gebhart/patrepeval huggingface dataset:
Abstract 3892: Anti-cooperative allosteric inhibitors of thymidylate synthase as novel antineoplastic agents (2012)

Abstract Thymidylate synthase (TS) inhibitors are a class of antineoplastic agents widely used for the treatment of gastrointestinal, breast, ovarian and other cancers. TS catalyzes reductive methylation of dUMP to dTMP and serves as the sole de novo source of thymidylate inside the cell. While TS is essential for DNA biosynthesis and normal cell proliferation, TS overexpression has been associated with resistant tumor phenotype and poor prognosis. Although TS inhibitor 5-flourouracil (5-FU) continues to be one of the most frequently used chemo-therapeutic agents, 5-FU and its metabolites can cause significant liver, cardiac and bone marrow toxicity and are associated with development of drug resistance. In this study, we developed a new strategy that targets TS subunit cooperativity by freezing isoform interconversions and structural dynamics of the enzyme. In TS catalytic mechanism, conserted motion of amino acid residues 181-197 brings the catalytic Cys195 in and out of the active site. These small scale motions that translate across the dimer interface upon substrate binding and product release are integral to TS enzymatic function and can be taken advantage of in structure-based design of its inhibitors. For this purpose, we selected TS crystal structure with high asymmetry between the subunits (PDBID:1HVY) and used it as a template for molecular docking. The structure was prepared by removing heteroatoms and liganded molecules, followed by energy minimization in UCSF Chimera (1.5.2) and testing resulting geometries in Coot (0.6.2). We identified 5 potential docking sites and selected the site at the dimer interface specific to inactive conformation of TS. National Cancer Institute (NCI) small molecule library of 139,735 compounds was extracted from ZINC and pruned for redundant structures and molecules with molecular weight less than 200 Da. Resulting compound library was docked (DOCK6.4) into the selected site in 1000 orientations with flexible bond parameters enabled. The top 1000 hits were re-scored using AMBER and visualized in PyMOL to check for consistency and geometric fit. 837 out of 1000 molecules were further selected and re-ranked based on predicted physicochemical characteristics (cLogP, pKa, solubility, etc.). The twenty-seven highest ranked compounds were requested from the NCI and tested for their effects on viability in HeLa, K562 and A549 human cancer cell lines. Five out of 27 compounds reduced viability by more than 50% at a concentration of 10uM; one of the compounds was effective below 1uM. In conclusion, by using this new approach that targets TS subunit cooperativity, we identified small molecules with potential anti-cancer activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3892. doi:1538-7445.AM2012-3892
A wireless sensor network for residential electrical energy consumption measurement (2012)

A wireless sensor network for residential electrical energy consumption measurements is presented. The system integrates wireless sensors to measure the energy consumption of individual electrical circuits in a breaker panel. Each sensor is battery-powered and transmits its data using the 802.15.4 wireless protocol to a communication hub which forwards the aggregated data to a server via Ethernet or Wi-Fi. The sensors use Hall-effect current sensors, a microcontroller, two button-cell batteries and a wireless transmitter. The sensors accuracy is better than 0.8 A on a range of 0–30 A.
Development of Eddy Current Testing System for Complicated-Shaped Components (2008)

The objectives of this study are to develop a new inspection probe for complex structures using eddy current testing method (ECT), to establish the recognition technique of real flaw shape such as stress corrosion cracking (SCC), and to develop a rapid nondestructive inspection system. An ECT system consists of measurement and computational modules that are connected via a network circuit. The measurement module includes a flexible ECT sensor, which could fit on the curvature surface of radius larger than 25 mm with a mechanical manipulator. The computational module is used for SCC sizing. It includes a database of ECT signals that are used to execute numerical calculations. SCC sizing can be evaluated by comparing the measured ECT signals with the calculated ECT signals within the database. We have demonstrated that the system could be used to estimate the SCC length and depth sizing in 140 s. The accuracy of length sizing showed an RMS error of 3.7 mm and the depth sizing was 0.63 mm in this work.
Order Statistics-Based Design of UWB Receivers (2020)

