gebhart/patrepeval huggingface dataset:
P-003 development of an endovascular magnetic filter device to enable high dose intra-arterial chemotherapy: finite element modeling (2015)

<h3>Purpose</h3> A temporary endovascular magnetic filter was developed to remove iron oxide particles conjugated to chemotherapeutics from the blood, preventing chemotherapeutics from circulating where it is not needed to reduce systemic toxicity and enable higher dose therapy. Magnetically targeted drug delivery through filtration could play an important role in expanding intra-arterial therapy to head and neck cancer. Previous proof-of-concept established rapid high-capacity binding of iron oxide particles in swine serum <i>in vitro</i>, and preliminary demonstration of qualitative efficacy <i>in vivo</i> in a porcine model. In this study, we aim to optimize the filtration efficacy of the prototype through finite element magnetic modeling. <h3>Method</h3> Magnetic modeling was performed in 2D using Finite Element Method Magnetics (FEMM) software (Brighton, MA). Prototype designs consisting of individual neodymium N52 magnets were simulated to optimize the following parameters: i) magnetization across length vs diameter, ii) magnet orientations aligned or reversed, iii) magnet spacing, and iv) magnet length. The average magnetic flux gradient (∇B<sub>y</sub>) was computed across a unit length consisting of one magnet and adjoining gap space as shown in Figure 1A. ∇B<sub>y</sub> is directly correlated to the magnetic force on an iron particle, and was plotted as against D, distance from the surface of the magnet. Designs with greater ∇B<sub>y</sub> at high D were considered more effective. <h3>Results</h3> Designs with magnetization across the length and reversed (like polarities facing and repelling each other), had slightly higher ∇B<sub>y</sub> than designs with magnetization across the diameter and aligned (opposite polarities facing and attracting each other). Magnetization across the length and aligned, and magnetization across the diameter and reversed both had low ∇B<sub>y</sub> at high D. For designs with magnetization across the length and reversed orientations as shown in Figure 1B, reduced spacing between magnets increased ∇B<sub>y</sub>. Reduced magnet length increased ∇B<sub>y</sub> at low D, at the expense of ∇B<sub>y</sub> at high D. <h3>Conclusions</h3> The current endovascular magnetic filter prototype could be improved by using longer magnets magnetized across the length in the reversed orientation with like polarities repelling each other and minimal spacing between magnets. <h3>Disclosures</h3> C. Sze: 1; C; NIH NCI. 5; C; ChemoFilter. M. Mabray: None. P. Lillaney: None. S. Kondapavulur: None. D. Liu: None. M. Wilson: 1; C; NIH NCI. 6; C; Penumbra. S. Hetts: 1; C; NIH NCI. 6; C; Penumbra.
Synthesis and Cell-Based Activity of a Potent and Selective Protein Tyrosine Phosphatase 1B Inhibitor Prodrug (2007)

Our laboratory recently reported the development of novel prodrug chemistry for the intracellular delivery of phosphotyrosine mimetics. This chemistry has now been adapted for the synthesis of a prodrug that delivers the nonhydrolyzable difluoromethylphosphonate moiety intracellularly. Activation of the prodrug generates a difluoromethylphosphonamidate anion that undergoes subsequent cyclization and hydrolysis with a t1/2 = 44 min. A highly potent and selective inhibitor of protein tyrosine phosphatase 1B (PTP1B) with a nanomolar Ki has been reported, but this bis(difluoromethylphosphonate) lacks potential utility due to its exceedingly low membrane permeability at physiological pH. A prodrug of this inhibitor has been synthesized and evaluated in a cell-based assay. The prodrug exhibits nanomolar PTP1B inhibitory activity in this assay, confirming the efficacy of intracellular phosphonate delivery using this prodrug approach.
RFIDs and secret handshakes (2008)

