gebhart/patrepeval huggingface dataset:
Reciprocal activation of Xenobiotic response genes by nuclear receptors SXR/PXR and CAR (2000)

The cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of steroid hormones and xenochemicals including prescription drugs. Nuclear receptor SXR/PXR (steroid and xenobiotic receptor/pregnenolone X receptor) has been shown both biochemically and genetically to activate CYP3A genes, while similar studies have established constitutive androstane receptor (CAR) as a CYP2B regulator. The response elements in these genes are also distinct, furthering the concept of independent regulation. Unexpectedly, we found that SXR can regulate CYP2B, both in cultured cells and in transgenic mice via adaptive recognition of the phenobarbital response element (PBRE). In a type of functional symmetry, orphan receptor CAR was also found to activate CYP3A through previously defined SXR/PXR response elements. These observations not only provide a rational explanation for the activation of multiple CYP gene classes by certain xenobiotics, but also reveal the existence of a metabolic safety net that confers a second layer of protection to the harmful effects of toxic compounds and at the same time increases the propensity for drug-drug interactions.
Fine mapping quantitative trait loci for feed intake and feed efficiency in beef cattle1 (2008)

Feed intake and feed efficiency are economically important traits in beef cattle because feed is the greatest variable cost in production. Feed efficiency can be measured as feed conversion ratio (FCR, intake per unit gain) or residual feed intake (RFI, measured as DMI corrected for BW and growth rate, and sometimes a measure of body composition, usually carcass fatness, RFI(bf)). The goal of this study was to fine map QTL for these traits in beef cattle using 2,194 markers on 24 autosomes. The animals used were from 20 half-sib families originating from Angus, Charolais, and University of Alberta Hybrid bulls. A mixed model with random sire and fixed QTL effect nested within sire was used to test each location (cM) along the chromosomes. Threshold levels were determined at the chromosome and genome levels using 20,000 permutations. In total, 4 QTL exceeded the genome-wise threshold of P < 0.001, 3 exceeded at P < 0.01, 17 at P < 0.05, and 30 achieved significance at the chromosome-wise threshold level (at least P < 0.05). No QTL were detected on BTA 8, 16, and 27 above the 5% chromosome-wise significance threshold for any of the traits. Nineteen chromosomes contained RFI QTL significant at the chromosome-wise level. The RFI(bf) QTL results were generally similar to those of RFI, the positions being similar, but occasionally differing in the level of significance. Compared with RFI, fewer QTL were detected for both FCR and DMI, 12 and 4 QTL, respectively, at the genome-wise thresholds. Some chromosomes contained FCR QTL, but not RFI QTL, but all DMI QTL were on chromosomes where RFI QTL were detected. The most significant QTL for RFI was located on BTA 3 at 82 cM (P = 7.60 x 10(-5)), for FCR on BTA 24 at 59 cM (P = 0.0002), and for DMI on BTA 7 at 54 cM (P = 1.38 x 10(-5)). The RFI QTL that showed the most consistent results with previous RFI QTL mapping studies were on BTA 1, 7, 18, and 19. The identification of these QTL provides a starting point to identify genes affecting feed intake and efficiency for use in marker-assisted selection and management.
The Total Synthesis of Paclitaxel Starting with Camphor (1994)

The first total synthesis of the potent anti-tumor agent taxol is described. The synthesis proceeds from the commodity chemical camphor, which is available in either enantiomeric form, and builds the taxol molecule in a linear fashion. An important feature of the synthetic route is the utilization of conformational control to enable the functionalization of the eight membered B ring of taxol.
A Simple Way to Initialize Recurrent Networks of Rectified Linear Units (2015)

Learning long term dependencies in recurrent networks is difficult due to vanishing and exploding gradients. To overcome this difficulty, researchers have developed sophisticated optimization techniques and network architectures. In this paper, we propose a simpler solution that use recurrent neural networks composed of rectified linear units. Key to our solution is the use of the identity matrix or its scaled version to initialize the recurrent weight matrix. We find that our solution is comparable to LSTM on our four benchmarks: two toy problems involving long-range temporal structures, a large language modeling problem and a benchmark speech recognition problem.
Electron beam inspection system based on the projection imaging electron microscope (2001)

