measure the performance on each platform to obtain the LogP parameters.
Analysis of associations of CXCR3 ligands with immune microenvironment and aggressiveness in murine and human pancreatic ductal adenocarcinoma. (2020)

762 Background: The complex milieu of cytokines within pancreatic ductal adenocarcinoma (PDAC) promotes tumor progression and immune suppression thereby contributing to the dismal prognosis of patients with PDAC. However, the roles of many cytokines, including CXCR3 ligands, in PDAC have not been thoroughly investigated. Methods: Bioinformatics analyses of PDAC microarray and TCGA datasets were used to identify cytokines overexpressed in PDAC, their association with patient survival as well as the expression of cognate cytokine receptors. Comparative analysis of cytokine expression in Kras LSL-G12D -P53 LSL-R172H -Pdx1-Cre (KPC) and Kras LSL-G12D -Pdx1-Cre (KC) murine PDAC models were used to validate these findings. Pathway and CIBERSORT analyses were employed to determine mechanistic basis of altered survival associated with cytokines of interest. Results: Of the 149 cytokines analyzed, CXCR3 ligands CXCL9 and CXCL10 were highly and consistently overexpressed in PDAC datasets. Concurrently, CXCL9, CXCL10 and PF4 were overexpressed in the aggressive KPC murine model compared to the indolent KC model. CXCR3 showed robust expression in PDAC in microarray, TCGA and IHC analyses. Interestingly, high expression of CXCR3 ligands was associated with shorter overall survival (p = 0.04 for CXCL9, 10 and 11 and p = 0.02 for PF4) while high expression of CXCR3 was associated with increased overall survival (p = 0.03). Pathway analysis of genes correlated with CXCR3 and/or its ligands showed that CXCR3 ligands may promote T-cell exhaustion (p < 0.001). Finally, CIBERSORT analysis of TCGA data demonstrated that high CXCR3 expression was associated with increased CD8 T-cell and naïve B-cell signatures and loss of plasma cells signatures. High CXCR3 ligand expression was associated with increased CD8 T-cell, and M1 macrophage, and loss of NK-cell signatures(p < 0.05). Conclusions: CXCR3 ligands are overexpressed in PDAC and are associated with poor survival, likely related to alterations in tumor immune infiltrate/activity and may represent targets to augment anti-tumor immunity.
A Novel Vascular Hormone (1996)

The close apposition of the endothelial elements of the vasculature to the smooth muscle provides the anatomic framework for what has been called by some the largest endocrine gland of the body (1). Indeed it is now clear (2,3) that an endothelial cell (EC) not only responds to circulating vasoactive substances, but also produces and releases vasoactive factors adluminally into the blood and abluminally into the adjacent tissue space communicating with vascular smooth muscle cells (VSMC). These factors may act as classical hormones when released into the circulation or more significantly as local paracrine or autocrine agents that control vascular permeability and tone. Peptides, Prostaglandins, and even bioactive gases make up this buffet of locally generated agents, and recent evidence suggests profound interactions of these multiple vasoactive factors describing the control of vascular function. Numerous reviews (4-6) and this entire book categorize and detail the multiple agents that belong to the recently recognized class of vasoactive hormones. Their characterization has led to the development of a new subdiscipline in endocrinology, the endocrinology of the vasculature.
Outcome tools used for ambulatory children with cerebral palsy: responsiveness and minimum clinically important differences (2008)

This prospective longitudinal multicenter study of ambulatory children with cerebral palsy (CP) examined changes in outcome tool score over time, tool responsiveness, and used a systematic method for defining minimum clinically important differences (MCIDs). Three hundred and eighty-one participants with CP (Gross Motor Function Classification System [GMFCS] Levels I-III; age range 4-18y, mean age 11y [SD 4y 4mo]; 265 diplegia, 116 hemiplegia; 230 males, 151 females). At baseline and follow-up at least 1 year later, Functional Assessment Questionnaire, Gross Motor Function Measure, Pediatric Quality of Life Inventory, Pediatric Outcomes Data Collection Instrument, Pediatric Functional Independence Measure, temporal-spatial gait parameters, and oxygen cost were collected. Adjusted standardized response means determined tool responsiveness for nonsurgical (n=292) and surgical (n=87) groups at GMFCS Levels I to III. Most scores reaching medium or large effect sizes were for GMFCS Level III. Nonsurgical group change scores were used to calculate MCID thresholds for ambulatory children with CP. These values were verified by examining participants who changed GMFCS levels. Tools measuring function were responsive when a change large enough to cause a change in GMFCS level occurred. MCID thresholds assess change in study populations over time, and serve as the basis for designing prospective intervention studies.