We propose a non-coherent ultra-wideband (UWB) receiver that leverages a single-sample-per-pulse threshold approach to detect the transmitted symbol and is capable of mitigating the impact of impulse noise. Unlike classical detectors, the proposed receiver does not aim for the peak (-order) sample, rather it selects the optimal ℓ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> -order one over the samples of a single pulse. We derive the error probability both under additive white Gaussian noise, for which a closed-form expression is obtained, and under the IEEE 802.15.4a channel model. We also conduct extensive simulations and show that the proposed solution significantly outperforms both single peak and energy detection UWB receivers in the presence of impulse noise.
Fast and Adaptive Color-to-Grayscale Conversion (sketches 0223) (2005)

Despite the widespread availability of color cameras and color displays, there is still a demand for black-and-white imagery due to three main factors: (1) artistic effects (e.g. Ansel Adams), (2) the cost gap between color and black-and-white printing, and (3) the design of many algorithms in image processing and computer vision that require a single value per pixel. Recent research [Rasche et al. 2005; Gooch et al. 2005] has focused on constraining the mapping of colors to grayscale values based on an image’s color content to produce good results with few parameters. Both groups tried to preserve the original distances between colors after they have been mapped to grayscale values.
CMOS compatible many-core noc architectures with multi-channel millimeter-wave wireless links (2012)

Traditional many-core designs based on the Network-on-Chip (NoC) paradigm suffer from high latency and power dissipation as the system size scales up due to their inherent multi-hop communication. NoC performance can be significantly enhanced by introducing long-range, low power, and high-bandwidth single-hop wireless links between far apart cores. This paper presents a design methodology and performance evaluation for a hierarchical small-world NoC with CMOS compatible on-chip millimeter (mm)-wave wireless long-range communication links. The proposed wireless NoC offers significantly higher bandwidth and lower energy dissipation compared to its conventional non-hierarchical wired counterpart in presence of both uniform and non-uniform traffic patterns. The performance improvement is achieved through efficient data routing and optimum placement of wireless hubs. Multiple wireless shortcuts operating simultaneously provide an energy efficient solution for design of many-core communication infrastructures.
Plasmonic nanoprobes: from chemical sensing to medical diagnostics and therapy (2013)

This article provides an overview of the development and applications of plasmonics-active nanoprobes in our laboratory for chemical sensing, medical diagnostics and therapy. Molecular Sentinel nanoprobes provide a unique tool for DNA/RNA biomarker detection both in a homogeneous solution or on a chip platform for medical diagnostics. The possibility of combining spectral selectivity and high sensitivity of the surface-enhanced Raman scattering (SERS) process with the inherent molecular specificity of nanoprobes provides an important multiplex diagnostic modality. Gold nanostars can provide an excellent multi-modality platform, combining two-photon luminescence with photothermal therapy as well as Raman imaging with photodynamic therapy. Several examples of optical detection using SERS and photonics-based treatments are presented to illustrate the usefulness and potential of the plasmonic nanoprobes for theranostics, which seamlessly combines diagnostics and therapy.
Inverse Problem of Phase Distribution Identification using Intensity Images (2006)

The optical phase distribution measurement is an important technology for many industrial applications. However, it requires a high precision measurement instrument which usually is expensive, delicate and requires laborious maintenance care. In this study, a new method which reconstructs optical phase distribution from intensity images has been developed. This method enables simple phase distribution measurement without expensive optical equipments and installation space. Firstly, the light is differently modulated by some optical systems, and intensity images of modulated light are measured by CCD camera. An inverse problem which reconstructs the phase distribution from the proposed measurement system is set up. This inverse problem is reduced to an unconstrained optimization problem which can be solved with non-linear optimization method such as BFGS method. The ill-posedness of the problem was overcome with regularization using a priori information whose unknown phase distribution is smooth. The effectiveness of the proposed method was demonstrated through some numerical simulation.
The growth kinetics study of CVD Cu on TiN barriers (2001)

