gebhart/patrepeval huggingface dataset:
PCD Technology Advances Sidetracking Capabilities (2000)

Abstract Innovative materials technology advances sidetracking capabilities and offers a cost-effective approach to creating multiple laterals from the same mother bore. The key component to this sidetracking system is a mill designed with polycrystalline diamond (PCD) inserts. Current technology dictates that sidetrack milling be performed with mills dressed with crushed or pre-formed tungsten carbide that is manually applied. Regardless of technology, the success of the sidetrack is dependent upon on the skill and experience of the welder to properly dress the mill. The PCD mill eliminates the dressing process and the related performance uncertainties. This paper discusses how PCD cutters, which are commonly used in drilling, were modified and applied to a casing-sidetracking mill. The mill design capitalizes on their ability to effectively and swiftly cut a window in the casing and drill a rat hole in formations with compressive strengths of up to 40,000 psi. The benefits of such a mill are: 1) using the same cutting element for both steel and hard formations, 2) substantial cost savings when constructing multiple laterals from the same mother bore, 3) increased consistency in mill manufacture, 4) reliable milling performance and 5) improved efficiency in the sidetracking operation. This paper profiles the development and testing from concept to a field-proven tool. The paper details: 1) laboratory-milling tests that identify the best material for cutting steels, 2) Oklahoma field tests in 9-5/8 in. casing to verify the feasibility of PCD casing milling and formation drilling, 3) West Texas and Colombia field runs in operators' 7 and 9-5/8 in. casing to mill a window and drill hard formations. Additionally, the paper will elaborate on the future potential of integrating this technology to a directional drilling assembly to drill laterals with the same equipment and preferably in the same trip for short laterals.
Correlations between the percentage of tumor cells showing an anaplastic lymphoma kinase (<i>ALK</i>) gene rearrangement, <i>ALK</i> signal copy number, and response to crizotinib therapy in <i>ALK</i> fluorescence in situ hybridization–positive nonsmall cell lung cancer (2012)

The strong association between increased copy number of key ALK signals and percentage of positive cells suggests that the <100% rate of cellular positivity in ALK+ tumors is due to technical factors, not biological factors. In ALK+ tumors, neither the percentage of positive cells nor signal copy number appear to be informative variables for predicting benefit from ALK inhibition. The inverse relationship between fused and isolated red copy number suggests ALK+ may be a distinct "near-diploid" subtype of NSCLC that develops before significant chromosomal aneusomy occurs.
Bromodomain inhibitors: what does the future hold? (2018)

Cancer cells are addicted to mutations that cause gain of function in oncogenes and loss of function in tumor suppressors, so that these cells are reliant on aberrant signaling pathways and transcription. Protein-protein and DNA-protein interactions that cause chromatin remodeling are another source of the deregulation of critical signaling and transcriptional regulators, altering epigenetic signatures and creating additional vulnerabilities. Owing to mutations in multiple epigenetic regulators in hematologic malignancies, cancer cells are highly addicted to altered transcription. These vulnerabilities have been targeted by several epigenetic drugs, including hypomethylating agents, but the idea of targeting bromodomain proteins has emerged relatively recently. Because bromodomain proteins recognize acetylated lysine on histones and recruit transcription complexes on the chromatin, targeting these proteins may serve as a strategy to target transcription, irrespective of the presence of epigenetic mutations. Here, we review the existing literature to explain the rationale of using bromodomain inhibitors in hematologic malignancies. We discuss the evolution of bromodomain inhibitors, with an in-depth evaluation of bromodomain and extraterminal domain (BET) proteins, the most prominent bromodomain family, and also highlight the prospect of targeting non-BET proteins. In the later sections, we comment on the combinatorial targeting of BET proteins to overcome the effects of multiple signaling pathways. Finally, we emphasize the newer concepts, such as dual-kinase inhibition and selective bromodomain targeting, and technologies, such as protein degradation, that are expected to influence the future generation of bromodomain inhibitors.
The Epstein-Barr Virus Rta Protein Activates Lytic Cycle Genes and Can Disrupt Latency in B Lymphocytes (1998)

