gebhart/patrepeval huggingface dataset:
Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis (2019)

Distinguishing malignant cells from non-neoplastic ones is a major challenge in triple-negative breast cancer (TNBC) treatment. Here, we developed a complementary targeting strategy that uses precisely matched, multivalent ligand-receptor interactions to recognize and target TNBC tumors at the primary site and metastatic lesions. We screened a panel of cancer cell surface markers and identified intercellular adhesion molecule-1 (ICAM1) and epithelial growth factor receptor (EGFR) as optimal candidates for TNBC complementary targeting. We engineered a dual complementary liposome (DCL) that precisely complements the molecular ratio and organization of ICAM1 and EGFR specific to TNBC cell surfaces. Our in vitro mechanistic studies demonstrated that DCLs, compared to single-targeting liposomes, exhibited increased binding, enhanced internalization, and decreased receptor signaling. DCLs consistently exhibited substantially increased tumor targeting activity and antitumor efficacy in orthotopic and lung metastasis models, indicating that DCLs are a platform technology for the design of personalized nanomedicines for TNBC.
Triazole antifungals. II. Synthesis and antifungal activities of 3-acyl-4-methyloxazolidine derivatives. (1990)

Triazole compounds with an oxazolidine ring were designed and synthesized as a potential inhibitor of the fungal cytochrome P450 14 alpha-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (4R,5R)-3-acyl-4-methyloxazolidine derivatives 4 exhibited remarkably high efficacy after oral or parenteral dosing. The potent activity of 4 is hypothesized to be a consequence of a structural similarity between 4 and lanosterol, a target molecule of the cytochrome P450 14 alpha-demethylase. Highly stereoselective synthesis of these oxazolidines is also described.
Controlling gas-phase reactions for efficient charge reduction electrospray mass spectrometry of intact proteins (2005)

Charge reduction electrospray mass spectrometry (CREMS) reduces the charge states of electrospray-generated ions, which concentrates the ions from a protein into fewer peaks spread over a larger m/z range, thereby increasing peak separation and decreasing spectral congestion. An optimized design for a CREMS source is described that provides an order-of-magnitude increase in sensitivity compared to previous designs and provides control over the extent of charge reduction. Either a corona discharge or an alpha-particle source was employed to generate anions that abstract protons from electrosprayed protein cations. These desired ion/ion proton transfer reactions predominated, but some oxidation and ion-attachment reactions also occurred, leading to new peaks or mass-shifted broader peaks while decreasing signal intensity. The species producing these deleterious side-reactions were identified, and conditions were found that prevented their formation. Spectrometer m/z biases were examined because of their effect upon the signal intensity of higher m/z charge-reduced protein ions. The utility of this atmospheric pressure CREMS was demonstrated using a cell lysate fraction from E. coli. The spectral simplification afforded by CREMS reveals more proteins than are observed without charge reduction.
Effect of Sub-Loop Tube on Energy Conversion Efficiency of Loop-Tube-Type Thermoacoustic System (2010)

For the practical application of a loop-tube-type thermoacoustic system, it is important to improve its energy conversion efficiency. We propose a loop-tube-type thermoacoustic system with a diverging sub-loop tube. The sub-loop tube diverges from the main loop tube and rejoins it so that the sub-loop tube forms a loop. The main loop tube is 0.85 m high and 0.5 m wide, with 3.3 m total length. The sub-loop tube’s length from the upper side to the lower side is 0.45 m. The sub tube position is changed so that the distance from the heater to the upper part of the sub tube is 1.73, 1.83, or 1.93 m. The pressure, the phase difference between the pressure and particle velocity, and the sound intensity were calculated using a two-sensor power method with pressure measurement results. The smallest phase difference distribution was observed when the sub-loop tube is connected at 1.93 m. The highest sound intensity of 13 kW/m 2 was obtained at the prime mover top end, when a sub-loop tube was connected at 1.93 m. Because the sound intensity was 0.65 kW/m2 when a sub-loop tube was not connected, it was increased about 20-fold by connecting a sub-loop tube. The decrease in the phase difference indicates that the phase difference in the prime mover became a traveling wave phase, and this raises the energy conversion efficiency from heat to sound.
Determinants of Endometrial Receptivity (2004)

