gebhart/patrepeval huggingface dataset:
Benzoxazepine-Derived Selective, Orally Bioavailable Inhibitor of Human Acidic Mammalian Chitinase (2020)

Human acidic mammalian chitinase (hAMCase) is one of two true chitinases in humans, the function of which remains elusive. In addition to the defense against highly antigenic chitin and chitin-containing pathogens in the gastric and intestinal contents, AMCase has been implicated in asthma, allergic inflammation, and ocular pathologies. Potent and selective small-molecule inhibitors of this enzyme have not been identified to date. Here we describe structural modifications of compound <b>OAT-177</b>, a previously developed inhibitor of mouse AMCase, leading to <b>OAT-1441</b>, which displays high activity and selectivity toward hAMCase. Significantly reduced off-target activity toward the human ether-à-go-go-related gene (hERG) and a good pharmacokinetic profile make <b>OAT-1441</b> a potential candidate for further preclinical development as well as a useful tool compound to study the physiological role of hAMCase.
Free-space optical communications using orbital-angular-momentum multiplexing combined with MIMO-based spatial multiplexing (2015)

We explore the potential of combining the advantages of multiple-input multiple-output (MIMO)-based spatial multiplexing with those of orbital angular momentum (OAM) multiplexing to increase the capacity of free-space optical (FSO) communications. We experimentally demonstrate an 80 Gbit/s FSO system with a 2×2 aperture architecture, in which each transmitter aperture contains two multiplexed data-carrying OAM modes. Inter-channel crosstalk effects are minimized by the OAM beams' inherent orthogonality and by the use of 4×4 MIMO signal processing. Our experimental results show that the bit-error rates can reach below the forward error correction limit of 3.8×10(-3) and the power penalties are less than 3.6 dB for all channels after MIMO processing. This indicates that OAM and MIMO-based spatial multiplexing could be simultaneously utilized, thereby providing the potential to enhance system performance.
ChemInform Abstract: NOVEL SYNTHESES OF 5‐AROYL‐1,2‐DIHYDRO‐3H‐PYRROLO(1,2‐A)PYRROLE‐1‐CARBOXYLIC ACIDS (1982)

Abstract Aus Pyrrol (I) erhält man mit dem Salz (II) das Substitutionsprodukt (IIIa).
Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau (2015)

Tau is a highly abundant and multifunctional brain protein that accumulates in neurofibrillary tangles (NFTs), most commonly in Alzheimer's disease (AD) and primary age-related tauopathy. Recently, microRNAs (miRNAs) have been linked to neurodegeneration; however, it is not clear whether miRNA dysregulation contributes to tau neurotoxicity. Here, we determined that the highly conserved brain miRNA miR-219 is downregulated in brain tissue taken at autopsy from patients with AD and from those with severe primary age-related tauopathy. In a Drosophila model that produces human tau, reduction of miR-219 exacerbated tau toxicity, while overexpression of miR-219 partially abrogated toxic effects. Moreover, we observed a bidirectional modulation of tau levels in the Drosophila model that was dependent on miR-219 expression or neutralization, demonstrating that miR-219 regulates tau in vivo. In mammalian cellular models, we found that miR-219 binds directly to the 3'-UTR of the tau mRNA and represses tau synthesis at the post-transcriptional level. Together, our data indicate that silencing of tau by miR-219 is an ancient regulatory mechanism that may become perturbed during neurofibrillary degeneration and suggest that this regulatory pathway may be useful for developing therapeutics for tauopathies.
Abstract 176: Early development of GMC1, a novel molecule targeting FKBP52 for the treatment of hormone-refractory prostate cancer (2017)