We tackle the problem of defending against ghost-and-leech (a.k.a. proxying, relay, or man-in-the-middle) attacks against RFID tags and other contactless cards. The approach we take -- which we dub secret handshakes -- is to incorporate gesture recognition techniques directly on the RFID tags or contactless cards. These cards will only engage in wireless communications when they internally detect these secret handshakes. We demonstrate the effectiveness of this approach by implementing our secret handshake recognition system on a passive WISP RFID tag with a built-in accelerometer. Our secret handshakes approach is backward compatible with existing deployments of RFID tag and contactless card readers.
Fast detection of a protozoan pathogen, <i>Perkinsus marinus</i>, using AlGaN/GaN high electron mobility transistors (2009)

Antibody-functionalized, Au-gated AlGaN/GaN high electron mobility transistors (HEMTs) were used to detect Perkinsus marinus. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN/GaN HEMT drain-source current showed a rapid response of less than 5 s when the infected solution was added to the antibody-immobilized surface. The sensor can be recycled with a phosphate buffered saline wash. These results clearly demonstrate the promise of field-deployable electronic biological sensors based on AlGaN/GaN HEMTs for Perkinsus marinus detection.
Anti-idiotype-induced, lipopolysaccharide-specific antibody response to <i>Pseudomonas aeruginosa</i> . (1990)

Antibody directed to the O-specific polysaccharide (Ps) side chain of Pseudomonas aeruginosa LPS provides immunotype-specific protection against infection by virtue of enhancing opsonophagocytosis. We have developed a syngeneic anti-idiotypic antibody (mAb2) directed to a functionally active monoclonal immunotype 1 Ps-antibody (mAb1). The mAb2 performed as a molecular mimic of Ps as evidenced by 1) blocking of mAb1/mAb2 interaction by Ps, 2) blocking of mAb1/Ps binding by mAb2, 3) cross-species binding of mAb2 to human Ps antibodies from individuals immunized with the same immunotype 1 Ps, and 4) induction of anti-LPS antibody by immunization with mAb2 in syngeneic mice. Our studies thus show that an anti-idiotypic antibody may functionally mimic the O-polysaccharide of P. aeruginosa LPS, and bind to cross-reactive Id present in human Ps antibodies. We have further shown that this anti-idiotypic antibody induces anti-LPS antibody when used as an Ag in syngeneic mice, suggesting that this approach may eventually be used to successfully immunize humans.
Soliton compression to ultra-short pulses using cascaded quadratic nonlinearities in silica photonic crystal fibers (2007)

We investigate the possibility of using poled silica photonic crystal fibers for self-defocusing soliton compression with cascaded quadratic nonlinearities. Such a configuration has promise due to the desirable possibility of reducing the group-velocity mismatch. However, this unfortunately leads to increased phase mismatch, and the dispersion is often anomalous. All this reduces the design parameter space where soliton compression is possible, and poses strong requirements on the poling efficiency. We propose to use quasi-phase matching in order to reach realistic requirements on the quadratic nonlinearity, and show that compression of nJ pulses to few-cycle duration is possible in such a fiber. A small amount of group-velocity mismatch optimizes the compression.
A Family of Negative Regulators Targets the Committed Step of de Novo Fatty Acid Biosynthesis (2016)

Acetyl-CoA carboxylase (ACCase) catalyzes the committed step of de novo fatty acid biosynthesis. In prokaryotes, green algae, and most plants, this enzyme is a heteromeric complex requiring four different subunits for activity. The plant complex is recalcitrant to conventional purification schemes and hence the structure and composition of the full assembly have been unclear. In vivo coimmunoprecipitation using subunit-specific antibodies identified a novel family of proteins in <i>Arabidopsis thaliana</i> annotated as biotin/lipoyl attachment domain containing (BADC) proteins. Results from yeast two-hybrid and coexpression in <i>Escherichia coli</i> confirmed that all three BADC isoforms interact with the two biotin carboxyl carrier protein (BCCP) isoforms of Arabidopsis ACCase. These proteins resemble BCCP subunits but are not biotinylated due to a mutated biotinylation motif. We demonstrate that BADC proteins significantly inhibit ACCase activity in both <i>E. coli</i> and Arabidopsis. Targeted gene silencing of BADC isoform 1 in Arabidopsis significantly increased seed oil content when normalized to either mass or individual seed. We conclude the BADC proteins are ancestral BCCPs that gained a new function as negative regulators of ACCase after initial loss of the biotinylation motif. A functional model is proposed.
A new wideband modelling technique for spiral inductors (2004)

