gebhart/patrepeval huggingface dataset:
Efficient Hepatitis C Virus Genotype 1b Core-NS5A Recombinants Permit Efficacy Testing of Protease and NS5A Inhibitors (2017)

Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants, permitted by the high replication capacity of strain JFH1 (genotype 2a), has advanced efficacy and resistance testing of antivirals. However, efficient infectious JFH1-based cell cultures of subtype 1b are limited and comprise only the 5' untranslated region (5'UTR)-NS2, NS4A, or NS5A regions. Importantly, it has not been possible to develop efficient 1b infectious systems expressing the NS3/4A protease, an important target of direct-acting antivirals. We developed efficient infectious JFH1-based cultures with genotype 1b core-NS5A sequences of strains DH1, Con1, and J4 by using previously identified HCV cell culture adaptive substitutions A1226G, R1496L, and Q1773H. These viruses spread efficiently in Huh7.5 cells by acquiring additional adaptive substitutions, and final recombinants yielded peak supernatant infectivity titers of 4 to 5 log<sub>10</sub> focus-forming units (FFU)/ml. We subsequently succeeded in adapting a JFH1-based 5'UTR-NS5A DH1 recombinant to efficient growth in cell culture. We evaluated the efficacy of clinically relevant NS3/4A protease and NS5A inhibitors against the novel genotype 1b viruses, as well as against previously developed 1a viruses. The inhibitors were efficient against all tested genotype 1 viruses, with NS5A inhibitors showing half-maximal effective concentrations several orders of magnitude lower than NS3/4A protease inhibitors. In summary, the developed HCV genotype 1b culture systems represent valuable tools for assessing the efficacy of various classes of antivirals and for other virological studies requiring genotype 1b infectious viruses.
<title>Particle imaging technique for size, velocity, and concentration measurements in particle-laden flows</title> (1997)

Particle laden flows are encountered in many fossil fuel and industrial processes such as the gas-solid flows in power plants, liquid-solid flows in coal and grain transportation and gas-liquid flows in combustors. These flows are not well understood, thus computational fluid dynamic modeling of these system has been hampered. Fundamental measurements are required to study the motion of the different phases to obtain an understanding of these flows and to develop reliable models. No reliable non-intrusive methods are available to fully characterize two phase flow fields, i.e. obtain particle size, velocity, concentration and concentration gradients at the same time over an extended area of interest. Intrusive sampling methods compromise the two phase flow field making the measurements suspect. Conventional optical methods do not disturb the flow but provide local point wise velocity measurements only. Particle size can be obtained for only spherical particles using the phase Doppler interferometric methods.
Functionalized congener approach to muscarinic antagonists: analogs of pirenzepine (1991)

The M1-selective muscarinic receptor antagonist pirenzepine 6H-pyrido[2,3-b][1,4]benzodiazepin-6-one) was derivatized to explore points of attachment of functionalized side chains for the synthesis of receptor probes and ligands for affinity chromatography. The analogues prepared were evaluated in competitive binding assays versus [3H]-N-methylscopolamine at four muscarinic receptor subtypes (m1AChR-m4AChR) in membranes from rat heart tissue and transfected A9L cells. 9-(Hydroxymethyl)pirenzepine, 8-(methylthio)pirenzepine, and a series of 8-aminosulfonyl derivatives were synthesized. Several 5-substituted analogues of pirenzepine also were prepared. An alternate series of analogues substituted on the 4-position of the piperazine ring was prepared by reaction of 4-desmethylpirenzepine with various electrophiles. An N-chloroethyl analogue of pirenzepine was shown to form a reactive aziridine species in aqueous buffer yet failed to affinity label muscarinic receptors. Within a series of aminoalkyl analogues, the affinity increased as the length of the alkyl chain increased. Shorter chain analogues were generally much less potent than pirenzepine, and longer analogues (7-10 carbons) were roughly as potent as pirenzepine at m1 receptors, but were nonselective. Depending on the methylene chain length, acylation or alkyl substitution of the terminal amine also influenced the affinity at muscarinic receptors.
Electronic portal imaging based on Cerenkov radiation: A new approach and its feasibility (2006)

