gebhart/patrepeval huggingface dataset:
Synthesis, Biological Evaluation, and Three-Dimensional Quantitative Structure−Activity Relationship Study of Small-Molecule Positive Modulators of Adrenomedullin (2005)

Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation and in the pathophysiology of several diseases such as hypertension, cancer, diabetes, and renal disorders, becoming an interesting new target for the development of drugs. In a recent high-throughput screening study, a positive modulator with a bistriazole structure has been identified.(1) In this work, a new series of structurally related compounds has been synthesized by reaction of phenoxyacetic acid with the corresponding dihydrazide, followed by treatment of the formed bisoxadiazoles with benzylamine. The affinity toward AM of the lead compound, and a structurally related family obtained from the small-molecule NCI library together with the synthesized series, has been determined. A three-dimensional quantitative structure-activity relationship (3D-QSAR) study and conformational and molecular dynamics simulations have shown that the presence of a free NH and a phenyl group is essential for the interaction of these compounds with AM.
A line of non‐tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth (1987)

An immortal line of pigmented melanocytes, "melan-a", has been derived from normal epidermal melanoblasts from embryos of inbred C57BL mice. The conditions favouring proliferation of these cells largely resemble those for normal, non-established mouse melanoblasts and melanocytes, and include a low extracellular pH and the presence of a tumour promoter, tetradecanoyl phorbol acetate (TPA) or teleocidin. Melan-a cells have the diploid chromosome number and do not form tumours in syngeneic or nude mice. They are therefore the first known line of non-tumorigenic mouse melanocytes, although an aneuploid melanocyte line of untested tumorigenicity has been reported (Sato et al., 1985). Melan-a cells are syngeneic with the B16 melanoma and its sublines, and provide an excellent parallel non-tumorigenic line for studies of the cellular and molecular basis of melanoma malignancy.
A constraint-based god-object method for haptic display (2002)

Haptic display is the process of applying forces to a human "observer" giving the sensation of touching and interacting with real physical objects. Touch is unique among the senses because it allows simultaneous exploration and manipulation of an environment. A haptic display system has three main components. The first is the haptic interface, or display device, generally some type of electro-mechanical system able to exert controllable forces on the user with one or more degrees of freedom. The second is the object model-a mathematical representation of the object containing its shape and other properties related to the way it feels. The third component, the haptic rendering algorithm, joins the first two components to compute, in real time, the model-based forces to give the user the sensation of touching the simulated objects. This paper focuses on a new haptic rendering algorithm for generating convincing interaction forces for objects modeled as rigid polyhedra. We create a virtual model of the haptic interface, called the god-object, which conforms to the virtual environment. The haptic interface can then be servo-ed to this virtual model. This algorithm is extensible to other functional descriptions and lays the groundwork for displaying not only shape information, but surface properties such as friction and compliance.
Ghost imaging, quantum and classical aspects (2004)

We analytically show that it is possible to perform coherent imaging by using the classical correlation of two beams obtained by splitting incoherent thermal radiation. A formal analogy is demonstrated between two such classically correlated beams and two entangled beams produced by parametric down-conversion. Because of this analogy, the classical beams can mimic qualitatively all the imaging properties of the entangled beams, even in ways which up to now were not believed possible. A key feature is that these classical beams are spatially correlated both in the near-field and in the far-field. Using realistic numerical simulations the performances of a quasi-thermal and a parametric down-conversion source are shown to be closely similar, both for what concerns the resolution and statistical properties. The results of this paper provide a new scenario for the discussion of what role the entanglement plays in correlated imaging.
Efficiency Analysis of Magnetic Resonance Wireless Power Transfer With Intermediate Resonant Coil (2011)