The transition of Epstein-Barr virus (EBV) from latency into the lytic cycle is associated with the expression of two immediate-early viral genes, BZLF1 and BRLF1. Overexpression of ZEBRA, the product of BZLF1, is sufficient to disrupt latency in B lymphocytes and epithelial cells by stimulating expression of lytic cycle genes, including BRLF1. The BRLF1 product Rta functions as a transcriptional activator in both B lymphocytes and epithelial cells. However, Rta has recently been reported to disrupt latency in an epithelial specific manner (S. Zalani, E. Holley-Guthrie, and S. Kenney, Proc. Natl. Acad. Sci. USA 93:9194-9199, 1996). Here we demonstrate that expression of Rta is also sufficient for disruption of latency in a permissive B-cell line. In HH514-16 cells, transfection of Rta leads to synthesis of ZEBRA, viral DNA replication, and late gene expression. However, Rta by itself is less potent than ZEBRA in the ability to activate most early and late lytic cycle genes. In light of previous work implicating ZEBRA in the activation of Rta, we suggest a cooperative model for EBV entry into the lytic cycle. Expression of either BZLF1 or BRLF1 triggers expression of the other immediate-early factor, and together these activators act individually or in synergy on downstream targets to activate the viral lytic cycle.
Antiparallel coupling between Fe layers separated by a Cr interlayer: Dependence of the magnetization on the film thickness (1987)

Spin-polarized low-energy electron diffraction is applied for the first time to study the coupling between ferromagnetic and antiferromagnetic ultrathin films. The remanent magnetization for the epitaxial double-layer structure ${\mathrm{Fe}}_{\mathrm{ii}}$/Cr/${\mathrm{Fe}}_{\mathrm{i}}$/Cr(100) has been monitored in situ during growth. The two Fe slabs (${\mathrm{Fe}}_{\mathrm{ii}}$, ${\mathrm{Fe}}_{\mathrm{i}}$) separated by a thin Cr layer show in-plane antiparallel magnetic coupling along the external magnetic field direction when the two Fe-layer thicknesses differ. The measurements suggest a 90\ifmmode^\circ\else\textdegree\fi{} rotation of the antiparallel magnetization for equal Fe-layer thicknesses.
HER-2, Notch, and Breast Cancer Stem Cells: Targeting an Axis of Evil (2009)

Increasing evidence indicates that tumor-initiating (cancer stem) cells may contribute to treatment resistance and relapse, suggesting that improved clinical outcome will require effective targeting of this cell population. Recent studies suggest that the remarkable clinical efficacy of trastuzumab may relate to its ability to target cancer stem cell populations.
R-Code a Very Capable Virtual Computer (1995)

This thesis investigates the design of a machine independent virtual computer, the R-CODE computer, for use as a target by high level language compilers. Unlike previous machine independent targets, R-CODE provides higher level capabilities, such as a garbage collecting memory manager, tagged data, type maps, array descriptors, register dataflow semantics, and a shared object memory. Emphasis is on trying to find universal versions of these high level features to promote interoperability of future programming languages and to suggest a migration path for future hardware. The memory manager design combines both automatic garbage detection and an explicit "manual" delete operation. It permits objects to be copied at any time, to compact memory or expand objects. It traps obsolete addresses and instantly forwards copied objects using a software cache of an object map. It uses an optimized write-barrier, and is better suited for real-time than a standard copying collector. R-CODE investigates the design of type maps that extend the virtual function tables of C++ and similar tables of HASKELL, EIFFEL, and SATHER 0.6. R-CODE proposes to include numeric types and sizes in type maps, and to inline information from type maps by using dynamic case statements, which switch on a type map identifier. When confronted with a type map not seen before, a dynamic case statement compiles a new case of itself to handle the new type. R-CODE also investigates using IEEE and making array descriptors R-CODE uses a new "register dataflow" execution flow model to better watch the coming generation of superscalar processors. Functional dataflow is used for operations on register values, and memory operations are treated as unordered I/O. Barriers are introduced to sequence groups of unordered memory operations. A detailed semantic execution flow model is presented. R-CODE includes a shared object memory design to support multi-threaded programming within a building where network shared object memory reads and writes take several thousand instruction-execution-times to complete. The design runs on existing symmetric processors, but requires special caches to run on future within-building systems.
Template-directed design of a DNA-DNA crosslinker based upon a bis-tomaymycin-duplex adduct (1992)