Most electronic portal imaging devices (EPIDs) developed so far use a Cu plate/phosphor screen to absorb x rays and convert their energies into light, and the light image is then read out. The main problem with this approach is that the Cu plate/phosphor screen must be thin (approximately 2 mm thick) in order to obtain a high spatial resolution, resulting in a low x-ray absorption or low quantum efficiency for megavoltage x rays (typically 2-4%). In addition, the phosphor screen contains high atomic number (high-Z) materials, resulting in an over-response of the detector to low-energy x rays in dosimetric verification. In this paper, we propose a new approach that uses Cerenkov radiation to convert x-ray energy absorbed by the detector into light for portal imaging applications. With our approach, a thick (approximately 10-30 cm) energy conversion layer made of a low-Z dielectric medium, such as a large-area, thick fiber-optic taper consisting of a matrix of optical fibers aligned with the incident x rays, is used to replace the thin Cu plate/phosphor screen. The feasibility of this approach has been investigated using a single optical fiber embedded in a solid material. The spatial resolution expressed by the modulation transfer function (MTF) and the sensitivity of the detector at low doses (approximately one Linac pulse) have been measured. It is predicted that, using this approach, a detective quantum efficiency of an order of magnitude higher at zero frequency can be obtained while maintaining a reasonable MTF, as compared to current EPIDs.
Deterministic and Stochastic Trajectories of Magnetic Particles: Mapping Energy Landscapes for Technology And Biology (2014)

Technologies that control matter at the nano- and micro-scale are crucial to realizing engineered systems that can assemble, transport, and manipulate materials at submicron length scales. Two principles: (1) the domain wall structure of patterned magnetic structures and (2) the superparamagnetic properties of nanoparticles, have been previously used to remotely manipulate and transport magnetic entities to specific sites on a platform. In this paper, changes to the energy landscape during transport as well as the local energy profile of individual stationary traps, both of which are central to the functionality of the platform, are evaluated using directed forces and stochastic (Brownian) trajectories of trap-confined microparticles. Hybrid magnetic-fluorescent micelle nanoconstructs, which are compatible with physiological conditions and safeguard functionality of biomaterials, are shown to be viable markers to label and manipulate individual cells across the platform.
Novel macrolides through genetic engineering (1999)

Erythromycin, a complex polyketide antibiotic belonging to the macrolide class, is produced as a natural product by the bacterium Saccharopolyspora erythraea. The genes encoding the enzymes responsible for the synthesis of the antibiotic have been cloned and sequenced, revealing that the polyketide backbone of the molecule in produced by a polyketide synthase (PKS) composed of multifunctional proteins that contain discrete functional domains for each step of synthesis. Genetic manipulation of the PKS-encoding genes can result in predictable changes in the structure of the polyketide component of erythromycin, many of which are not easily achievable through standard chemical derivatization or synthesis. Many of the changes can be combined to lead to the further generation of navel structures. Whereas genetic engineering of the erythromycin structure has been practiced for a number of years, the re cent and continuing discoveries of modular PKSs for the synthesis of many other important complex polyketides has raised the possibility of generating novel structures in these molecules by genetic manipulation, as well.
Stabilization of dried coal. [as mined lignite or bituminous coal is mixed with hot dried coal] (1977)

A process for stabilizing lignitic and sub-bituminous coal against spontaneous combustion is comprised of mixing as-mined lignitic or sub-bituminous coal with said hot, completely or partially dried lignitic or sub-bituminous coal in an amount to produce a weight ratio of dried coal to as-mined coal from about 1 : 2 to about 10 : 1.
Internal Wire Guide For Gas/Tungsten-Arc Welding (1990)