This letter presents an efficiency analysis of a magnetic resonance wireless power transfer (WPT) system with an intermediate resonant coil. A helical coil and a spiral coil with an additional capacitor are considered as resonant coils for the WPT system. The intermediate resonant coil is set up coaxially and perpendicular to both the Tx and Rx resonant coils in order to observe the efficiency change according to the directions. The power efficiency is calculated using the temporal coupled mode theory (CMT). Impedance matching conditions are also shown by using the CMT. Analysis results show that using an intermediate coil properly improves efficiency and extends the distance between the transmitter and receiver. Both calculated and measured efficiencies are in good agreement. It is also shown that the intermediate resonant system has a good efficiency and is superior to nonintermediate systems.
Modulation of luminescence operon expression by N-octanoyl-L-homoserine lactone in ainS mutants of Vibrio fischeri (1996)

Population density-dependent expression of luminescence in Vibrio fischeri is controlled by the autoinducer N-3-oxohexanoyl-L-homoserine lactone (autoinducer 1 [AI-1]), which via LuxR activates transcription of the lux operon (luxICDABEG, encoding the putative autoinducer synthase [LuxI] and the luminescence enzymes). We recently identified a novel V. fischeri locus, ainS, necessary for the synthesis of a second autoinducer, N-octanoyl-L-homoserine lactone (AI-2), which via LuxR can activate lux operon transcription in the absence of AI-1. To define the regulatory role of AI-2, a luxI ainS double mutant was constructed; in contrast to the parental strain and a luxI mutant, the luxI ainS mutant exhibited no induction of luminescence and produced no detectable luminescence autoinducer, demonstrating that V. fischeri makes no luminescence autoinducers other than those whose synthesis is directed by luxI and ainS. A mutant defective only in ainS exhibited accelerated luminescence induction compared with that of the parental strain, indicating that AI-2 functions in V. fischeri to delay luminescence induction. Consistent with that observation, the exogenous addition of AI-2 inhibited induction in a dose-dependent manner in V. fischeri and Escherichia coli carrying the lux genes. AI-2 did not mediate luxR negative autoregulation, alone or in the presence of AI-1, and inhibited luminescence induction in E. coli regardless of whether luxR was under the control of its native promoter or a foreign one. Increasing amounts of AI-1 overcame the inhibitory effect of AI-2, and equal activation of luminescence required 25- to 45-fold-more AI-2 than AI-1. We conclude that AI-2 inhibits lux operon transcription. The data are consistent with a model in which AI-2 competitively inhibits the association of AI-1 with LuxR, forming a complex with LuxR which has a markedly lower lux operon-inducing specific activity than that of AI-1-LuxR. AI-2 apparently functions in V. fischeri to suppress or delay induction at low and intermediate population densities.
Learning Sparse Neural Networks through $L_0$ Regularization (2017)

We propose a practical method for $L_0$ norm regularization for neural networks: pruning the network during training by encouraging weights to become exactly zero. Such regularization is interesting since (1) it can greatly speed up training and inference, and (2) it can improve generalization. AIC and BIC, well-known model selection criteria, are special cases of $L_0$ regularization. However, since the $L_0$ norm of weights is non-differentiable, we cannot incorporate it directly as a regularization term in the objective function. We propose a solution through the inclusion of a collection of non-negative stochastic gates, which collectively determine which weights to set to zero. We show that, somewhat surprisingly, for certain distributions over the gates, the expected $L_0$ norm of the resulting gated weights is differentiable with respect to the distribution parameters. We further propose the \emph{hard concrete} distribution for the gates, which is obtained by "stretching" a binary concrete distribution and then transforming its samples with a hard-sigmoid. The parameters of the distribution over the gates can then be jointly optimized with the original network parameters. As a result our method allows for straightforward and efficient learning of model structures with stochastic gradient descent and allows for conditional computation in a principled way. We perform various experiments to demonstrate the effectiveness of the resulting approach and regularizer.
Neat Uhmwpe Filament Wound Composites by Crosslinking Compaction (2003)