A template-directed approach to the design of a DNA-DNA interstrand cross-linker based upon the structure of a bis-tomaymycin-duplex adduct has been carried out. Tomaymycin is a member of the pyrrolo[1,4]benzodiazepines antitumor antibiotics. In a previous study (F.L. Boyd et al., Biochemistry 1990, 29, 2387-2403), we have shown that two tomaymycin molecules can be covalently bound to a 12-mer duplex molecule, where the drug molecules are on opposite strands six base-pairs apart, and the stereochemistry at the drug bonding site, and orientation in the minor groove, was defined by high-field NMR. This bis-tomaymycin 12-mer duplex adduct maintains the self-complementarity of the duplex and a B-type structure. In the present study we have shown using high-field NMR that this same 12-mer sequence can be truncated by two base pairs so that the two tomaymycin-modified guanines are now only four base-pairs apart, the two species of tomaymycin molecules are still bound with the same stereochemistry and orientation, and the 10-mer duplex adduct maintains its self-complementarity. In a second 10-mer duplex we have shown that changing the bonding sequence from 5'CGA to 5'AGC does not significantly affect the structure of the bis-tomaymycin-duplex adduct. However, when the sequence is rearranged so that the drugs point in a tail-to-tail orientation rather than in the previous head-to-head configuration, there are more than one species of tomaymycin bound to DNA, and, as a consequence, the bis-tomaymycin 10-mer duplex adduct loses its self-complementarity. Last, we have used the 10-mer duplex containing the 5'CGA sequence, in which the tomaymycin molecules are oriented head to head, to design an interstrand cross-linking species in which the two drug molecules are linked together with a flexible linker molecule.
CHOBIMALT: A Cholesterol-Based Detergent (2010)

Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems, a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3−4 μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210±30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1.
Reliability Modeling and Optimization Strategy for Manufacturing System Based on RQR Chain (2015)

Accurate and dynamic reliability modeling for the running manufacturing system is the prerequisite to implement preventive maintenance. However, existing studies could not output the reliability value in real time because their abandonment of the quality inspection data originated in the operation process of manufacturing system. Therefore, this paper presents an approach to model the manufacturing system reliability dynamically based on their operation data of process quality and output data of product reliability. Firstly, on the basis of importance explanation of the quality variations in manufacturing process as the linkage for the manufacturing system reliability and product inherent reliability, the RQR chain which could represent the relationships between them is put forward, and the product qualified probability is proposed to quantify the impacts of quality variation in manufacturing process on the reliability of manufacturing system further. Secondly, the impact of qualified probability on the product inherent reliability is expounded, and the modeling approach of manufacturing system reliability based on the qualified probability is presented. Thirdly, the preventive maintenance optimization strategy for manufacturing system driven by the loss of manufacturing quality variation is proposed. Finally, the validity of the proposed approach is verified by the reliability analysis and optimization example of engine cover manufacturing system.
LpxC Inhibitors: Design, Synthesis, and Biological Evaluation of Oxazolidinones as Gram-negative Antibacterial Agents (2016)