Abstract Purpose: GMC1 directly inhibits FKBP52, effectively blocking androgen receptor dependent gene expression and androgen-stimulated proliferation. This make it an attractive option for the treatment of hormone-dependent and hormone-independent prostate cancer. This study investigated an analytical method for GMC1 quantification, pre-formulation characteristics of GMC1, and developed intravenous formulations for the evaluation of GMC1 in animal models. Method: An LC/MS/MS method for the quantification of GMC1 in solution, plasma and urine was developed, validated and applied to the determination of the stability, log P, plasma protein binding and solubility of GMC1 in various solvents. Liposomal formulations and co-solvent systems with various ratios of high capacity vehicles were formulated and the optimal formulation applied, at 2 mg/kg single IV bolus dose, to the pharmacokinetic study of GMC1 in a rat model. Result: The intra- and inter-day accuracy (%RE) and precision (%CV) of the LC/MS/MS method ranged from 1.6 – 11.7 % and 1.4 – 8.8 %, respectively. GMC1 is stable in solid and solution state, moderately lipophilic (log P = 1.38 ± 0.05), poorly water soluble (0.4 ± 0.01 mg/mL), and highly plasma protein bound (&gt;71%). The optimal formulation consisting of PEG 300 and Labrasol ® (1:1, v/v) allowed us to achieve a GMC1 concentration of 10 mg/mL, and tolerated an aqueous environment. GMC1 has a tri-exponential disposition with a Cmax of 7.6 ± 1.97 mg/L, clearance of 0.53 L/kg/hr, α-distribution, β-phase and terminal elimination half-lives of 0.1 ± 0.04 hr, 1.2 ± 0.34 hr, and 19.7 ± 5.09 hr respectively. Conclusion: The LC/MS/MS method, formulations and pharmacokinetic study can be applied to the pre-clinical and clinical development of GMC1. Grant Support: This work was performed under funding from NIH/NIGMS grant (5SC3GM102018) and NIH/NIMHD/RCMI grant (5G12MD007605). Citation Format: Huan Xie, Oscar Ekpenyong. Early development of GMC1, a novel molecule targeting FKBP52 for the treatment of hormone-refractory prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 176. doi:10.1158/1538-7445.AM2017-176
A measurement model for tracking hand-object state during dexterous manipulation (2010)

It is frequently accepted in the manipulation literature that tactile sensing is needed to improve the precision of robot manipulation. However, there is no consensus on how this may be achieved. This paper applies particle filtering to the problem of localizing the pose and shape of an object that the robot touches. We are motivated by the situation where the robot has enclosed its fingers around an object but has not yet grasped it. This might be the case just prior to grasping or when the robot is holding on to something fixtured elsewhere in the environment. In order to solve this problem, we propose a new model for position measurements of points on the robot manipulator that tactile sensing indicates are touching the object. We also propose a model for points on the manipulator that tactile measurements indicate are not touching the object. Finally, we characterize the approach in simulation and use it to localize an object that Robonaut 2 holds in its hand.
Robust Matrix Converter Commutation without explicit Sign Measurement (2001)

A new operation method for matrix converters is presented which eliminates the extra measuring circuits of voltage or current signs that were necessary for the commutation in the past. The paper explains the new robust method that minimises switching losses. Advantages and disadvantages of different approaches are discussed and measurements on a 5.5 kW matrix converter system are shown.
Real-time dual-microphone noise classification for environment-adaptive pipelines of cochlear implants (2013)

This paper presents an improved noise classification in environment-adaptive speech processing pipelines of cochlear implants. This improvement is achieved by using a dual-microphone and by using a computationally efficient feature-level combination approach to achieve real-time operation. A new measure named Suppression Advantage is also defined in order to quantify the noise suppression improvement of an entire pipeline due to noise classification. The noise classification and suppression improvement results are presented for four commonly encountered noise environments.
Structure-function relationships of alkaline peroxide-treated lignocellulose from wheat straw (1989)

Compared with wood pulp cellulose, alkaline H2O2-treated wheat straw [suitable for incorporation into baked foods, to reduce caloric density and increase dietary fibre levels] becomes more extensively hydrated, increases more in size when hydrated, and contains a larger glucose accessible internal vol. These and other data are interpreted, in terms of a model for alkaline H2O2-treated lignocellulose in which the residual, peroxide-resistant lignin which remains after treatment functions as a skeletal framework, preserving an open internal structure within the lignocellulosic matrix, allowing greater water penetration and more thorough hydration of cell wall polysaccharides.
Evaluation of Defects in a SiC Substrate Using the Photoluminescence Measurement Method (2022)