Understanding the molecular changes that occur during the window of implantation is fundamental to our knowledge of human reproduction. Lately, the development of microarray technology has allowed this process to be studied from a global molecular perspective. In the last 2 years, researchers have focused their efforts on throwing light on the gene expression profile of the receptive endometrium. The genes hold the key to the development of the endometrium at any stage, and we have focused our work on the window of implantation. The four most recently published works in this field have revealed a long list of genes that are up- or downregulated at the time of implantation. Although these studies have been conducted using varying approaches, collectively these studies identify new candidate markers that can be used to accurately diagnose the receptive state of the endometrium. The next step is to perform functional analysis for confirming the importance of these genes. In this article, we gather together these recent findings to provide an overview of the current knowledge regarding the genetic functioning of human endometrial receptivity and related processes.
<i>In vitro</i>neutralization of prions with PrP<sup>Sc</sup>-specific antibodies (2015)

Prion diseases reflect the misfolding of a self-protein (PrP(C)) into an infectious, pathological isomer (PrP(Sc)). By targeting epitopes uniquely exposed by misfolding, our group developed PrP(Sc)-specific vaccines to 3 disease specific epitopes (DSEs). Here, antibodies induced by individual DSE vaccines are evaluated for their capacity to neutralize prions in vitro. For both purified antibodies and immunoreactive sera, the PrP(Sc)-specific antibodies were equally effective in neutralizing prions. Further, there was no significant increase in neutralizing activity when multiple DSEs were targeted within an assay. At a low antibody concentration, the PrP(Sc)-specific antibodies matched the neutralization achieved by an antibody that may act via both PrP(C) and PrP(Sc). At higher doses, however, this pan-specific antibody was more effective, potentially due to a combined deactivation of PrP(Sc) and depletion of PrP(C).
Inhibition of the lncRNA SAF drives activation of apoptotic effector caspases in HIV-1–infected human macrophages (2019)

Long noncoding RNAs (lncRNAs) impart significant regulatory functions in a diverse array of biological pathways and manipulation of these RNAs provides an important avenue to modulate such pathways, particularly in disease. Our knowledge about lncRNAs' role in determination of cellular fate during HIV-1 infection remains sparse. Here, we have identified the impact of the lncRNA SAF in regulating apoptotic effector caspases in macrophages, a long-lived cellular reservoir of HIV-1, that are largely immune to virus-induced cell death. Expression of SAF is significantly up-regulated in HIV-1-infected human monocyte-derived macrophages (MDM) compared with bystander and virus-nonexposed cells. A similar enhancement in SAF RNA expression is also detected in the HIV-1-infected airway macrophages obtained by bronchoalveolar lavage of HIV-1-infected individuals. Down-regulation of SAF with siRNA treatment increases caspase-3/7 activity levels in virus-infected MDMs. This induction of apoptotic caspases occurs exclusively in HIV-1-infected macrophages and not in bystander cells, leading to a significant reduction in HIV-1 replication and overall viral burden in the macrophage culture. This study identifies targeting of the lncRNA SAF as a potential means to specifically induce cell death in HIV-1-infected macrophages.
Incremental Entity Resolution from Linked Documents (2014)

In many government applications we often find that information about entities, such as persons, are available in disparate data sources such as passports, driving licences, bank accounts, and income tax records. Similar scenarios are commonplace in large enterprises having multiple customer, supplier, or partner databases. Each data source maintains different aspects of an entity, and resolving entities based on these attributes is a well-studied problem. However, in many cases documents in one source reference those in others; e.g., a person may provide his driving-licence number while applying for a passport, or vice-versa. These links define relationships between documents of the same entity (as opposed to inter-entity relationships, which are also often used for resolution). In this paper we describe an algorithm to cluster documents that are highly likely to belong to the same entity by exploiting inter-document references in addition to attribute similarity. Our technique uses a combination of iterative graph-traversal, locality-sensitive hashing, iterative match-merge, and graph-clustering to discover unique entities based on a document corpus. A unique feature of our technique is that new sets of documents can be added incrementally while having to re-resolve only a small subset of a previously resolved entity-document collection. We present performance and quality results on two data-sets: a real-world database of companies and a large synthetically generated `population' database. We also demonstrate benefit of using inter-document references for clustering in the form of enhanced recall of documents for resolution.
High-Performance Chemical Sensing Using Schottky-Contacted Chemical Vapor Deposition Grown Monolayer MoS<sub>2</sub> Transistors (2014)