Herein we report a scaffold-hopping approach to identify a new scaffold with a zinc binding headgroup. Structural information was used to give novel oxazolidinone-based LpxC inhibitors. In particular, the most potent compound, 23j, showed a low efflux ratio, nanomolar potencies against E. coli LpxC enzyme, and excellent antibacterial activity against E. coli and K. pneumoniae. Computational docking was used to predict the interaction between 23j and E. coli LpxC, suggesting that the interactions with C207 and C63 contribute to the strong activity. These results provide new insights into the design of next-generation LpxC inhibitors.
P2P-based collaborative media streaming for heterogeneous network terminals (2008)

In this paper, we present a receiver centric P2P-based multimedia streaming mechanism for heterogeneous network terminals. P2P networks possess the heterogeneous characteristics that are not known a priori, such dynamic conditions make the real time applications like multimedia streaming more challenging. We proposed an adaptive streaming mechanism to cope with the problem of dynamic characteristics and to meet the requirement of heterogeneous network terminals. The key characteristics of the mechanism include, media-aware, network-aware, and quality-aware. The main objective of this proposed streaming mechanism is to maximize the received throughput (total number of received packets) and to minimize the packet drop ratio in order to improve the overall Quality of Service (QoS). We evaluated the proposed P2P streaming mechanism by performing simulations using NS-2. The obtained results show a considerable improvement in the overall received QoS.
Predicting Mood from Punctual Emotion Annotations on Videos (2015)

A smart environment designed to adapt to a user's affective state should be able to decipher unobtrusively that user's underlying mood. Great effort has been devoted to automatic punctual emotion recognition from visual input. Conversely, little has been done to recognize longer-lasting affective states, such as mood. Taking for granted the effectiveness of emotion recognition algorithms, we propose a model for estimating mood from a known sequence of punctual emotions. To validate our model experimentally, we rely on the human annotations of two well-established databases: the VAM and the HUMAINE. We perform two analyses: the first serves as a proof of concept and tests whether punctual emotions cluster around the mood in the emotion space. The results indicate that emotion annotations, continuous in time and value, facilitate mood estimation, as opposed to discrete emotion annotations scattered randomly within the video timespan. The second analysis explores factors that account for the mood recognition from emotions, by examining how individual human coders perceive the underlying mood of a person. A moving average function with exponential discount of the past emotions achieves mood prediction accuracy above 60 percent, which is higher than the chance level and higher than mutual human agreement.
The Human Capability Framework Ten Years On (2009)

This paper considers the human capability framework (the framework) from a policy practitioners' perspective. It outlines the genesis of the framework, its uses, and reflects on its utility as a conceptual framework to examine labour market issues. The labour market has changed considerably over the past decade, and the paper examines the framework's ability to provide insights into the new challenges and emphasis that this requires.
Crystal Structure of β-Ketoacyl-Acyl Carrier Protein Synthase III (1999)

Beta-ketoacyl-acyl carrier protein synthase III (FabH), the most divergent member of the family of condensing enzymes, is a key catalyst in bacterial fatty acid biosynthesis and a promising target for novel antibiotics. We report here the crystal structures of FabH determined in the presence and absence of acetyl-CoA. These structures display a fold that is common for condensing enzymes. The observed acetylation of Cys(112) proves its catalytic role and clearly defines the primer binding pocket. Modeling based on a bound CoA molecule suggests catalytic roles for His(244) and Asn(274). The structures provide the molecular basis for FabH substrate specificity and reaction mechanism and are important for structure-based design of novel antibiotics.
Electro-optic diffraction grating for light beam modulation and diffraction (1965)

The interaction between a strong traveling microwave signal and an optical beam in an electro-optic material is described in the limit of very high microwave dielectric constant. The interaction produces effects analogous to those produced by a moving diffraction grating. When the optical beam is wider than the wavelength of the microwave signal, the first grating order is resolved from the zero-order or main beam. Under this condition two types of devices become possible: 1) a beam deflector which can position an optical maser beam on, for example, 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> distinct points with negligible crosstalk and with address times of order 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-7</sup> s, 2) a baseband light intensity modulator which is founded on the fact that light deflected into the first-order beam by the microwave signal is removed from the main beam. The amount deflected into the first-order beam is proportional to the microwave power; the intensity modulation follows the microwave envelope. The power required for a given modulation depth is inversely proportional to the seven halfs power of the dielectric Constant. As an example, for a not unrealistic choice of dielectric constant of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> , complete transfer from the zero-order to the first-order beam requires 5 watts of microwave power. The interaction length is of order one centimeter and the interaction bandwidth is essentially unlimited. As a baseband modulator the maximum instantaneous bandwidth is of order 10 percent of the subcarrier frequency. Experimental verification is provided in an earlier paper [1].
CONTENTS (2011)