A novel hot compacted crosslinked filament wound structure was prepared form Ultra High Molecular Weight Polyethylene fibres, characterized and shown to possess improved properties. Three different compaction temperatures (140°C, 145°C and 150°C) were tested for both crosslinked and non-crosslinked control systems. The optimal temperature for the hot compaction process was selected on the basis of maximum fibre skin melting for better fibre-fibre fusion and tensile strength, combined with minimum core melting for higher Young's modulus. The crosslinked compacts exhibited better mechanical properties than the non-crosslinked ones; for example, for compacts prepared at 145°C the tensile strength was higher by about 55% and the Young's modulus by about 36%, respectively. The improvement was attributed to stronger fibre-fibre bonding via the crosslinked network formed at their skins. From the chemical surface analysis it could be concluded that some 43%) of the C-H groups at the fibre surface turned into C-C bonds as a result of the crosslinking compaction process.
Influenza A Virus NS1 Protein Activates the PI3K/Akt Pathway To Mediate Antiapoptotic Signaling Responses (2007)

Recently we have shown that influenza A virus infection leads to activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and that this cellular reaction is dependent on the expression of the viral nonstructural protein 1 (NS1). These data also suggested that PI3K activation confers a virus-supporting activity at intermediate stages of the infection cycle. So far it is not known which process is regulated by the kinase that supports virus replication. It is well established that upon infection with influenza A virus, the expression of the viral NS1 keeps the induction of beta interferon and the apoptotic response within a tolerable limit. On a molecular basis, this activity of NS1 has been suggested to preclude the activation of cellular double-stranded RNA receptors as well as impaired modulation of mRNA processing. Here we present a novel mode of action of the NS1 protein to suppress apoptosis induction. NS1 binds to and activates PI3K, which results in the activation of the PI3K effector Akt. This leads to a subsequent inhibition of caspase 9 and glycogen synthase-kinase 3beta and limitation of the virus-induced cell death program. Thus, NS1 not only blocks but also activates signaling pathways to ensure efficient virus replication.
Tocilizumab: The first interleukin-6-receptor inhibitor (2008)

Tocilizumab, a novel IL-6R inhibitor, may be beneficial for the treatment of RA in patients who do not respond to methotrexate or disease-modifying antirheumatic drugs. A large clinical trial is needed to confirm tocilizumab's clinical efficacy and safety.
ORGANELLES AND TRAFFICKING MACHINERY FOR POSTSYNAPTIC PLASTICITY (2006)

Neurons are among the largest and most complex cells in the body. Their immense size and intricate geometry pose many unique cell-biological problems. How is dendritic architecture established and maintained? How do neurons traffic newly synthesized integral membrane proteins over such long distances to synapses? Functionally, protein trafficking to and from the postsynaptic membrane has emerged as a key mechanism underlying various forms of synaptic plasticity. Which organelles are involved in postsynaptic trafficking, and how do they integrate and respond to activity at individual synapses? Here we review what is currently known about long-range trafficking of newly synthesized postsynaptic proteins as well as the local rules that govern postsynaptic trafficking at individual synapses.
The role of nuclear factor kappa B in human labour (2005)

Preterm birth remains the leading cause of perinatal mortality and morbidity, largely as a result of a poor understanding of the precise mechanisms controlling labour onset in humans. Inflammation has long been recognised as a key feature of both preterm and term labour, with an influx of inflammatory cells into the uterus and elevated levels of pro-inflammatory cytokines observed during parturition. Nuclear factor kappa B (NF-kappaB) is a transcription factor family classically associated with inflammation. Accumulating evidence points to a role for NF-kappaB in the physiology and pathophysiology of labour. NF-kappaB activity increases with labour onset and is central to multiple prolabour pathways. Premature or aberrant activation of NF-kappaB may thus contribute to preterm labour. The current understanding of NF-kappaB in the context of human labour is discussed here.
Algorithms and techniques for manufacturing (1996)