An electron beam inspection system based on the projection imaging electron microscope was developed and the proof-of-concept system has been constructed and evaluated. The secondary electrons are projected through the projection imaging optics and imaged onto the image detection system. The projected secondary electron image is amplified by the microchannel plate and converted to an optical image by the fluorescent screen and detected by the 2048 element, eight-tap time delay and integration (TDI) image sensor. The stage is linearly moved in synchronism with the TDI signal output data rate, and then, the secondary electron image is continuously captured. The spatial resolution of around 0.1 μm has been obtained in this experiment. Several images obtained by the TDI imaging mode are also demonstrated.
Regulation of Androgen Receptor Activity by the Nuclear Receptor Corepressor SMRT (2003)

Androgen receptor (AR) is a hormone-regulated transcription factor that mediates a wide array of biological processes including sexual differentiation, spermatogenesis, and prostate cancer progression. The transcriptional activity of AR and other members of the nuclear receptor superfamily are modulated by coregulatory proteins. In this study, we have investigated the regulation of AR transcriptional activity by the silencing mediator for retinoid and thyroid hormone receptors (SMRT). We found that AR possesses an intrinsic transcriptional repression activity, and AR interacts directly with SMRT. One interacting surface on AR is mapped to the ligand-binding domain, and the presence of a DNA binding/hinge region enhances this interaction. The binding surface on SMRT is mapped to the C-terminal ID2 region, and mutation in the ID2 corepressor motif inhibits the interaction. Overexpression of SMRT inhibits dihydrotestosterone-dependent transactivation by AR and further suppresses the antiandrogen flutamide-mediated inhibition of AR activity. We provide evidence to suggest that the mechanisms of SMRT-mediated inhibition of AR activity involves inhibition of AR N/C interaction and competition with the p160 coactivator. Our data establish a significant role of SMRT in modulating AR transcriptional activity.
Optimized microwave coupling in an electron cyclotron resonance etch tool (1991)

We have improved the operational characteristics of an electron cyclotron resonance (ECR) plasma etch tool by optimizing the coupling of the 2.45-GHz microwaves to the plasma. Improved coupling is achieved by using a right-hand circularly polarized (r.h.c.p.) mode which is matched to the plasma impedance through a quarter-wave transformer. This design reduces microwave reflected power typically to &lt;5% of the incident power without external tuning and simplifies control of the plasma etch tool operation. The r.h.c.p. mode is azimuthally symmetric when averaged over one microwave cycle and adapts easily to ECR source chambers of larger radii. We present an analytic model, the results of which are in good agreement with our experiments for microwave coupling in ECR etch tools.
GLP‐1 <i>C</i>‐terminal structures affect its blood glucose lowering‐function (2008)

Glucagon-like peptide-1 (GLP-1), which is an endogenous insulinotropic peptide that can stimulate islet cells to secret insulin, is a promising new drug candidate for the treatment of type 2 diabetes. However, due to the very short half-life of this peptide, the clinical value of GLP-1 is restricted. A GLP-1 peptide analog that had been altered by deletion of five amino acids from the C-terminus (sGLP-1) was selected and investigated in vivo for the therapeutic effect on GK rats with type II DM (T2DM). The results revealed that sGLP-1 exhibited decreased blood glucose-lowering ability compared to GLP-1 in the first week, as measured after once-daily administration. However, after drug administration for 2 weeks, the blood glucose-lowering effect of sGLP-1 became superior to that of GLP-1. sGLP-1 reduced apoptosis of the old islets, enhanced insulin production, and promoted new islets replication. sGLP-1 is a shorter but more efficient GLP-1 analog for type 2 diabetes management. Because sGLP-1 prolonged the proliferation and recovery of islet cells, the ability to maintain blood glucose (BG) within a normal range was still present 2 weeks after drug withdrawal. These results confirmed the importance of the C-terminus of GLP-1 molecule, and further demonstrated that GLP-1 (7-37) can be truncated till the 32nd amino acid to have a better long-term BG lowing function. This result may imply for the presence of glucagon family clearance receptors in vivo and demonstrates that the C-terminus participates in GLP-1 clearance.
Biology of PSMA As a Diagnostic and Therapeutic Target (2004)