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Fragment-Based Discovery of New Highly Substituted 1<i>H</i>-Pyrrolo[2,3-<i>b</i>]- and 3<i>H</i>-Imidazolo[4,5-<i>b</i>]-Pyridines as Focal Adhesion Kinase Inhibitors (2013)

Focal adhesion kinase (FAK) is considered as an attractive target for oncology, and small-molecule inhibitors are reported to be in clinical testing. In a surface plasmon resonance (SPR)-mediated fragment screening campaign, we discovered bicyclic scaffolds like 1H-pyrazolo[3,4-d]pyrimidines binding to the hinge region of FAK. By an accelerated knowledge-based fragment growing approach, essential pharmacophores were added. The establishment of highly substituted unprecedented 1H-pyrrolo[2,3-b]pyridine derivatizations provided compounds with submicromolar cellular FAK inhibition potential. The combination of substituents on the bicyclic templates and the nature of the core structure itself have a significant impact on the compounds FAK selectivity. Structural analysis revealed that the appropriately substituted pyrrolo[2,3-b]pyridine induced a rare helical DFG-loop conformation. The discovered synthetic route to introduce three different substituents independently paves the way for versatile applications of the 7-azaindole core.
TREATMENT WITH H2S-RELEASING DICLOFENAC PROTECTS MICE AGAINST ACUTE PANCREATITIS-ASSOCIATED LUNG INJURY (2007)

Impaired lung function in severe acute pancreatitis is the primary cause of morbidity and mortality in this condition. Hydrogen sulfide (H(2)S) is a naturally occurring gas that has been shown to be a potent vasodilator. Diclofenac is a nonsteroidal anti-inflammatory drug and has been shown to have anti-inflammatory, analgesic, and antipyretic activity. ACS15 is an H(2)S-releasing derivative of diclofenac. Little is known about its effectiveness as an anti-inflammatory drug. In this report, we describe the effect of diclofenac and its H(2)S-releasing derivative on acute pancreatitis and associated lung injury in the mouse. Acute pancreatitis was induced in mice by hourly i.p. injections of cerulein. Diclofenac and ACS15 were administered either 1 hour before or 1 hour after starting cerulein injections, and the severity of acute pancreatitis and associated lung injury was assessed. The severity of acute pancreatitis was determined by hyperamylasemia, neutrophil sequestration in the pancreas (pancreatic myeloperoxidase activity), and pancreatic acinar cell injury/necrosis on histological examination of pancreas sections. The severity of acute pancreatitis-associated lung injury was assessed by neutrophil sequestration in the lungs (lung myeloperoxidase activity) and by histological examination of lung sections. ACS15, given prophylactically and therapeutically, significantly reduced lung inflammation without having any significant effect on pancreatic injury. These results suggest the usefulness of H(2)S-releasing nonsteroidal anti-inflammatory drugs as potential treatments for pancreatitis-associated lung injury.
Jenkins: The Definitive Guide (2011)

Streamline software development with Jenkins, the popular Java-based open source tool that has revolutionized the way teams think about Continuous Integration (CI). This complete guide shows you how to automate your build, integration, release, and deployment processes with Jenkins-and demonstrates how CI can save you time, money, and many headaches. Ideal for developers, software architects, and project managers, Jenkins: The Definitive Guide is both a CI tutorial and a comprehensive Jenkins reference. Through its wealth of best practices and real-world tips, you'll discover how easy it is