A new wideband modelling technique is presented, to exactly model the time-domain (TD) responses of microwave spiral inductors. This new method is suitable for modelling the spiral inductors used in switching-type microwave circuits, such as LC tank voltage-controlled oscillators (VCOs), or filters. The technique was developed based on applying an ultra-short impulse signal (30 ps) to the device. Furthermore, the layer-peeling technique (LPT) and hybrid equivalent circuits were used in the modelling process. Experiments were conducted to reveal the feasibility of the technique. Results show that the generated wideband models can be used to describe the TD responses of spiral inductors with a timescale down to picosecond order.
Complete Genome Sequence of <i>Neisseria meningitidis</i> Serogroup B Strain MC58 (2000)

The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.
Real-time energy-optimal trajectory generation for a servo motor (2013)

This paper considers the fast generation of speed and acceleration constrained energy-optimal trajectories for a motor system performing a point-to-point positioning task with a fixed final time. An algorithm is proposed to obtain the energy-optimal solution by solving a series of Two-point Boundary Value Problems (TBVPs) with guaranteed convergence. The algorithm is capable of generating energy-optimal trajectories in real-time.
Siderophore Conjugates of Daptomycin are Potent Inhibitors of Carbapenem Resistant Strains of <i>Acinetobacter baumannii</i> (2018)

Development of resistance to antibiotics is a major medical problem. One approach to extending the utility of our limited antibiotic arsenal is to repurpose antibiotics by altering their bacterial selectivity. Many antibiotics that are used to treat infections caused by Gram-positive bacteria might be made effective against Gram-negative bacterial infections, if they could circumvent permeability barriers and antibiotic deactivation processes associated with Gram-negative bacteria. Herein, we report that covalent attachment of the normally Gram-positive-only antibiotic, daptomycin, with iron sequestering siderophore mimetics that are recognized by Gram-negative bacteria, provides conjugates that are active against virulent strains of Acinetobacter baumannii, including carbapenemase and cephalosporinase producers. The result is the generation of a new set of antibiotics designed to target bacterial infections that have been designated as being of dire concern.
Bacteriorhodopsin-based volumetric optical memory (2002)

We explore the use of the protein bacteriorhodopsin as the recording medium in an all-optical three-dimensional memory. Three-dimensional memory architectures offer as much as a thousand-fold improvement in memory storage over current storage technology. Although bacteriorhodopsin has been used previously as the active memory element in a number of three-dimensional architectures (e.g. holographic and two-photon), a sequential single-photon volumetric architecture employing a photochemical branching reaction characteristic of the protein is currently showing the most promise. This unique branching reaction allows for long-term storage by the protein. During the past two years, a prototype has been constructed by using a number of commercially available components, including spatial light modulators and microdiode lasers. Chemical, genetic, and optical technologies optimize the writing and reading efficiencies of the protein based memory. For example, gray-scale and polarization multiplexing are capable of increasing the storage capacity ten-fold. Although a number of issues still must be resolved with respect to commercialization, cost, and performance, the promise of both increased speed (via parallel reading and writing operations) and storage density, make volumetric memories a potentially viable alternative to conventional technologies.
Dapagliflozin and diuretic utilization in heart failure with mildly reduced or preserved ejection fraction: the DELIVER trial (2023)

In patients with heart failure with mildly reduced or preserved ejection fraction, the clinical benefits of dapagliflozin relative to placebo were consistent across a wide range of diuretic categories and doses with a similar safety profile. Treatment with dapagliflozin significantly reduced new loop diuretic requirement over time.
Inertio-elastic focusing of bioparticles in microchannels at high throughput (2014)