Prostate cancer remains the most common cancer type in men in the United States. Efforts are increasing to evaluate and discover diagnostic and therapeutic markers for prostate cancer patients. One of these, prostate-specific membrane antigen (PSMA), is a transmembrane protein highly expressed in all types of prostatic tissue, especially cancer. The radioimmunoconjugate form of the anti-PSMA monoclonal antibody (MAb) 7E11, known as the ProstaScint® scan, is currently being used to diagnose prostate cancer metastasis and recurrence. The antibody used in the ProstaScint scan recognizes an intracellular epitope of PSMA, making it most accessible in cells that are dead. The ProstaScint antibody is also a mouse antibody that can result in the generation of human anti-mouse antibodies (HAMAs). Therefore second-generation antibodies have been developed that are either genetically engineered humanized antibodies or are fully human antibodies that recognize the extracellular portion of the PSMA protein. Early promising results from various phase I and II trials have demonstrated the utility of PSMA as a target for both imaging and therapy.
Optimisation of active suspension control inputs for improved vehicle handling performance (2016)

Active suspension is commonly considered under the framework of vertical vehicle dynamics control aimed at improvements in ride comfort. This paper uses a collocation-type control variable optimisation tool to investigate to which extent the fully active suspension (FAS) application can be broaden to the task of vehicle handling/cornering control. The optimisation approach is firstly applied to solely FAS actuator configurations and three types of double lane-change manoeuvres. The obtained optimisation results are used to gain insights into different control mechanisms that are used by FAS to improve the handling performance in terms of path following error reduction. For the same manoeuvres the FAS performance is compared with the performance of different active steering and active differential actuators. The optimisation study is finally extended to combined FAS and active front- and/or rear-steering configurations to investigate if they can use their complementary control authorities (over the vertical and lateral vehicle dynamics, respectively) to further improve the handling performance.
Josephson counting analog-to-digital converter (1991)

A superconductive analog-to-digital converter which uses a DC SQUID as a quantizer and a flip-flop counter as a digitizer has been designed, fabricated, and tested. The circuit was fabricated using a ten-level niobium process. Tests at 4.2 K demonstrated counting to the full 12-b accuracy of the design, monotonic A/D conversion with linearity to less than 1 LSB over the more than 9-b range of conversion, read-on-the-fly operation with counter overflow, and counter operation with a gate current bus.
Nouvelles voies d'accès à des aryl‐4 thiéno[2,3‐<i>c</i>]pyridines et à des aryl‐7 thiéno[3,2‐<i>c</i>]pyridines (1981)

Abstract Des aryl‐4 thiéno[2,3‐ c ]pyridines et des aryl‐7 thiéno[3,2‐ c ]pyridines ont été respectivement obtenues par chauffage dans l'acide polyphosphorique de [thényl‐2 amino]‐2 aryl‐1 éthanols ou propanols et de [thényl‐3 amino]‐2 aryl‐1 éthanols ou propanols. La transposition de Beckmann d'oximes d'aryl‐4 dihydro‐4,5 6 H ‐cyclopenta[ b ]thiophènone‐6, conduit à des aryl‐4 dihydro‐4,5 6 H ‐thiéno[2,3‐ c ]pyridones‐7.
Molecular Docking Studies, Synthesis and Biological Evaluation of Substituted Pyrimidine‐2,4‐diamines as Inhibitors of <i>Plasmodium falciparum</i> Dihydrofolate Reductase (2022)

A series of 5-[(phenethylamino)methyl]pyrimidine-2,4-diamines were assessed in silico as potential inhibitors of Plasmodium falciparum dihydrofolate reductase (PfDHFR), synthesised and tested for inhibitory activity against PfDHFR in vitro. The compounds displayed promising inhibitory activity against both wild-type (K<sub>i</sub> 1.3-243 nM) and quadruple mutant (K<sub>i</sub> 13-208 nM) PfDHFR in the biochemical enzyme assay, but were less potent in the whole-cell P. falciparum assay (IC<sub>50</sub> (TM4/8.2) 0.4-28 μM; IC<sub>50</sub> (V1S) 3.7-54 μM). Further investigation into the pharmacokinetic properties of these compounds may guide the development of more potent analogues.
X-ray Diffraction, Solution Structure, and Computational Studies on Derivatives of (3-<i>sec</i>-Butyl-2,3-dihydro-1<i>H</i>-isoquinolin-4-ylidene)acetic Acid: Compounds with Activity as Calpain Inhibitors (2009)

