gebhart/patrepeval huggingface dataset:
A portable battery powered electrochemical detection circuit with a 1000 volt CE power supply for microchip capillaries (2002)

Capillary electrophoresis (CE) with electrochemical detection (ECD) is an attractive combination for a miniaturized portable instrument. Capillaries and integrated detection electrodes can be fabricated accurately and at low cost using microfabrication processes. Precise sample injection and electrode alignment issues are addressed via interconnecting capillaries and patterned electrodes respectively. However, to fully realize the portability offered by microfabricated devices, a portable battery powered ECD circuit and HV CE power supply is developed. The ECD circuit and HV CE power supply are each constructed on 3"/spl times/4" PCBs including batteries. The detection circuit has adjustable gain, applied electrode voltage, and current offset. The CE power supply contains one positive and one negative voltage source. Each voltage source is filtered, regulated, adjustable from 250 VDC to 1 kVDC, and can source up to 400 /spl mu/A. Both the power supply and detection circuit are connected to a portable computer using LabView software for control and data acquisition. A capillary biasing method using the negative voltage source for injection and the positive voltage source for separation is also presented. This method simplifies detection and capillary current measurement circuits and requires minimal interface circuitry. The CE power supply performance is evaluated with electrical tests and a laser induced fluorescence (LIF) experiment. The detection circuit is tested by performing dopamine and catechol ECD experiments. Results show the successful injection, separation, and electrochemical detection of analytes using microchip capillaries.
Threshold modulation in error diffusion (1993)

A theoretical analysis of threshold modulation in error diffusion is given. It is shown that spatial modulation of the threshold is mathematically identical to processing an equivalent input image with the standard error diffusion algorithm. The equivalent input is the sum of the original image with a high-pass-filtered version of the threshold spatial modulation. The filter is a function only of the weights used to distribute the errors. This result can be used to explain the several published observed effects of threshold modulation, such as edge enhancement and the effects of adding noise to the threshold.
Bicell pyroelectric optical detector made from a single LiNbO_3 domain-reversed electret (1998)

Using electric-field poling at room temperature, we selectively reversed the direction of the spontaneous polarization in a 200-mum-thick, z-cut LiNbO(3) electret to produce a bicell pyroelectric detector. The detector required only a single set of electrodes, one electrode on the front surface and one on the back surface. Microphonic noise that is typical of monocell pyroelectric detectors is reduced in the present device. Our spatial uniformity data indicate that the optical response of one half of the bicell detector area was equal to and opposite the other half within 1.2%. The microphonic suppression of the bicell pyroelectric detector was less than -36 dB from 10 to 50 Hz and less than -118 dB at 35 Hz of that of a reference monocell pyroelectric detector. The substrate thickness is significantly greater than those of other domain-engineered pyroelectric detector designs and allows us to build practical, large-area detectors for radiometric applications.
<title>Wavelet detection of clustered microcalcifications</title> (1996)

An automated method for detecting microcalcification clusters is presented. The algorithm begins with a digitized mammogram and outputs the center coordinates of regions of interest (ROIs). The method presented uses a non-linear function and a 12-tap least asymmetric Daubechies (LAD12) wavelet in a tree structured filter bank to increase the signal to noise level by 10.26 dB. The signal to noise level gain achieved by the filtering allows subsequent thresholding to eliminate on average 90% of the image from further consideration without eliminating actual microcalcification clusters 95% of the time. Morphological filtering and texture analysis are then used to identify individual microcalcifications. Altogether, the method successfully detected 44 of 53 microcalcification clusters (83%) with an average of 2.3 false positive clusters per image. A cluster is considered detected if it contains 3 or more microcalcifications within a 6.4 mm by 6.4 mm area. The method successfully detected 13 of the 14 malignant cases (93%).
Abstract 3915: Tumor-targeted hyaluronan (HA) imaging with a recombinant HA binding protein: TSG6dHep-Fc. (2013)