Chemical vapor deposition of copper films on barrier metals, such as TiN and TaN has been intensively studied since the early 1990's. In contrast to active research on precursors, adhesion, and trench/via filling, the study of the initial growth of copper on barrier films has been rarely conducted. In this paper, the early growth stage of copper films on a titanium nitride coated substrate is fully studied. Two types of nucleation processes, homogeneous and heterogeneous, were observed under well controllable deposition conditions and were characterized through SEM, surface optical reflectance, and SIMS. The kinetics for each growth stage was also studied. The relationship between adhesion and initial nucleation is also discussed.
The capacity-coverage tradeoff in CDMA systems with soft handoff (2002)

In Veeravalli and Sendonaris (1997), the tradeoff between coverage and number of users was explicitly characterized for systems without soft handoff. It is well known that CDMA soft handoff can result in gains both in coverage and in number of users supported. In this paper we extend the analysis of Veeravalli and Sendonaris to derive analytical expressions that quantify the gains from soft handoff. Our analysis may be used in cellular planning in the following two ways: first, to calculate the coverage of cells based on the amount of traffic they will support; and second, to set hard limits on the number of users admitted into the cell in order to meet coverage requirements.
Hanging core support system for a nuclear reactor. [LMFBR] (1984)

For holding the reactor core in the confining reactor vessel, a support is disclosed that is structurally independent of the vessel, that is dimensionally accurate and stable, and that comprises tandem tension linkages that act redundantly of one another to maintain stabilized core support even in the unlikely event of the complete failure of one of the linkages. The core support has a mounting platform for the reactor core, and unitary structure including a flange overlying the top edge of the reactor vessels, and a skirt and box beams between the flange and platform for establishing one of the linkages. A plurality of tension rods connect between the deck closing the reactor vessel and the platform for establishing the redundant linkage. Loaded Belleville springs flexibly hold the tension rods at the deck and separable bayonet-type connections hold the tension rods at the platform.
Radiofrequency circuit design and performance evaluation for small animal frequency-domain NIR fluorescence optical tomography (2011)

Herein we report on hardware development and evaluation for frequency-domain photon migration (FDPM) technique that is miniaturized for incorporation into a micro-CT gantry for hybrid CT/NIR/PET imaging. Immunity to endogenous optical properties and enhanced contrast associated with fluorophore lifetime is inherent to the FDPM measurements and enables unique opportunities for quantitative tomography when compared to the time independent (continuous wave) approach. A miniaturized radiofrequency (<i>rf</i>) circuitry has been developed in our laboratory for homodyne FDPM measurements that makes use of a single 100MHz oscillator to simultaneously launch optically modulated excitation light into a small animal as well as to modulate an NIR sensitive image intensifier for collection of fluorescent signals. The use of a single oscillator not only eliminates signal drift that otherwise results from the use of multiple oscillators individually driving both source and detector, but also reduces the circuit footprint for incorporation into the CT gantry. Herein, overall system performance parameters of signal-to-noise ratio, measurement precision, spatial resolution, modulation depth (ac/dc), excitation light rejection, and clinically relevant data acquisition times are presented for mouse phantom data. Image reconstruction of phantom data and integration of circuitry for hybrid CT/NIR/PET imaging is also presented towards the ultimate validation of NIR optical tomography using PET imaging as a "gold-standard" for quantification.
Civilian GPS Spoofing Detection based on DualReceiver Correlation of Military Signals (2018)

Cross-correlations of unknown encrypted signals between\ntwo civilian GNSS receivers are used to detect spoofing\nof known open-source signals. This type of detection\nalgorithm is the strongest known defense against\nsophisticated spoofing attacks if the defended receiver has\nonly one antenna. The attack strategy of concern starts by\noverlaying false GNSS radio-navigation signals exactly\non top of the true signals. The false signals increase in\npower, lift the receiver tracking loops off of the true\nsignals, and then drag the tracking loops and the\nnavigation solution to erroneous, but consistent results.\nThis paper develops codeless and semi-codeless spoofing\ndetection methods for use in inexpensive, narrow-band\ncivilian GNSS receivers. Detailed algorithms and\nanalyses are developed that use the encrypted military\nP(Y) code on the L1 GPS frequency in order to defend\nthe open-source civilian C/A code. The new detection\ntechniques are similar to methods used in civilian dualfrequency\nGPS receivers to track the P(Y) code on L2 by\ncross-correlating it with P(Y) on L1. Successful detection\nof actual spoofing attacks is demonstrated by off-line\nprocessing of digitally recorded RF data. The codeless\ntechnique can detect attacks using 1.2 sec of correlation,\nand the semi-codeless technique requires correlation\nintervals of 0.2 sec or less. This technique has been\ndemonstrated in a narrow-band receiver with a 2.5 MHz\nbandwidth RF front-end that attenuates the P(Y) code by\n5.5 dB.
3D microfluidic <i>ex vivo</i> culture of organotypic tumor spheroids to model immune checkpoint blockade (2018)