Photoluminescence (PL) imaging provide defect and dislocation characteristics not only in a 4H silicon carbide (SiC) epilayer but also in a substrate. In this work, to detect a large-pit or a bar-shaped stacking fault (BSF) before epilayer growth, we employed PL under various detection conditions. A large-pit was detected as a dark spot on a 4H-SiC substrate due to dislocations orthogonal to a micropipe. The BSF was clearly observed as a bright rectangle by tuning the observation conditions. The finding indicates that device killing defects or dislocations should be detected as soon as possible and thus improve the yield.
Corrosion prevention capability of polyaniline (emeraldine base and salt): An XPS study (1995)

There has been a keen interest in the use of polyaniline coatings for the corrosion protection of Fe and its alloys. To date, the primary focus has been on the doped form of the emeraldine oxidation state; also, the polyaniline has been applied, electrochemically or chemically, as an overcoat on the metal. In the present study, the surface sensitive XPS technique has been applied to investigate (1) the effectiveness of the neutral emeraldine base as well as the doped emeraldine hydrochloride forms of polyaniline in corrosion inhibition and (2) the ability of a polyaniline undercoat in providing corrosion protection by passivating the exposed metal surface. Here 350{Angstrom} and 70{Angstrom} thick Fe was sputter deposited onto the polyaniline and control polymer (non-electroactive) substrates and exposed to different environments. We conclude that an undercoat of the neutral emeraldine base form of polyaniline passivates the outer metal (Fe) surface with a thin ({approximately} 30-50{Angstrom}) oxide layer of mainly hematite (Fe{sub 2}O{sub 3}) and that the passivation mechanism has an electronic origin. In contrast, Fe sputtered onto doped emeraldine hydrochloride forms a thicker oxide layer with a distribution of oxidation states, effectively providing much less corrosion protection.
Characterization of the Discoidin Domain Receptor 2 Kinase as a Novel Therapeutic Target for Squamous Cell Lung Cancer (2012)

Abstract : This program has undertaken the study of the discoidin domain 2 (DDR2) tyrosine kinase as a potential therapeutic target in squamous cell lung cancer. We identified mutations in the DDR2 gene in a cohort of 290 individuals with this type of lung cancer and showed that these mutations are oncogenic when expressed in cell lines. Importantly, we showed that DDR2- driven cellular transformation sensitizes cancer cells to treatment with tyrosine kinase inhibitors which target DDR2, namely dasatinib. We have generated cellular and animals models to study DDR2, have studied the mechanisms by which DDR2 transforms cells and have worked to develop more selective inhibitors of DDR2 as well as identify mechanisms of cellular resistance to dasatinib therapy. This work has led to a publication in Cancer Discovery and has been presented at several scientific meetings including AACR and IASLC. Dasatinib is now being studied in the clinic as a DDR2 inhibitor in a national phase II trial for patients with squamous cell lung cancer, a disease for which no targeted agents are approved at this time.
Flavonoid‐mediated presenilin‐1 phosphorylation reduces Alzheimer's disease β‐amyloid production (2008)

Glycogen synthase kinase 3 (GSK-3) dysregulation is implicated in the two Alzheimer's disease (AD) pathological hallmarks: beta-amyloid plaques and neurofibrillary tangles. GSK-3 inhibitors may abrogate AD pathology by inhibiting amyloidogenic gamma-secretase cleavage of amyloid precursor protein (APP). Here, we report that the citrus bioflavonoid luteolin reduces amyloid-beta (Abeta) peptide generation in both human 'Swedish' mutant APP transgene-bearing neuron-like cells and primary neurons. We also find that luteolin induces changes consistent with GSK-3 inhibition that (i) decrease amyloidogenic gamma-secretase APP processing, and (ii) promote presenilin-1 (PS1) carboxyl-terminal fragment (CTF) phosphorylation. Importantly, we find GSK-3alpha activity is essential for both PS1 CTF phosphorylation and PS1-APP interaction. As validation of these findings in vivo, we find that luteolin, when applied to the Tg2576 mouse model of AD, decreases soluble Abeta levels, reduces GSK-3 activity, and disrupts PS1-APP association. In addition, we find that Tg2576 mice treated with diosmin, a glycoside of a flavonoid structurally similar to luteolin, display significantly reduced Abeta pathology. We suggest that GSK-3 inhibition is a viable therapeutic approach for AD by impacting PS1 phosphorylation-dependent regulation of amyloidogenesis.
Evolution of Host Cell RNA into Efficient Template RNA by Q.beta. Replicase: The Origin of RNA in Untemplated Reactions (1994)