Wire kept in shielding gas, preventing oxidation. Guide inside gas cup of gas/tungsten-arc welding torch feeds filler wire to weld pool along line parallel to axis of torch. Eliminates problem of how to place and orient torch to provide clearance for external wire guide.
Evolutionary programming for training neural networks (1990)

The use of evolutionary programming to train a neural network is addressed by examining a simple classification problem involving two populations of interest. The first follows a Gaussian distribution having zero means and unit variance; the second is also Gaussian, but with a mean of one and unit variance. Ten independent samples are drawn from either one of the populations with the objective being to properly identify the appropriate underlying distribution. A network consisting of 10 input nodes, a single hidden layer of 10 nodes, and a final classifying node was constructed. To train the network, evolutionary programming was used to minimize the sum of the squared differences between each target output and the actual network output. A population of 10 parent vectors representing the 121 weights and biases of the network was maintained, and the limit of evolution was chosen to be 1000 generations. A training set of 100 patterns, 50 from each population, was determined randomly and then fixed for the extent of the evolution. The results indicate that evolutionary programming is useful for discovering the optimal set of weights in a neural network
Formation of Copper Nanowires by Electroless Deposition Using Microtubules as Templates (2008)

Microtubules (MTs) are self-assembling, protein-based, tubular structures several micrometers long with outer and inner diameters of 25 nm and 15 nm, respectively. This aspect ratio makes MTs ideal templates for producing nanowires for applications such as electrical nano-interconnects. MTs are poorly conductive and their use as interconnects necessitates their metallization. We report a process for metallization of MTs with copper using a biologically benign electroless deposition chemistry consisting of copper sulfate solution containing acetic acid as a complexant and ascorbic acid as reducing agent. The pH of the plating bath is controlled such that copper metallization occurs without disassembling the MTs. Electron microscopic characterization of the morphology and dimensions of the copper nanowires shows that metallization for approximately 1 minute produces a uniform nanowire with an average diameter of approximately 15 nm, suggesting that metallization is initiated selectively from the MT inner core.
Data-Driven Activity Prediction (2015)

We consider a novel problem called Activity Prediction, where the goal is to predict the future activity occurrence times from sensor data. In this paper, we make three main contributions. First, we formulate and solve the activity prediction problem in the framework of imitation learning and reduce it to simple regression learning problem. This approach allows us to leverage powerful regression learners; is easy to implement; and can reason about the relational and temporal structure of the problem with negligible computational overhead. Second, we present several evaluation metrics to evaluate a given activity predictor, and discuss their pros and cons in the context of real-world applications. Third, we evaluate our approach using real sensor data collected from 24 smart home testbeds. We also embed the learned predictor into a mobile device based activity prompter and evaluate the app on multiple participants living in smart homes. Our experimental results indicate that the activity predictor learned with our approach performs better than the baseline methods, and offers a simple and reliable approach to prediction of activities from sensor data.
On the Difficulties of Disclosure Prevention in Statistical Databases or The Case for Differential Privacy (2010)

In 1977 Tore Dalenius articulated a desideratum for statistical databases: nothing about an individual should be learnable from the database that cannot be learned without access to the database. We give a general impossibility result showing that a natural formalization of Dalenius’ goal cannot be achieved if the database is useful. The key obstacle is the side information that may be available to an adversary. Our results hold under very general conditions regarding the database, the notion of privacy violation, and the notion of utility. Contrary to intuition, a variant of the result threatens the privacy even of someone not in the database. This state of affairs motivated the notion of differential privacy [15, 16], a strong ad omnia privacy which, intuitively, captures the increased risk to one’s privacy incurred by participating in a database.
Single atom changes in newly synthesized HIV protease inhibitors reveal structural basis for extreme affinity, high genetic barrier, and adaptation to the HIV protease plasticity (2020)