Abstract A new investigational therapeutic agent, pegylated recombinant human hyaluronidase PH20 (PEGPH20) is a currently under clinical development for the treatment of tumors that accumulate hyaluronan (HA), a nonsulfated glycosaminoglycan and a major constituent of the extracellular matrix (ECM) of many solid tumors. HA accumulation has been correlated with local invasion, the presence of distal metastasis, higher tumor grade, and poorer overall survival in multiple malignancies. Preclinical studies have demonstrated that sustained HA removal, accomplished with PEGPH20, inhibits tumor growth and enhances chemotherapeutic activity in HA-rich xenografts and genetically engineered mouse tumor models. To facilitate non-invasive clinical selection of patients with HA-rich malignancies, and confirm PEGPH20 enzymatic targeting of these malignancies, we have developed a soluble recombinant HA binding protein by fusing a tumor necrosis factor-stimulated gene-6 protein (TSG6) fragment, mutated at the heparin-binding site, with human IgG1 Fc (TSG6dHep-Fc). In preclinical proof-of-concept studies, recombinant TSG6dHep-Fc was labeled with the near-infrared fluorophore DyLight755 (TSG6dHep-FcDL755) and administered IV to the following xenograft peritibial athymic mouse models: HA-rich pancreatic BxPC3, HA-poor prostate Du145 and HA-rich prostate Du145/HAS2. TSG6dHep-FcDL755 HA binding was imaged via fluorescence (IVIS Lumina II, Caliper Life Sciences, Inc.). Systemic/dermal HA binding was weakly present, but easily removed via background subtraction to allow tumor intensity quantification. In the HA-rich xenograft models, pancreatic BxPC3 and prostate Du145/HAS2, TSG6dHep-FcDL755 strongly labeled the peritibial tumors, peaking at 2 days post administration and was completely absent at day 10 post administration. In contrast, the HA-poor prostate Du145 tumors were very weakly labeled, making background subtraction of systemic/dermal HA binding difficult. In separate experiments, mice were treated with a single dose of PEGPH20 (4.5 mg/kg, IV) or vehicle prior to TSG6dHep-FcDL755 imaging. In all groups dosed with PEGPH20, TSG6dHep-FcDL755 signal intensity was extremely low and appeared to be limited to non-specific, whole body labeling. These results suggest that imaging with labeled TSG6dHep-Fc could be a useful tool for selecting patients with HA-rich malignancies, thereby enabling clinicians to noninvasively identify patients who might benefit from therapies that target HA and the ECM. Citation Format: Xiaoming Li, Lei Huang, Ge Wei, Ryan J. Osgood, Qiping Zhao, Ping Jiang, H. Michael Shepard, Daniel C. Maneval, Curtis B. Thompson. Tumor-targeted hyaluronan (HA) imaging with a recombinant HA binding protein: TSG6dHep-Fc. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3915. doi:10.1158/1538-7445.AM2013-3915
Oculometric assessment of visual motion processing (2014)

Eye movements are the most frequent (~3 per second), shortest-latency (~150-250 ms), and biomechanically simplest (1 joint, no inertial complexities) voluntary motor behavior in primates, providing a model system to assess sensorimotor disturbances arising from trauma, fatigue, aging, or disease states. We developed a 15-minute behavioral tracking protocol consisting of randomized step-ramp radial target motion to assess several aspects of the behavioral response to visual motion, including pursuit initiation, steady-state tracking, direction tuning, and speed tuning. Whereas our initiation and steady-state tracking metrics quantify the motor response, our direction and speed-tuning metrics can be converted into standard psychophysical thresholds. Methods. Observers were asked to pursue a small spot that made an initial step from fixation, then moved back through fixation in a Rashbass (1961) step-ramp design. De-saccaded eye-velocity responses were used to measure: pursuit latency and acceleration during initiation; gain, catch-up saccade amplitude, and proportion of smooth movements during steady-state tracking; direction-tuning anisotropy, asymmetry, and direction noise; and speed-tuning slope and noise. Variations on the step-ramp task were run to evaluate the test-retest repeatability and validity of our task, and to collect a baseline dataset from a population of 41 observers. Results. Our test-retest repeatability evaluation showed that initiation and steady-state tracking metrics were stable enough to allow individual differences to be measured (p<0.0001, Kruskal-Wallis). Our validity evaluation showed that initiation metrics show large decrements as the motion stimulus degrades with sampling (p<0.0001, ANOVA) and two of three steady-state tracking metrics show more subdued impairments (p<0.05, ANOVA). Conclusion. Our method delivers ten metrics that quantify pursuit and saccadic eye movements following a simple 15-minute clinical test, which may be useful as a screening tool for disorders affecting sensorimotor processing. Meeting abstract presented at VSS 2014
A Protein Phosphatase Methylesterase (PME-1) Is One of Several Novel Proteins Stably Associating with Two Inactive Mutants of Protein Phosphatase 2A (1999)