Microfluidic culture has the potential to revolutionize cancer diagnosis and therapy. Indeed, several microdevices are being developed specifically for clinical use to test novel cancer therapeutics. To be effective, these platforms need to replicate the continuous interactions that exist between tumor cells and non-tumor cell elements of the tumor microenvironment through direct cell-cell or cell-matrix contact or by the secretion of signaling factors such as cytokines, chemokines and growth factors. Given the challenges of personalized or precision cancer therapy, especially with the advent of novel immunotherapies, a critical need exists for more sophisticated ex vivo diagnostic systems that recapitulate patient-specific tumor biology with the potential to predict response to immune-based therapies in real-time. Here, we present details of a method to screen for the response of patient tumors to immune checkpoint blockade therapy, first reported in Jenkins et al. Cancer Discovery, 2018, 8, 196-215, with updated evaluation of murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS), including evaluation of the requirement for 3D microfluidic culture in MDOTS, demonstration of immune-checkpoint sensitivity of PDOTS, and expanded evaluation of tumor-immune interactions using RNA-sequencing to infer changes in the tumor-immune microenvironment. We also examine some potential improvements to current systems and discuss the challenges in translating such diagnostic assays to the clinic.
Expression of Peripheral Benzodiazepine Receptor (PBR) in Human Tumors: Relationship to Breast, Colorectal, and Prostate Tumor Progression (2003)

High levels of peripheral-type benzodiazepine receptor (PBR), the alternative-binding site for diazepam, are part of the aggressive human breast cancer cell phenotype in vitro. We examined PBR levels and distribution in normal tissue and tumors from multiple cancer types by immunohistochemistry. Among normal breast tissues, fibroadenomas, primary and metastatic adenocarcinomas, there is a progressive increase in PBR levels parallel to the invasive and metastatic ability of the tumor (p < 0.0001). In colorectal and prostate carcinomas, PBR levels were also higher in tumor than in the corresponding non-tumoral tissues and benign lesions (p < 0.0001). In contrast, PBR was highly concentrated in normal adrenal cortical cells and hepatocytes, whereas in adrenocortical tumors and hepatomas PBR levels were decreased. Moreover, malignant skin tumors showed decreased PBR expression compared with normal skin. These results indicate that elevated PBR expression is not a common feature of aggressive tumors, but rather may be limited to certain cancers, such as those of breast, colon-rectum and prostate tissues, where elevated PBR expression is associated with tumor progression. Thus, we propose that PBR overexpression could serve as a novel prognostic indicator of an aggressive phenotype in breast, colorectal and prostate cancers.
New anisotropic conductive adhesives for low cost and reliable flip chip on organic substrates applications (2002)