A thorough experimental and computational study of derivatives of (3-sec-butyl-2,3-dihydroisoquinolin-4-ylidene)acetic acid was performed. Some of these compounds are calpain inhibitors and could be useful as therapeutic agents, since this enzyme is a Ca2+-dependent cysteine protease involved in a wide variety of metabolic and physiological processes, whose over-activation is associated to several pathological conditions. To gain a better understanding of the structure−activity relationships, a structural analysis was carried out with 1H and 13C NMR spectroscopy and DFT calculations together with the X-ray diffraction data of three compounds. The solid state structures showed that the crystal packing as well as the intermolecular interactions depend on the substituent nature of the COOR group. Also, the reactivity of the exocyclic double bond was theoretically evaluated, finding that the more reactive compound is the most potent inhibitor of calpain (IC50 = 25 nM).
Conducting polymer nanowires for chemiresistive and FET-based bio/chemical sensors (2010)

Conducting polymer nanostructures are emerging materials with tremendous potential for conductometric/field effect transistor (FET) bio/chemical sensors because of their chemical sensitivity and biocompatibility. Herein, we review recent developments in conducting polymer nanowire-based sensors and discuss the impact of several milestones and continuing challenges. Particular attention is given to device fabrication, nanostructure performance enhancement, and functionalization schemes. Several assembly and integration techniques have been developed for single nanowire devices but significant progress is still needed to improve scalability and manufacturability. Future work should focus on high throughput approaches that enable combinatorial screening of conducting polymer nanowires and heterogeneous, high density arrays of conducting polymer nanostructures, deterministically tailored for targeted analytes. The spatial and temporal resolution of conducting polymer nanowires is addressed along with the origin of the sensitivity enhancement. Functionalization routes add another degree of complexity for biosensors and are discussed in the context of nanosensor performance and device fabrication.
A microelectromechanical-based magnetostrictive magnetometer (1996)

The principles of operation of a microelectromechanical (MEMS)-based magnetometer designed on the magnetoelastic effect are described. The active transduction element is a commercial (001) silicon microcantilever coated with an amorphous thin film of the giant magnetostrictive alloy Terfenol-D [(Dy0.7Te0.3)Fe2]. In addition to the magnetostrictive transducer, basic components of the magnetometer include: (a) mechanical resonance of the coated-microcantilever through coupling to an ac magnetic field; and (b) detection by optical beam deflection of the microcantilever motion utilizing a laser diode source and a position-sensitive detector. Currently, the sensitivity of this MEMS-based magnetostrictive magnetometer is ∼1μT.
<i>In vitro</i> and <i>in vivo</i> testing of a novel, hyperelastic thin film nitinol flow diversion stent (2011)

A flexible, low profile, flow diversion stent could replace endovascular coiling for the treatment of intracranial aneurysms. Micropatterned-thin film nitinol (TFN) is a novel biomaterial with high potential for use in next-generation endovascular devices. Recent advancements in micropatterning have allowed for fabrication of a hyperelastic thin film nitinol (HE-TFN). In this study, the authors describe in vitro and in vivo testing of novel HE-TFN based flow diverting stents. Two types of HE-TFN with expanded pores having long axes of 300 and 500 μm were used to fabricate devices. In vitro examination of the early thrombotic response in whole blood showed a possible mechanism for the device's function, whereby HE-TFN serves as a scaffold for blood product deposition. In vivo testing in swine demonstrated rapid occlusion of model wide-neck aneurysms. Average time to occlusion for the 300-μm device was 10.4 ± 5.5 min. (N = 5) and 68 ± 30 min for the 500-μm device (N = 5). All aneurysms treated with bare metal control stents remained patent after 240 min (N = 3). SEM of acutely harvested devices supported in vitro results, demonstrating that HE-TFN serves as a scaffold for blood product deposition, potentially enhancing its flow-diverting effect. Histopathology of devices after 42 days in vivo demonstrated a healthy neointima and endothelialization of the aneurysm neck region. HE-TFN flow-diverting stents warrant further investigation as a novel treatment for intracranial aneurysms.
Fluorination of Crystalline Polymerized Phases of C<sub>60</sub>Fullerene (2006)