Carboxymethylation of proteins is a highly conserved means of regulation in eukaryotic cells. The protein phosphatase 2A (PP2A) catalytic (C) subunit is reversibly methylated at its carboxyl terminus by specific methyltransferase and methylesterase enzymes which have been purified, but not cloned. Carboxymethylation affects PP2A activity and varies during the cell cycle. Here, we report that substitution of glutamine for either of two putative active site histidines in the PP2A C subunit results in inactivation of PP2A and formation of stable complexes between PP2A and several cellular proteins. One of these cellular proteins, herein named protein phosphatase methylesterase-1 (PME-1), was purified and microsequenced, and its cDNA was cloned. PME-1 is conserved from yeast to human and contains a motif found in lipases having a catalytic triad-activated serine as their active site nucleophile. Bacterially expressed PME-1 demethylated PP2A C subunit in vitro, and okadaic acid, a known inhibitor of the PP2A methylesterase, inhibited this reaction. To our knowledge, PME-1 represents the first mammalian protein methylesterase to be cloned. Several lines of evidence indicate that, although there appears to be a role for C subunit carboxyl-terminal amino acids in PME-1 binding, amino acids other than those at the extreme carboxyl terminus of the C subunit also play an important role in PME-1 binding to a catalytically inactive mutant.
Precise and automated microfluidic sample preparation. (2004)

Autonomous bio-chemical agent detectors require sample preparation involving multiplex fluid control. We have developed a portable microfluidic pump array for metering sub-microliter volumes at flowrates of 1-100 {micro}L/min. Each pump is composed of an electrokinetic (EK) pump and high-voltage power supply with 15-Hz feedback from flow sensors. The combination of high pump fluid impedance and active control results in precise fluid metering with nanoliter accuracy. Automated sample preparation will be demonstrated by labeling proteins with fluorescamine and subsequent injection to a capillary gel electrophoresis (CGE) chip.
Speculative interference attacks: breaking invisible speculation schemes (2021)

Recent security vulnerabilities that target speculative execution (e.g., Spectre) present a significant challenge for processor design. These highly publicized vulnerabilities use speculative execution to learn victim secrets by changing the cache state. As a result, recent computer architecture research has focused on invisible speculation mechanisms that attempt to block changes in cache state due to speculative execution. Prior work has shown significant success in preventing Spectre and other attacks at modest performance costs. In this paper, we introduce speculative interference attacks, which show that prior invisible speculation mechanisms do not fully block speculation-based attacks that use cache state. We make two key observations. First, mis-speculated younger instructions can change the timing of older, bound-to-retire instructions, including memory operations. Second, changing the timing of a memory operation can change the order of that memory operation relative to other memory operations, resulting in persistent changes to the cache state. Using both of these observations, we demonstrate (among other attack variants) that secret information accessed by mis-speculated instructions can change the order of bound-to-retire loads. Load timing changes can therefore leave secret-dependent changes in the cache, even in the presence of invisible speculation mechanisms. We show that this problem is not easy to fix. Speculative interference converts timing changes to persistent cache-state changes, and timing is typically ignored by many cache-based defenses. We develop a framework to understand the attack and demonstrate concrete proof-of-concept attacks against invisible speculation mechanisms. We conclude with a discussion of security definitions that are sufficient to block the attacks, along with preliminary defense ideas based on those definitions.
A Study of the Feasibility of Steam-Augmented Gas Turbines for Surface Ships (1993)