Abstract Controlled manipulation of particles from very large volumes of fluid at high throughput is critical for many biomedical, environmental and industrial applications. One promising approach is to use microfluidic technologies that rely on fluid inertia or elasticity to drive lateral migration of particles to stable equilibrium positions in a microchannel. Here, we report on a hydrodynamic approach that enables deterministic focusing of beads, mammalian cells and anisotropic hydrogel particles in a microchannel at extremely high flow rates. We show that on addition of micromolar concentrations of hyaluronic acid, the resulting fluid viscoelasticity can be used to control the focal position of particles at Reynolds numbers up to Re≈10, 000 with corresponding flow rates and particle velocities up to 50 ml min−1 and 130 m s−1. This study explores a previously unattained regime of inertio-elastic fluid flow and demonstrates bioparticle focusing at flow rates that are the highest yet achieved.
Gravity-Balanced Test Stand for Testing Micro Air Vehicles (2009)

For the purpose of safety, test stands are usually used for testing small or micro unmanned aerial vehicles (UAVs), especially in the early test stage. Although a test stand can prevent the tested vehicle from flying out of control or crashing, it adds extra burden to the vehicle due to the weight of the stand’s moving mechanism. This is a major problem for micro air vehicles (MAVs) because of their very limited lifting or payload capability. This paper presents an innovative solution to this problem by using a passive gravity-balanced test stand. Designed based on the static gravity balancing technique, the test stand is capable of completely compensating its own weight, so that the test vehicle, while flying with the stand, will not have the extra burden from the weight of the test stand. A hardware prototype of the test stand has been designed and built, which demonstrated the effectiveness of the new technology. Nomenclature A = distance from the pivot point to the cable connection point d1 = vertical distance from pivot to pulley 1 d2 = vertical distance from pivot to pulley 2 g = gravitational acceleration h1 = height from the X-Y plane or the ground to the lower bar of the arm h2 = distance from the lower bar to the upper bar of the arm k1 = stiffness of spring 1 k2 = stiffness of spring 2 l1 = length of the inner section l2 = length of the outer section m1 = mass of each upper and lower part of the inner section m2 = mass of each upper and lower part of the outer section m12 = mass of connecting link with pulley m3 = mass of landing mechanism θ1 = angle between inner section and vertical θ2 = angle between outer section and vertical
Postirradiation polymerization of e-beam negative resists: Theoretical analysis and method of inhibition (1981)

Many e-beam negative resists show postirradiation polymerization, i.e., even after e-beam irradiation termination, crosslinking reaction continues. This phenomenon shows an unfavorable effect in precise pattern fabrication; the first delineated portion of the resist undergoes a dimensional change with respect to the last-delineated portion. A method to inhibit postirradiation polymerization is presented based on a theoretical analysis of the postpolymerization mechanism. In the model used for analysis, active radicals are not extinguished in the vacuum and polymerization proceeds at a rate proportional to the radical concentration (first order reaction). A radical loses its activity due to collision with another radical (second-order reaction ). This model successfully explained experimental results. Postirradiation polymerization inhibition is achieved by adding a radical scavenger to resists. Active radical collision with a scavenger also extinguishes radical activity. Thus resist pattern width and thickness are freed from time dependence after irradiation. Resolution is also improved by postpolymerization inhibition as chain reactions in resists are suppressed. Although sensitivity is decreased, a highly sensitive negative resist can meet today’s requirement (around 1 μC/cm2), even after the addition of a scavenger. To demonstrate the benefit of postirradiation polymerization inhibition, a Cr mask was made with submicron features. It has 7-μm period Y-Y propagation patterns for a bubble memory, in which all gaps are designed as 0.5 μm. Adding a radical scavenger, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and SEL-N resist, precise pattern fabrication was achieved, irrespective of the time after exposure.
Photoacoustic monitoring of circulating tumor cells released during medical procedures (2013)