Abstract The reactivity of the orthorhombic (O), tetragonal (T), and rhombohedral (R) polymerized phases of C60 towards gaseous fluorine was studied in the 50–250°C temperature range. It was shown that the reactivity of the polymerized phases greatly surpasses that of C60 and increases during a transition from the O phase to the T‐ and further to R phases. Direct fluorination of the polymerized C60 phases provides an opportunity for production of fluoropolymers of C60 representing a new class of fluorocarbon materials.
A Web-based secure system for the distributed printing of documents and images (2002)

We propose and consider a secure printing system for the distributed printing of documents and images over the World Wide Web. This system enables secure sharing, commerce, and collaboration using images and documents. The main feature of the system is that it allows a user authorized through an authentication. Mechanism to preview and print selected documents and images. The user can then print a certain number of hardcopies, based on an agreed payment. The security of the system resides in an aggregate of communication protocols, smartcard technologies, and cryptographic algorithms. The system prevents eavesdropping so that people who intercept the communication cannot generate copies of the document.
Observation of stacking faults in strained Si layers (2004)

Defects in strained Si layers grown on relaxed SiGe layers were studied using chemical etching and transmission electron microscopy. Defect densities were measured in strained Si layers formed on SiGe buffer layers grown on bulk Si, as well as silicon–germanium-on-insulator substrates. It is found that, in addition to threading dislocations and dislocation pile ups, stacking faults are present in nearly all of the materials studied. The stacking faults are shown to originate in the relaxed SiGe alloy suggesting that they form during the relaxation of the SiGe layer.
Smartphone docking stations and strongly converged VoIP clients for fixed-mobile convergence (2012)

Smartphone docking stations and strongly converged VoIP /Telephony clients are proposed and demonstrated as a new and practical model for fixed-mobile voice and video convergence.
In vivo O‐Space imaging with a dedicated 12 cm<i>Z</i>2 insert coil on a human 3T scanner using phase map calibration (2012)

Recently, spatial encoding with nonlinear magnetic fields has drawn attention for its potential to achieve faster gradient switching within safety limits, tailored resolution in regions of interest, and improved parallel imaging using encoding fields that complement the sensitivity profiles of radio frequency receive arrays. Proposed methods can broadly be divided into those that use phase encoding (Cartesian-trajectory PatLoc and COGNAC) and those that acquire nonlinear projections (O-Space, Null space imaging, radial PatLoc, and 4D-RIO). Nonlinear projection data are most often reconstructed with iterative algorithms that backproject data using the full encoding matrix. Just like conventional radial sequences that use linear spatial encoding magnetic fields, nonlinear projection methods are more sensitive than phase encoding methods to imperfect calibration of the encoding fields. In this work, voxel-wise phase evolution is mapped at each acquired point in an O-Space trajectory using a variant of chemical shift imaging, capturing all spin dynamics caused by encoding fields, eddy currents, and pulse timing. Phase map calibration is then applied to data acquired from a high-power, 12 cm, Z2 insert coil with an eight-channel radio frequency transmit-receive array on a 3T human scanner. We show the first experimental proof-of-concept O-Space images on in vivo and phantom samples, paving the way for more in-depth exploration of O-Space and similar imaging methods.
Zero-Reabsorption Doped-Nanocrystal Luminescent Solar Concentrators (2014)

Optical concentration can lower the cost of solar energy conversion by reducing photovoltaic cell area and increasing photovoltaic efficiency. Luminescent solar concentrators offer an attractive approach to combined spectral and spatial concentration of both specular and diffuse light without tracking, but they have been plagued by luminophore self-absorption losses when employed on practical size scales. Here, we introduce doped semiconductor nanocrystals as a new class of phosphors for use in luminescent solar concentrators. In proof-of-concept experiments, visibly transparent, ultraviolet-selective luminescent solar concentrators have been prepared using colloidal Mn(2+)-doped ZnSe nanocrystals that show no luminescence reabsorption. Optical quantum efficiencies of 37% are measured, yielding a maximum projected energy concentration of ∼6× and flux gain for a-Si photovoltaics of 15.6 in the large-area limit, for the first time bounded not by luminophore self-absorption but by the transparency of the waveguide itself. Future directions in the use of colloidal doped nanocrystals as robust, processable spectrum-shifting phosphors for luminescent solar concentration on the large scales required for practical application of this technology are discussed.