HIV-1 protease inhibitors (PIs), such as darunavir (DRV), are the key component of antiretroviral therapy. However, HIV-1 often acquires resistance to PIs. Here, seven novel PIs were synthesized, by introducing single atom changes such as an exchange of a sulfur to an oxygen, scission of a single bond in P2'-cyclopropylaminobenzothiazole (or -oxazole), and/or P1-benzene ring with fluorine scan of mono- or bis-fluorine atoms around DRV's scaffold. X-ray structural analyses of the PIs complexed with wild-type Protease (PR<sub>WT</sub>) and highly-multi-PI-resistance-associated PR<sub>DRV</sub><sup>R</sup><sub>P51</sub> revealed that the PIs better adapt to structural plasticity in PR with resistance-associated amino acid substitutions by formation of optimal sulfur bond and adaptation of cyclopropyl ring in the S2'-subsite. Furthermore, these PIs displayed increased cell permeability and extreme anti-HIV-1 potency compared to DRV. Our work provides the basis for developing novel PIs with high potency against PI-resistant HIV-1 variants with a high genetic barrier.
A New Michael-Reaction-Resistant Benzoquinone for Aqueous Organic Redox Flow Batteries (2017)

We report here the synthesis, characterization and properties of 3,6-dihydroxy-2,4-dimethylbenzenesulfonic acid (DHDMBS) as a new positive side electrolyte material for aqueous organic redox flow batteries (ORBAT). We have synthesized this material in pure form in high yield and confirmed its structure. We have determined that the standard reduction potential, the rate constant of the redox reaction, and the diffusion coefficient are ideally suited for use in ORBAT. Specifically, DHDMBS overcomes the major issue of Michael reaction with water faced with 4,5-dihydroxybenzene-1,3-disulfonic acid (BQDS) and similar unsubstituted benzoquinones in the selection of positive electrolyte materials. DHDMBS can be synthesized relatively inexpensively. We have demonstrated the chemical stability of DHDMBS to repeated electrochemical cycling through NMR and electrochemical studies proving the absence of products of the Michael reaction. A flow cell with DHDMBS and anthraquinone-2,7-disulfonic acid has now been shown to operate close to 100% coulombic efficiency for over 25 cycles when continuously cycled at 100 mA/cm2, and can sustain current densities as high as 500 mA/cm2 without noticeable chemical degradation. However, there was a slow decrease in the capacity of the flow cell attributable to the crossover of DHDMBS from the positive side of the cell. Thus, the present study has shown DHDMBS as a promising candidate for the positive side material for an all-organic aqueous redox flow battery in acidic media, and our future efforts will focus on understanding the crossover of DHDMBS and the effects of long-term cycling.
Design and fabrication of a novel SAW bio/chemical sensor in CMOS (2005)

The design, fabrication, post-processing and characterization of a novel SAW (Surface Acoustic Wave) based bio/chemical sensor in CMOS technology is introduced. The sensors are designed in AMI 1.5 mum 2 metal, 2 poly process. A unique maskless post processing sequence is designed and completed. The three post-processing steps are fully compatible with any CMOS technology. This allows any signal control/processing circuitry to be easily integrated on the same chip. ZnO is used as the piezoelectric material for the SAW generation. A thorough characterization and patterning optimization of the sputtered ZnO was carried out. The major novelties that are introduced in the SAW delay line features are: The embedded heater elements for temperature control, compensation and acoustic absorbers that are designed to eliminate edge reflections and minimize triple transit interference. Both of these attributes are designed by using the CMOS layers without disturbing the SAW performance
Elucidating Raman Image-Guided Differential Recognition of Clinically Confirmed Grades of Cervical Exfoliated Cells by Dual Biomarker-Appended SERS-Tag (2021)