The steam-augmented gas turbine (SAGT) has attracted attention because of its increased fuel efficiency. It yields significant, cost-effective increments of output power, particularly when steam/water injection is increased to levels approaching 50% of air flow. Such high levels of steam/water consumption permit burner operation near stoichiometric combustion ratios with specific powers exceeding 580 hp-sec/lb anticipated. This paper examines steam-augmented gas turbines for their applicability in Navy DDG-class ship environments. SAGT engine concepts exhibit efficiencies approaching the Navy’s intercooled regenerative (ICR) engine, and an impressive compactness that arises from the high specific power of steam. Polished water consumption may be 425,000 gal/day for a 100,000-hp SAGT-engine ship plant. Nevertheless, SAGT engine systems impose little if any negative ship impact even after accounting for water purification systems. Moreover, because of their high specific power, SAGT systems are as affordable, on a first-acquisition-cost basis, as the current gas turbine systems in the fleet, and in the present supply pipeline.
Modeling the Adenosine Receptors:  Comparison of the Binding Domains of A<sub>2A</sub>Agonists and Antagonists (2003)

A three-dimensional model of the human A(2A) adenosine receptor (AR) and its docked ligands was built by homology to rhodopsin and validated with site-directed mutagenesis and the synthesis of chemically complementary agonists. Different binding modes of A(2A)AR antagonists and agonists were compared by using the FlexiDock automated docking procedure, with manual adjustment. Putative binding regions for the 9H-purine ring in agonist NECA 3 and the 1H-[1,2,4]triazolo[1,5-c]quinazoline ring in antagonist CGS15943 1 overlapped, and the exocyclic amino groups of each were H-bonded to the side chain of N(6.55). For bound agonist, H-bonds formed between the ribose 3'- and 5'-substituents and the hydrophilic amino acids T(3.36), S(7.42), and H(7.43), and the terminal methyl group of the 5'-uronamide interacted with the hydrophobic side chain of F(6.44). Formation of the agonist complex destabilized the ground-state structure of the A(2A)AR, which was stabilized through a network of H-bonding and hydrophobic interactions in the transmembrane helical domain (TM) regions, facilitating a conformational change upon activation. Both flexibility of the ribose moiety, required for the movement of TM6, and its H-bonding to the receptor were important for agonism. Two sets of interhelical H-bonds involved residues conserved among ARs but not in rhodopsin: (1) E13(1.39) and H278(7.43) and (2) D52(2.50), with the highly conserved amino acids N280(7.45) and S281(7.46), and N284(7.49) with S91(3.39). Most of the amino acid residues lining the putative binding site(s) were conserved among the four AR subtypes. The A(2A)AR/3 complex showed a preference for an intermediate conformation about the glycosidic bond, unlike in the A(3)AR/3 complex, which featured an anti-conformation. Hydrophilic amino acids of TMs 3 and 7 (ribose-binding region) were replaced with anionic residues for enhanced binding to amine-derivatized agonists. We identified new neoceptor (T88D)-neoligand pairs that were consistent with the model.
The use of hybrid virus‐like particles to enhance the immunogenicity of a broadly protective HPV vaccine (2014)

Virus-like particles (VLPs) can serve as a highly immunogenic vaccine platform for the multivalent display of epitopes from pathogens. We have used bacteriophage VLPs to develop vaccines that target a highly conserved epitope from the human papillomavirus (HPV) minor capsid protein, L2.VLPs displaying an L2-peptide from HPV16 elicit antibodies that broadly neutralize infection by HPV types associated with the development of cervical cancer. To broaden the cross-neutralization further, we have developed a strategy to display two different peptides on a single, hybrid VLP in a multivalent, highly immunogenic fashion. In general, hybrid VLPs elicited high-titer antibody responses against both targets, although in one case we observed an immunodominant response against only one of the displayed epitopes. Immunization with hybrid particles elicited antibodies that were able to neutralize heterologous HPV types at higher titers than those elicited by particles displaying one epitope alone, indicating that the hybrid VLP approach may be an effective technique to target epitopes that undergo antigenic variation.
Interferometric Measurement Of In-Vivo Contact Lens Wetting (1989)