Trace chemical detection is important for a wide range of practical applications. Recently emerged two-dimensional (2D) crystals offer unique advantages as potential sensing materials with high sensitivity, owing to their very high surface-to-bulk atom ratios and semiconducting properties. Here, we report the first use of Schottky-contacted chemical vapor deposition grown monolayer MoS2 as high-performance room temperature chemical sensors. The Schottky-contacted MoS2 transistors show current changes by 2-3 orders of magnitude upon exposure to very low concentrations of NO2 and NH3. Specifically, the MoS2 sensors show clear detection of NO2 and NH3 down to 20 ppb and 1 ppm, respectively. We attribute the observed high sensitivity to both well-known charger transfer mechanism and, more importantly, the Schottky barrier modulation upon analyte molecule adsorption, the latter of which is made possible by the Schottky contacts in the transistors and is not reported previously for MoS2 sensors. This study shows the potential of 2D semiconductors as high-performance sensors and also benefits the fundamental studies of interfacial phenomena and interactions between chemical species and monolayer 2D semiconductors.
A Combustion Control and Diagnostics Sensor for Gas Turbines (2004)

The implementation of sophisticated combustion control schemes in modern gas turbines is motivated by the desire to maximize thermodynamic efficiency while meeting NOx emission restrictions. To achieve target NOx levels, modern turbine combustors must operate with a finely controlled fuel-air ratio near the fuel-lean flame extinction limit, where the combustor is most susceptible to instabilities. In turbine configurations with multiple combustors arranged around the annulus, differences in flow splits caused by manufacturing variations or engine wear can compromise engine performance. Optimal combustion control is also complicated by changes in environmental conditions, fuel-quality, or fuel-type. As a consequence, engines must be commissioned in the field with adequate stability margin such that manufacturing tolerances, normally expected component wear, fuel-quality, and environmental conditions will not cause unstable combustion. A lack of robust combustion in-situ monitoring has limited the ability of modern turbines to achieve stable ultra-low emission performance over the entire load range. This paper describes a combustion control and diagnostics sensor (CCADS) that can potentially revolutionize the manner in which modern gas turbines are controlled. This robust sensor uses the electrical properties of the flame to detect key events and monitor critical operating parameters within the combustor. The CCADS is integrated into the fuel nozzle such that low cost and long life are achieved. Tests conducted at turbine conditions in laboratory combustors instrumented with CCADS have demonstrated the following potential capabilities: 1) detection of incipient flashback and autoignition 2) detection of incipient lean blowout 3) detection of dynamic pressure oscillations 4) and a qualitative measure of equivalence ratio within the combustor. Many of these capabilities have been reported in other publications with data from an atmospheric combustion rig. This paper will summarize each of the capabilities with recent data at turbine conditions. The expectation is that CCADS will provide the key in-situ monitoring for diagnostics and control of modern gas turbines, allowing them to achieve stable ultra-low emissions performance.
Design and synthesis of cobalt(<scp>III</scp>) nitrogen mustard complexes as hypoxia selective cytotoxins. The X-ray crystal structure of bis(3-chloropentane-2,4-dionato)(RS-N,N′-bis(2-chloroethyl)ethylenediamine)cobalt(<scp>III</scp>) perchlorate, [Co(Clacac)<sub>2</sub>(bce)]ClO<sub>4</sub> (1991)

The design, synthesis and biological evaluation of [Co(Meacac)2(dce)]+, a cobalt(III) nitrogen mustard complex that is effective as a hypoxia selective cytotoxin for potential anti-cancer use, is reported.
Reductions with Lithium in Low Molecular Weight Amines and Ethylenediamine (2000)