Ultrasensitive detection of cancer biomarkers via single-cell analysis through Raman imaging is an impending approach that modulates the possibility of early diagnosis. Cervical cancer is one such type that can be monitored for a sufficiently long period toward invasive cancer phenotype. Herein, we report a surface-enhanced Raman scattering (SERS) nanotag (SERS-tag) for the simultaneous detection of p16/K-i67, a dual biomarker persisting in the progression of squamous cell carcinoma of human cervix. A nanoflower-shaped SERS-tag, constituted of hybrid gold nanostar with silver tips to achieve maximum fingerprint enhancement from the incorporated reporter molecule, was further functionalized with the cocktail monoclonal antibodies against p16/K-i67. The recognition by the SERS-tag was first validated in cervical squamous cell carcinoma cell line SiHa as a foot-step study and subsequently implemented to different grades of clinically confirmed exfoliated cells including normal cell (NC), high-grade intra-epithelial lesion (HC), and squamous cell carcinoma (CC) samples of the cervix. Precise Raman mapped images were constituted based on the average intensity gradient of the signature Raman peaks arising from different grades of exfoliated cells. We observed a distinct intensity hike of around 10-fold in the single dysplastic HC and CC samples in comparison to NC specimen, which clearly justify the prevalence of p16/Ki-67. The synthesized probe is able to map the abnormal cells within 20 min with high reproducibility and stability for 1 mm × 1 mm mapping area with good contrast. Amidst the challenges in Raman image-guided modality, the technique was further complemented with the gold standard immunocytochemistry (ICC) dual staining analysis. Even though both are time-consuming techniques, tedious steps can be avoided and real-time readout can be achieved using the SERS mapping unlike immunocytochemistry technique. Therefore, the newly developed Raman image-guided SERS imaging emphasizes the approach of uplifting of SERS in practical utility with further improvement for clinical applications for cervical cancer detection in future.
Excitation of broadband surface plasmon polaritons: Plasmonic continuum spectroscopy (2005)

The excitation of surface plasmon polaritons in a thin metal film is extremely sensitive to the surrounding dielectric environment. We introduce here a far-field method to directly observe surface plasmon propagation and demonstrate that the lateral intensity decay length is affected by a change of the interface properties. The method relies on the detection of the intrinsic lossy modes associated with plasmon propagation in thin films. We also introduce a method to excite a broad spectral distribution of surface plasmons simultaneously throughout the visible spectrum allowing a unique form of surface plasmon-based spectroscopy.
Electromagnetic method for locating underground anomalies (1977)

Underground anomalies or discontinuities, such as holes, tunnels, and caverns, are located by lowering an electromagnetic signal transmitting antenna down one borehole and a receiving antenna down another, the ground to be surveyed for anomalies being situated between the boreholes. Electronic transmitting and receiving equipment associated with the antennas is activated and the antennas are lowered in unison at the same rate down their respective boreholes a plurality of times, each time with the receiving antenna at a different level with respect to the transmitting antenna. The transmitted electromagnetic waves diffract at each edge of an anomaly. This causes minimal signal reception at the receiving antenna. Triangulation of the straight lines between the antennas for the depths at which the signal minimums are detected precisely locates the anomaly. Alternatively, phase shifts of the transmitted waves may be detected to locate an anomaly, the phase shift being distinctive for the waves directed at the anomaly.
Wideband Tunable Dispersion Compensator Using a 25-Stage PLC-MZI (2009)

In high-bit-rate optical transmission systems that are being introduced into commercial applications, such as those with 40-Gbps bit-rate, there is a need for tunable dispersion compensators (TDCs) that enable adaptive compensation for dispersion fluctuations due to temperature changes and the like in the transmission lines, and accordingly, a variety of TDCs based on different principles have been reported. In particular, the cascaded Mach-Zehnder interferometer (MZI) type TDC using a lattice type filter based on the silica-based planar lightwave circuit (PLC) technology is promising because of its ease of control and large achievable dispersion. However, the usable bandwidths of this type of TDCs reported to date are thought to be insufficient for their practical application to the 40-Gbps systems. We have demonstrated here, therefore, a TDC using a 25-stage PLC-MZI that combines a usable bandwidth of 60 GHz or higher and a tunable dispersion range of ±300 ps/nm or more. Its superior characteristics will be reported in this paper. ABSTRACT * FITEL-Photonics Lab., R&D Div.