By observing the specular reflectance of monochromatic light from the anterior and posterior boundaries of the tear film on the front surface of a contact lens, optical conditions can be met which allow the observation of interference fringe patterns. Such patterns permit the thickness distribution of the pre-lens tear layer to be seen over a sizable area of the curved lens surface. Since the resulting interference pattern is analogous to a topographical map of the tear film thickness, but which is changing rapidly with time, continuous observation and recording of the patterns allow detailed information to be obtained concerning the time course and dynamics of tear film flow, thinning, and breakup during the interblink periods associated with normal blinking. With a contact lens of a given material, evaporation of the thin anterior tear layer was thought to be the major factor causing lens drying. Use of the tear film interferometer indicates that while this is usually the case for soft, hydrophilic lenses, both hard and rigid gas permeable (RGP) lenses have much shorter tear film breakup times largely independent of evaporative effects. The prelens tear fluid can be seen to be drawn off as a continuous sheet by the fluid in the tear menisci along the upper and lower lid margin due to surface tension differences, as long as continuity exists between the prelens tear film and either meniscus. This meniscus effect acts more rapidly than thinning by evaporation, and appears to be the primary factor determining the length of time hard or RGP lens surface will remain wet during interblink periods.
Generation of Highly Cytotoxic Natural Killer Cells for Treatment of Acute Myelogenous Leukemia Using a Feeder-Free, Particle-Based Approach (2015)

Natural killer (NK) cell immunotherapy as a cancer treatment shows promise, but expanding NK cells consistently from a small fraction (∼ 5%) of peripheral blood mononuclear cells (PBMCs) to therapeutic amounts remains challenging. Most current ex vivo expansion methods use co-culture with feeder cells (FC), but their use poses challenges for wide clinical application. We developed a particle-based NK cell expansion technology that uses plasma membrane particles (PM-particles) derived from K562-mbIL15-41BBL FCs. These PM-particles induce selective expansion of NK cells from unsorted PBMCs, with NK cells increasing 250-fold (median, 35; 10 donors; range, 94 to 1492) after 14 days of culture and up to 1265-fold (n = 14; range, 280 to 4426) typically after 17 days. The rate and efficiency of NK cell expansions with PM-particles and live FCs are comparable and far better than stimulation with soluble 41BBL, IL-15, and IL-2. Furthermore, NK cells expand selectively with PM-particles to 86% (median, 35; range, 71% to 99%) of total cells after 14 days. The extent of NK cell expansion and cell content was PM-particle concentration dependent. These NK cells were highly cytotoxic against several leukemic cell lines and also against patient acute myelogenous leukemia blasts. Phenotype analysis of these PM-particle-expanded NK cells was consistent with an activated cytotoxic phenotype. This novel NK cell expansion methodology has promising clinical therapeutic implications.
Polarization-Engineered III-Nitride Heterojunction Tunnel Field-Effect Transistors (2015)

The concept and simulated device characteristics of tunneling field-effect transistors (TFETs) based on III-nitride heterojunctions are presented for the first time. Through polarization engineering, interband tunneling can become significant in III-nitride heterojunctions, leading to the potential for a viable TFET technology. Two prototype device designs, inline and sidewall-gated TFETs, are discussed. Polarization-assisted p-type doping is used in the source region to mitigate the effect of the deep Mg acceptor level in p-type GaN. Simulations indicate that TFETs based on III-nitride heterojunctions can be expected to achieve ON/ OFF ratios of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$10^{6}$ </tex-math></inline-formula> or more, with switching slopes well below 60 mV/decade, ON-current densities approaching 100 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{A}/\mu \text{m}$ </tex-math></inline-formula> , and energy delay products as low as 67 aJ-ps/ <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> .
Palladium‐Catalyzed Construction of Quaternary Stereocenters by Enantioselective Arylation of γ‐Lactams with Aryl Chlorides and Bromides (2019)

Abstract Herein, we report the first Pd‐catalyzed enantioselective arylation of α‐substituted γ‐lactams. Two sets of conditions were developed for this transformation, allowing for the use of either aryl chlorides or bromides as electrophiles. Utilizing a highly electron‐rich dialkylphosphine ligand we have been able to construct α‐quaternary centers in good yields (up to 91 % yield) and high enantioselectivities (up to 97 % ee ).