Reductions of several types of compounds with lithium and ethylenediamine using low molecular weight amines as solvent are described. In all cases 1 mol of ethylenediamine or N, N'-dimethylethylenediamine per gram-atom of lithium was used. In some cases it was beneficial to add an alcohol as a proton donor. These reaction conditions were applied to the debenzylation of N-benzylamide and lactams which are refractory to hydrogenolysis with hydrogen and a catalyst. N-Benzylpilolactam 2, synthesized from pilocarpine hydrochloride in refluxing benzylamine, was debenzylated in good yield using 10 gram-atoms of lithium per mole (10 Li/mol) of 2 in n-propylamine. The debenzylation of N-benzyl-N-methyldecanoic acid amide, 4 (6 Li/mol), in t-butylamine/N, N'-dimethylethylenediamine gave N-methyldecanoic acid amide 6 in 70% yield. Alternatively, reduction of 4 (7 Li/mol) in t-butanol/n-propylamine/ethylenediamine gave n-decanal 12 in 36% yield. Using the same conditions, thioanisole, 1-adamantane-p-toluenesulfonamide, and 1-adamantane methyl p-toluenesulfonate were reduced with 3, 7, and 7.2 Li/mol of compound to give thiophenol (74%), adamantamine (91%), and 1-adamantane methanol (75%), respectively. In this solvent system naphthalene and 3-methyl-2-cyclohexene-1-one were reduced to isotetralin (74%) and 3-methyl cyclohexanone (quantitative) with 5 and 2.2 Li/mol of starting compound, respectively. Oximes and O-methyloximes were reduced to their corresponding amines using 5 and 8 Li/mol of compound, respectively. Anisole was also reduced to 1-methoxy-1,4-cyclohexadiene with 2.5 Li/mol of anisole. Undecanenitrile was reduced to undecylamine with 8.6 Li/mol. Additionally, a base-catalyzed formation of imidazolines from a nitrile and ethylenediamine was also explored.
Distributed feedback buried heterostructure diode laser (1976)

We report room-temperature operation of a buried heterostructure distributed feedback diode laser. The device operates in a single TE polarized longitudinal mode over a temperature range from 232 to 324 K and exhibits a temperature sensitivity of 0.72 Å/K. In comparison, the variation for a similar Fabry-Perot diode is 3.4 Å/K.
Determination of Sheep Prion Gene Polymorphisms from Paraffin-Embedded Tissue (2006)

Amino acid polymorphisms of the prion protein (PrP) greatly influence the susceptibility of sheep to scrapie. Selective breeding to increase the prevalence of PrP gene alleles associated with scrapie resistance is a flock management practice that is important for scrapie control programs. Determination of sheep PrP alleles typically has required extraction of DNA from host tissues that are freshly derived or stored frozen. We describe application of a DNA extraction procedure for formalin-fixed, paraffin-embedded tissues (PET) for the purpose of PCR amplification and nucleotide sequencing of relevant codons (136-171) of the sheep PrP gene. Tissues derived from 96 sheep were studied. The DNA sequence identity was confirmed in 87 of 94 matched samples of PET and frozen tissue specimens. DNA from brainstem PET of 2 sheep, from which fresh tissue was not available, was amplified and sequenced after formalin fixation for 7-70 days. This method will allow retrospective analysis of PrP genetics of sheep subsequent to postmortem diagnosis of scrapie when nonfixed tissue is unavailable for DNA extraction; however, it is not recommended that submission of fixed tissue supplant collection of fresh tissues for the purpose of determining PrP gene polymorphisms.
Calibration-Free Second Harmonic Generation (SHG) Image Analysis for Quantification of Trace Crystallinity Within Final Dosage Forms of Amorphous Solid Dispersions (2018)

A statistical model enables auto-calibration of second harmonic generation (SHG) images for quantifying trace crystallinity within amorphous solid dispersions (ASDs) over a wide dynamic range of crystallinity. In this paper, we demonstrate particle-counting approaches for quantifying trace crystallinity, combined with analytical expressions correcting for particle overlap bias in higher crystallinity regimes to extend the continuous dynamic range of standard particle-counting algorithms through to the signal averaging regime. The reliability of the values recovered by these expressions was demonstrated with simulated data as well as experimental data obtained for an amorphous solid dispersion formulation containing evacetrapib, an Eli Lilly and Company compound. Since particle counting independently recovers the crystalline volume and the SHG intensity, the average SHG intensity per unit volume can be used as an internal calibrant for quantifying crystallinity at higher volume fractions, for which particle counting is no longer applicable.
Neuropeptide mimetics for pain management (2004)