Q beta replicase can replicate a single molecule of certain species of RNA to 10(14) copies in minutes. This replication ability has been used for in vitro studies of molecular evolution and is currently being utilized as a method of amplifying RNAs that contain probe sequences. It has been observed that Q beta replicase can produce replicatable RNA even in the absence of exogenously added template RNA. The origin of this RNA has been ascribed either to contamination with replicatable RNA or to an ability of Q beta replicase to synthesize RNA de novo from the nucleotides present in the reaction. Technologies that employ Q beta replicase require a thorough understanding of the conditions that lead to this so-called spontaneous RNA production. We have created an expression system and purification method with which we produce gram quantities of highly purified Q beta replicase, and we have identified reaction conditions that prevent the amplification of RNA in assays that do not contain added RNA. However, when these reaction conditions are relaxed, spontaneous RNA replication is seen in up to 100% of the assays. To understand the origin of this RNA, we have cloned several spontaneously produced RNAs. Sequence analysis of one of these RNAs shows that it arose by the evolution of Escherichia coli tRNA into a replicatable template and not by de novo synthesis from nucleoside triphosphates in the reaction.
Microwave Stethoscope, a new noninvasive multiple vital signs sensor: Human clinical trials (2012)

In this paper, preliminary human clinical trial results for the Microwave Stethoscope (MiSt) are presented. Benchmarking results using a Food and Drug Administration approved medical device, Propaq LT, have shown the feasibility of accurately detecting the heartbeat and respiration rates from a single measurement using the MiSt. Additionally and more importantly, the MiSt allows the non-invasive capturing of internal patient data such as the changes in the lung water content as well as the accurate heartbeat waveform that correlates very well with the electrocardiogram (ECG). All these encouraging results suggest that the MiSt has capabilities to monitor multiple vital signs including heart rate and respiration rate, and replace multiple sensors used to monitor heart rate and respiration rate.
Differentiating virulent 027 and non-027 Clostridium difficile strains by molecular methods (2015)

Objective: Hypervirulent Clostridium difficile clade has been shown to include several lineages of ribotype 027 and also other ribotypes. We present data on additional non-027 strains, identified as presumptive 027 by two commercial molecular C. difficile assays. Methods: The tested clinical isolates were selected from the national reference laboratory collection on the basis of toxin gene profile similarities with ribotype 027 and tested with Xpert®C. difficile/Epi and Amplidiag™ C. difficile+027 assay. Result: Xpert misclassified five ribotypes (016, 019, 080, 176 and variant of type 046) as presumptive 027 and Amplidiag two ribotypes (016, 176). The misclassified strains were rare, covering 1.6% of reference laboratory strain collection. Conclusion: Our findings confirm the concept that there are closely related outliers to hypervirulent 027 clones that can be misclassified as 027, and that these comprise numerous ribotypes, including previously reported four ribotypes (198, 176, 244, 019), and additio...
Relation of Lipoprotein Subclasses as Measured by Proton Nuclear Magnetic Resonance Spectroscopy to Coronary Artery Disease (1998)