Many cancer deaths are related to metastasis to distant organs due to dissemination of circulating tumor cells (CTCs) shed from the primary tumor. For many years, oncologists believed some medical procedures may provoke metastasis; however, no direct evidence has been reported. We have developed a new, noninvasive technology called in vivo photoacoustic (PA) flow cytometry (PAFC), which provides ultrasensitive detection of CTCs. When CTCs with strongly light-absorbing intrinsic melanin pass through a laser beam aimed at a peripheral blood vessel, laser-induced acoustic waves from CTCs were detected using an ultrasound transducer. We focused on melanoma as it is one of the most metastatically aggressive malignancies. The goal of this research was to determine whether melanoma manipulation, like compression, incisional biopsy, or tumor excision, could enhance penetration of cancer cells from the primary tumor into the circulatory system. The ears of nude mice were inoculated with melanoma cells. Blood vessels were monitored for the presence of CTCs using in vivo PAFC. We discovered some medical procedures, like compression of the tumor, biopsy, and surgery may either initiate CTC release in the blood which previously contained no CTCs, or dramatically increased (10-30–fold) CTC counts above the initial level. Our results warn oncologists to use caution during physical examination, and surgery. A preventive anti-CTC therapy during or immediately after surgery, by intravenous drug administration could serve as an option to treat the resulting release of CTCs.
An Efficient Synthesis of Novel Estrieno[2.3‐b] and [3.4‐c]Pyrroles. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Advantages of fluorescence-mediated tomography: a prelude to molecular interrogations in deep tissues (2002)

We present certain experimental advantages of fluorescence measurements versus intrinsic contrast measurements pertaining to imaging the distribution of fluorochromes in tissue by means of a normalized Born expansion. Based on these observations we derive an appropriate reconstruction algorithm that concurrently uses intrinsic and fluorescence contrast that facilitates fluorescence-mediated molecular tomography in tissues in-vivo. In contrast to the standard Born approximation, the proposed algorithm does not require instrument calibration or absolute photon fluence measurements. Therefore it is ideally suited for experimental tomographic investigations of tissue in the near-infrared region. We have used this algorithm to image and quantify cancer associated cathepsin B expression in cancer animal models.
Photonic crystal spectrometer (2010)

We demonstrate a new kind of optical spectrometer employing photonic crystal patterns to outcouple waveguided light from a transparent substrate. This spectrometer consists of an array of photonic crystal patterns, nanofabricated in a polymer on a glass substrate, combined with a camera. The camera captures an image of the light outcoupled from the patterned substrate; the array of patterns produces a spatially resolved map of intensities for different wavelength bands. The intensity map of the image is converted into a spectrum using the photonic crystal pattern response functions. We present a proof of concept by characterizing a white LED with our photonic crystal spectrometer.
The rational design of potential chemotherapeutic agents: Synthesis of bryostatin analogues (1999)

The bryostatins are a unique family of cancer chemotherapeutic candidates isolated from marine bryozoa. While their molecular mode of action is not known, these macrolactones exhibit high affinities for protein kinase C (PKC) isozymes, compete for the phorbol ester binding site on PKC, and stimulate kinase activity in vitro and in vivo. Unlike the phorbol esters, they do not act as tumor promoters. Despite promising biological properties, the supply of these compounds is limited by the difficulty of their isolation from natural sources and their synthetic complexity. A new class of bryostatin analogues which retain the putative recognition domain of the bryostatins but are simplified through deletions and modifications in the C1-C14 spacer domain have been designed using computer models. A convergent synthesis has been realized for the production, in gram quantities, of these recognition and spacer domains whose coupling allows for the generation of a range of analogues. The final closure process involves a novel macrotransacetalization reaction which proceeds with complete stereoselectivity. The solution structures of two synthetic analogues were determined by NMR spectroscopy and found to be very similar to the previously reported structures of bryostatins 1 and 10. In addition, these structures appear to indicate that the stereochemistry of the C3 hydroxyl group plays a significant role in the conformation of the macrolactone. All analogues bound strongly to a mixture of PKC isozymes, and several exhibited significant levels of in vitro growth inhibitory activity against human cancer cell lines. Taken together, this work provides important steps toward the development and understanding of simplified, synthetically accessible analogues of the bryostatins as potential chemotherapeutic agents.