This dissertation investigates the application of computer science techniques to tasks in manufacturing. Many of these techniques are founded upon three underlying approaches: machine vision techniques, generate and test techniques, and classical algebraic geometry techniques. The ten main algorithms presented in this thesis are: recognizing and localizing prismatic parts using a crossbeam sensor, recognizing and localizing prismatic parts using a scanning beam sensor, constructing complete indexing tables to recognize objects from crossbeam sensor data and scanning beam sensor data, localizing features of dissimilar types, enumerating all fixture configurations capable of immobilizing a given prismatic polyhedral object, enumerating all fixture configurations capable of immobilizing a given prismatic generalized polyhedral object, reducing the problem of enumerating modular fixture designs to the problem of constructing complete indexing tables, constructing complete indexing tables for generic systems, using tree grid structures to compact indexing tables, calibrating point probe and line probe sensors, and calibrating the end effector arm of high precision manipulators. We discuss the implementation of these algorithms and their performance on a number of examples. These techniques are also applicable to other problems in computer vision, and robotics.
The thesis consists of twelve chapters. Each chapter has been organized independently. Chapter 1 gives a brief overview of the thesis. In Chapter 2 we present the algorithm for recognizing and localizing prismatic parts using a crossbeam sensor, and discuss its implementation and performance. Chapter 3 describes the algorithm for recognizing and localizing parts using a scanning beam sensor and provide performance measurements. In Chapter 4, we present an exact algorithm for localizing features of dissimilar types by reducing it to a nonlinear least squares problem which is solved using a combination of algebraic and numerical techniques. In Chapter 5, we discuss a complete modular fixture design algorithm which efficiently enumerates all fixture configurations for immobilizing a given prismatic polyhedral workpiece. In Chapter 6, we extend this algorithm to handle prismatic generalized polyhedral workpieces. In Chapter 7, we discuss the duality between modular fixturing and scanning which provides a generic algorithm for designing fixtures for arbitrary workpieces and arbitrary minimal fixture toolkits. In Chapter 8, we describe a technique for constructing complete indexing tables, thereby enabling indexing techniques to be used for systems which do not exhibit invariants. In Chapter 9, we describe the tree grid indexing mechanism which reduces the size of indexing tables, and also provides for coherent searches. In Chapters 10 and 11, we discuss calibration issues which are prerequisites for exploiting the high precisions achieved by the sensing strategies. Finally, in Chapter 12 we conclude the thesis and discuss problem areas for future research.
One-Step Low-Temperature Route for the Preparation of Electrochemically Active LiMnPO4 Powders (2003)

Pure and well-crystallized LiMnPO4 powders were obtained by a direct precipitation route in an aqueous medium at 373 K. A thermodynamic study of the system Li+/Mn(II)/phosphate/H2O identified a pH range in which LiMnPO4 precipitation was the most probable. From these theoretical considerations, the olivine-type compound precipitation turned out to be straightforward, i.e., no further thermal treatment was needed. A systematic study of the influence of synthesis parameters enabled tailoring of the size of the as-obtained particles. The smallest precipitated particles (∼100 nm) led to a global improvement of the electrochemical behavior when used in lithium batteries, consisting in lowering the polarization and enhancement of the reversible capacities (∼70 mAh/g at C/20). A two-phase Li extraction/insertion mechanism was identified, using the potential intermittent titration technique (PITT) and in situ X-ray diffraction, between LiMnPO4 and the delithiated phase MnPO4, indexed in the space group Pmnb with unit cell parameters a = 5.93(2) Å, b = 9.69(6) Å, and c = 4.78(1) Å.
Binding of an optically pure photoaffinity analogue of verapamil, LU-49888, to P-glycoprotein from multidrug-resistant human leukemic cell lines. (1990)