Although each of the major lipoprotein fractions is composed of various subclasses that may differ in atherogenicity, the importance of this heterogeneity has been difficult to ascertain owing to the labor-intensive nature of subclass measurement methods. We have recently developed a procedure, using proton nuclear magnetic resonance (NMR) spectroscopy, to simultaneously quantify levels of subclasses of very low density (VLDL), low density (LDL), and high density (HDL) lipoproteins; subclass distributions determined with this method agree well with those derived by gradient gel electrophoresis. The objective of the current study of 158 men was to examine whether NMR-derived lipoprotein subclass levels improve the prediction of arteriographically documented coronary artery disease (CAD) when levels of lipids and lipoproteins are known. We found that a global measure of CAD severity was positively associated with levels of large VLDL and small HDL particles and inversely associated with intermediate size HDL particles; these associations were independent of age and standard lipid measurements. At comparable lipid and lipoprotein levels, for example, men with relatively high (higher than the median) levels of either small HDL or large VLDL particles were three to four times more likely to have extensive CAD than were the other men; the 27 men with high levels of both large VLDL and small HDL were 15 times more likely to have extensive CAD than were men with low levels. In contrast, adjustment for levels of triglycerides or HDL cholesterol greatly reduced the relation of small LDL particles to CAD. These findings suggest that large VLDL and small HDL particles may play important roles in the development of occlusive disease and that their measurement, which is not possible with routine lipid testing, may lead to more accurate risk assessment.
Characterization of bone quality using computer‐extracted radiographic features (1999)

Both bone mineral density (BMD) and trabecular structure are important determinates of bone mechanical properties. However, neither BMD or trabecular structural features can completely explain the variations in bone mechanical properties. In this study, we combine BMD and bone structural features to characterize bone mechanical behavior. Radiographs were obtained from 34 femoral neck specimens excised during total hip arthroplasties. Each neck radiograph was digitized and a region of interest (ROI) was selected from the medial side of the femoral neck. Textural features, the global Minkoswski dimension and trabecular orientation, were extracted from each ROI image using Minkowski dimension analysis. The BMD of each specimen was measured using dual-energy x-ray absorptiometry (DXA) and subsequently normalized by bone size as measured from a standard pelvis radiograph. Mechanical testing was performed on the trabecular bone cubes machined from each femoral neck to yield bone mechanical properties. Multiple regression was performed to select the best features to predict bone mechanical properties. The results suggest that, using multiple predictors including normalized BMD structural features, and patient age, the coefficients of determination (R2) improved over the use of BMD alone. For bone strength, the R2 was improved from 0.24 using conventional BMD to 0.48 using a four-predictor model. Similar results were obtained in the prediction of Young's modulus, i.e., the R2 was improved from 0.25 to 0.55 in going from the model using conventional BMD to a four-predictor model. This study demonstrates the contributions of normalized BMD, structural features, and age to bone mechanical properties, and suggests a potential method for the noninvasive evaluation of bone mechanical properties.
Nanoscale potential measurements in liquid by frequency modulation atomic force microscopy (2010)

We have developed a method for local potential measurements in liquid using frequency modulation atomic force microscopy. In this method, local potential is calculated from the first and second harmonic vibrations of a cantilever induced by applying an ac bias voltage between a tip and a sample. The use of an ac bias voltage with a relatively high frequency prevents uncontrolled electrochemical reactions and redistribution of ions and water. The nanoscale resolution of the method is demonstrated by imaging potential distribution of a dodecylamine thin film deposited on a graphite surface in 1 mM NaCl solution.
Separating Single-Walled Carbon Nanotubes by Length (2006)

Single-walled carbon nanotubes (SWNTs) are typically microns in length. However, intermediate lengths between small spheroidal fullerenes and long SWNTs could have significant scientific and technological importance in molecular electronics and sensing applications. Existing methods are limited by factors such as scalability, polydispersity and cost. Here we describe a simple, yet powerful technique for sorting SWNTs by length. It is based on a scalable two-phase liquid-liquid extraction process which is capable of transferring water-soluble SWNTs into an organic phase. The extraction utilizes electrostatic interactions between a common phase transfer agent and the sidewall functional groups on the nanotubes. Large length-dependent van der Waals forces for nanotubes allow the ability to control the length of nanotubes extracted into the organic phase as demonstrated by AFM.