Abstract The discovery of numerous endogenous neuropeptides that participate in the formation, transmission, modulation, and perception of pain signals offers numerous strategies for the development of new analgesics. Nevertheless, the same research has not yet replaced opioids as the gold standard of pain treatment. Therefore, one possible avenue of drug development may shift interest from searching for receptor-selective opioids to creating an arsenal of drugs that target multiple opioid and non-opioid sites simultaneously. The presented short review focuses on the development of potential analgesic peptidomimetic compounds based upon opioid neuropeptides and substance P.
176-69: Feasibility of Device-based Electrical Optimization via Application of the Negative AV Hysteresis Algorithm during Cardiac Resynchronization Therapy (CRT) (2016)

Introduction: Cardiac resynchronization therapy (CRT) with MultiPoint TM Pacing (MPP) improves long-term reverse remodeling compared to conventional biventricular pacing. In this multi-center study, the reverse remodeling benefit of MPP was evaluated with respect to LV scar presence and distribution in patients who underwent scar assessment by delayed enhancement MRI (DE-MRI) prior to device implant. Methods: The transmural extent of scars was quantified for each segment in a 17-segment LV model, with scars 25% transmural excluded. CRT-D devices (Quadra Assura MP TM and Quartet TM LV lead, St Jude Medical) were programmed to maximize arterial systolic pressure assessed by a noninvasive hemodynamic system (Finometer MIDI, Finapres Medical Systems). CRT response was defined by echocardiography as .15% reduction in LV end-systolic volume at 6 mo post-implant relative to baseline (DESV). Echocardiogram and DE-MRI analyses were performed by blinded core labs. Overall scar distribution throughout the LV was classified as nonexistent (0 scar segments), remote from LV pacing electrodes (nearest scar .3 segments away), and near LV pacing electrodes (nearest scar 3 segments away), as registered to DE-MRI by fluoroscopy. Results: Twenty-two pts (68% male, EF 30 + 7%, QRS 161 + 21 ms) were enrolled in 4 EU centers and completed DE MRI and 0-6 mo echo evaluations. MPP was programmed in 19/22 pts. Of MPP pts, absolute DEF magnitudes, relative DESV magnitudes, and relative DESV response rates were positive overall, but trended higher for pts with scars (DEF 11.9 + 5.0%, DESV 33.8 + 14.0%, N 12/12 responders) vs. pts with no scars (8.0 + 6.0%, 22.6 + 23.0%, N 4/7 responders). Furthermore, the same values trended higher for pts with one or more scars near LV pacing sites (11.8 + 5.1%, 35.8 + 13.2%, N 9/9 responders) vs. without scars near the pacing sites (9.3 + 5.9%, 24.1 + 20.7%, N 7/10 responders). Conclusions: These results suggest that MPP-enabled CRT with acute hemodynamic optimization improves LV reverse remodeling regardless of scar presence or distribution, but particularly with scar tissue present and with scar tissue proximal to LV pacing sites. These observations highlight the potential of further studies relating the impact of MPP to the underlying scars in BiV non-responders.
Onion postharvest quality assessment with x-ray computed tomography – A pilot study (2017)

Onions are of major importance to the agriculture sector with an estimated world-wide production of 78.5 million metric tons. Out of these, approximately 3.7 million tons are ascribed to the United States with an aggregated farm gate value of USD 1.15 billion [1]. Onions are susceptible to bacterial and fungal infections, most critically during the short harvest period from April to May. To allow for a year-round supply, onions are stored in controlled atmosphere facilities. Infected onions, even if no decay or damage is visible, put the entire harvest in the storage facility at risk. Early detection of bacterial and fungal infections is therefore highly desirable. In this pilot study, we used a low-cost, custom-built x-ray computed tomography (CT) scanner to obtain cross-sectional images of yellow sweet Granex onions (Allium cepa) that were inoculated with pathogens. CT images were analyzed for features that could potentially be used to detect signs of pathogen-related decay in the early stages of infection. The long-term vision is to use CT scanners in an onion packinghouse to perform automated postharvest quality assessment.