Flip chip assembly on organic substrates using ACAs (anisotropic conductive adhesives) has advantages such as easier processing, good electrical performance, lower cost, green processes, and organic substrate-compatible low temperature processing. ACAs are composed of epoxy polymer resin and conductive fillers (less than 10 wt.%). ACAs thus have almost the same CTE values as epoxy alone, which are higher than conventional underfill materials with silica fillers. It is thus necessary to lower the ACA CTE value for more reliable flip chip assembly on organic substrates. New ACA composites with conductive and nonconductive fillers were devised. In this paper, we studied the effect of fillers on the thermo-mechanical properties of modified ACA composites and the reliability of flip chip assembly on organic substrates using modified ACAs and electroless Ni and Au stud bumps. As nonconducting filler content increased, CTE values decreased and storage modulus at room temperature increased. Contact resistance changes were measured during reliability tests such as thermal cycling, high humidity/temperature, and high temperature/dry test. It was noted that lowering ACA CTEs greatly enhanced thermal cycling reliability. Results also showed that flip chip assembly using modified ACAs with lower CTEs and higher modulus exhibited slightly better contact resistance behavior than conventional ACAs without nonconducting fillers. The greater reliability of flip chip on organic substrates using the new ACAs can lead to new low cost flip chip on organic substrate applications such as smart cards, RF, memory devices, etc.
Prospective validation of a serum miRNA panel for early detection of gastric cancer. (2019)

4065 Background: High mortality from gastric cancer is related to the late manifestation of its symptoms. A blood-based non-invasive biomarker with the ability to detect all stages of gastric cancer could significantly improve patient outcomes. We aimed to develop a novel serum miRNA assay for diagnosis of gastric cancer. Methods: We conducted a multi-center study involving 892 gastric cancer and control subjects from Singapore and Korea to develop a multi-target miRNA assay. Using RT-qPCR, we quantified the expressions of 578 serum miRNAs and constructed a 12-miR biomarker panel through multi-variant data analysis. The results were generated with the use of a logistic-regression algorithm, with the value of 40 or more considered to be positive. We subsequently validated this multi-miR assay in a large prospective cohort involving 4566 subjects and compared its performance with traditional markers such as H.Pylori and Pepsinogen. All participants underwent gastroscopy independent of the assay results. Results: Of the 4566 subjects that underwent gastroscopy and histopathological examination in the prospective cohort, 125 were diagnosed with gastric cancer. The 12-miR assay achieved an Area-Under-Curve (AUC) of 0.84, significantly outperforming (p-value < 0.01) that of H.Pylori (AUC of 0.64) and Pepsinogen (AUC of 0.62). The sensitivity of the miRNA assay in detecting early (stage 0-2) and late (stage 3-4) stage gastric cancer was 82.6% (95% CI, 68.6% to 92.2%) and 88.4% (95% CI, 78.4% to 94.9%) respectively at a specificity of 70.0% (95% CI, 67.8% to 71.9%). In comparison, H.Pylori showed a sensitivity of 80.4% at a specificity of 44.3% whereas the Pepsinogen showed sensitivity of 9.52% at a specificity of 95.3%. Using the miRNA assay as a pre-screening tool could potentially reduce number of endoscopy needed by 62% in detecting one case of gastric cancer. Conclusions: Our serum miRNA panel is a useful, non-invasive screening test for gastric cancer. It is cost-effective as it can reduce unnecessary diagnostic endoscopy.
Ytterbium-doped apatite-structure crystals: A new class of laser materials (1994)

A new class of Yb-lasers is summarized in this article. The apatite family of crystals, based on the hexagonal structure of the mineral fluorapatite, has been found to impose favorable spectroscopic and laser properties on the Yb3+ activator ion. Crystals of Yb-doped Ca5(PO4)3F, Sr5(PO4)3F, CaxSr5−x(PO4)3F, and Sr5(VO4)3F have been grown and investigated. Several useful laser crystals have been identified which offer a variety of fundamental laser parameters for designing diode-pumped systems. In general, this class of materials is characterized by high emission cross sections (3.6–13.1×10−20 cm2), useful emission lifetimes (0.59–1.26 ms), a strong pump band (σabs=2.0–10.0×10−20 cm2), and pump and extraction wavelengths near 900 and 1045 nm, respectively. Efficient lasing has been demonstrated for several of the members of this class of materials, and high optical quality crystals have been grown by the Czochralski method. A summary of the laser parameters and a discussion of the Yb:apatite class of lasers is presented.
β‐Arrestin 2 dependence of δ opioid receptor agonists is correlated with alcohol intake (2015)

Our finding that δ receptor agonists that strongly recruit β-arrestin 2 can increase alcohol intake carries important ramifications for drug development of δ receptor agonists for treatment of alcohol use disorders and depressive disorders.