Verapamil enhances anticancer drug cytotoxicity in multidrug resistant (MDR) cells, apparently by competing with these agents for binding to P-glycoprotein (Pgp). In this study, we provide direct evidence for this competition. We studied the binding of an optically pure photoaffinity analogue of verapamil, (S)-5-[(3-azidophenylethyl)-[N-methyl-3H]- methylamino]-2-(3,4,5-trimethoxyphenyl)-2-isopropylvaleronitrile (LU-49888), to Pgp from MDR cell lines. LU-49888 specifically labeled a single Mr 170,0000 protein that was identified as Pgp on Western blots and also by specific immunoprecipitation with monoclonal antibody C-219. A 200-fold molar excess of vinblastine or vincristine specifically inhibited this binding by greater than 98%. LU-49888 labeling of Pgp was also inhibited by actinomycin D (45%), podophyllotoxin (47%), and amsacrine (82%), marginally by doxorubicin (25%), colchicine (22%), daunorubicin (18%), and etoposide (14%), but not by teniposide. Modulators of Pgp-MDR also compete with LU-49888 for binding to Pgp: verapamil (82%), diltiazem (73%), quinidine (91%), reserpine (91%), rescinnamine (88%), and trimethoxybenzoylyohimbine (89%). Chloroquine was moderately inhibitory (25%), whereas chlorpromazine and yohimbine, which are not modulators in our MDR cell lines, did not inhibit the binding of LU-49888 to Pgp. LU-49888 labeling of Pgp was also completely inhibited by (R)-, (S)-, and racemic desmethoxyverapamil, all with the same efficiency. Our results demonstrate that the verapamil analogue LU-49888 specifically binds to Pgp and suggest that verapamil and some MDR modulators exert their effects by interacting with Pgp.
Detection of occult atrial fibrillation in patients with embolic stroke of uncertain source: a work in progress (2015)

Atrial fibrillation accounts for a substantial proportion of ischemic strokes of known etiology and may be responsible for an additional subset of the 25-40% of strokes of unknown cause (so-called cryptogenic). Oral anticoagulation is significantly more effective than antiplatelet therapy in the secondary prevention of atrial fibrillation-related strokes, providing justification for developing more sensitive approaches to detecting occult paroxysms of atrial fibrillation. In this article, we summarize the current state of knowledge regarding the value of in-hospital and out-patient monitoring for detecting atrial fibrillation in the context of cryptogenic stroke. We review the evidence for and against screening with standard Holter monitors, external loop recorders, the newer real-time continuous attended cardiac monitoring systems, cardiac implantable electronic devices, and insertable loop recorders. We review key questions regarding prolonged cardiac arrhythmia monitoring, including the relationship between duration of the atrial fibrillation episode and risk of thromboembolism, frequency of monitoring and its impact on the diagnostic yield in detecting occult or subclinical atrial fibrillation, and the temporal proximity of device-detected atrial fibrillation to stroke events. We conclude by proposing avenues for further research.
Altered N-Glycan Expression Profile in Epithelial-to-Mesenchymal Transition of NMuMG Cells Revealed by an Integrated Strategy Using Mass Spectrometry and Glycogene and Lectin Microarray Analysis (2014)

Epithelial-to-mesenchymal transition (EMT) is an essential biological process that occurs in embryonic development, metastatic diseases, and cancer progression. Altered expression of glycans is known to be associated with cancer progression. No studies to date have presented global analysis of the precise variation of N-glycans in EMT. We describe here the profile of N-glycans and glycogene expression in the EMT process induced by transforming growth factor-β1 (TGFβ1) in a normal mouse mammary gland epithelial (NMuMG) cell model. An integrated strategy with a combination of mass spectrometry, glycogene microarray analysis, and lectin microarray analysis was applied, and results were confirmed by lectin histochemistry and quantitative real-time PCR. In TGFβ-induced EMT, levels of high-mannose-type N-glycans were enhanced, antennary N-glycans, and fucosylation were suppressed, and bisecting GlcNAc N-glycans were greatly suppressed. The expression of seven N-glycan-related genes was significantly changed. The products of glycogenes ALG9, MGAT3, and MGAT4B appeared to contribute to the observed alteration of N-glycans. The findings indicate that dysregulation of N-glycan synthesis plays a role in the EMT process. Systematic glycomic analysis based on the combination of techniques described here is expected to facilitate the discovery of the aberrant N-glycosylation in tumor progression and provide essential information in systems glycobiology.