gebhart/patrepeval huggingface dataset:
A two-part, phase II, multi-center study of the ERK inhibitor ulixertinib (BVD-523) for patients with advanced malignancies harboring MEK or atypical BRAF alterations (BVD-523-ABC). (2022)

TPS3172 Background: Ulixertinib (BVD-523) is a small molecule inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2) in development as a novel anti-cancer drug. Early clinical data demonstrated anti-tumor activity, especially for patients with tumors harboring atypical BRAF or MEK1/2 alterations (Sullivan et al., Cancer Discov. 2018;8(2):184-195). Atypical BRAF (non-V600) alterations can be categorized according to characteristics of molecular signaling (Class II or III), are seen in approximately 3% of all human cancers, and there are currently no approved therapies for this indication. Similar to atypical BRAF alterations, the incidence of MEK1/2 alterations are rare in human tumors (&lt; 1 %). Preclinical data have demonstrated activity of ulixertinib in MEK mutant models. Ulixertinib has FDA fast-track designation for patients with solid tumors, other than CRC, with specific BRAF mutations (G469A, L485W, or L597Q). Designed with intent to register, the BVD-523-ABC clinical trial will continue evaluation of ulixertinib in patients with tumors harboring any atypical BRAF or MEK1/2 alteration (NCT04488003). Methods: This multi-center, phase II study, will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib in patients with advanced malignancies. Ulixertinib will be administered at the RP2D of 600 mg BID for 28-day treatment cycles. Eligible patients will have locally advanced or metastatic cancer which progressed following standard systemic therapies, or for which the patient is not a candidate or refused systemic therapy. Planned correlative analyses include reverse phase protein array and transcriptomics of tumor tissue. Part A is open-label and tumor agnostic, except for group 4 and 6 (CRC patients only). Patients will enroll into one of six groups based on BRAF (groups 1-4) or MEK1/2 (groups 5-6) tumor alteration (38 patients per group). Overall response rate (ORR) is the primary endpoint for Part A, with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Part B is tumor histology specific. Patients will be randomized to receive either ulixertinib or physician's choice of treatment in a 2:1 ratio. Up to three specified tumor histologies will be defined, guided by available Part A data (n = 80-100 per histology). The primary endpoint of Part B is PFS, and secondary endpoints include OS, ORR, and DOR. This study has enrolled 43 patients of the planned 228 in Part A at the time of abstract submission. Clinical trial information: NCT04488003.
Next Generation MUT-MAP, a High-Sensitivity High-Throughput Microfluidics Chip-Based Mutation Analysis Panel (2014)

Molecular profiling of tumor tissue to detect alterations, such as oncogenic mutations, plays a vital role in determining treatment options in oncology. Hence, there is an increasing need for a robust and high-throughput technology to detect oncogenic hotspot mutations. Although commercial assays are available to detect genetic alterations in single genes, only a limited amount of tissue is often available from patients, requiring multiplexing to allow for simultaneous detection of mutations in many genes using low DNA input. Even though next-generation sequencing (NGS) platforms provide powerful tools for this purpose, they face challenges such as high cost, large DNA input requirement, complex data analysis, and long turnaround times, limiting their use in clinical settings. We report the development of the next generation mutation multi-analyte panel (MUT-MAP), a high-throughput microfluidic, panel for detecting 120 somatic mutations across eleven genes of therapeutic interest (AKT1, BRAF, EGFR, FGFR3, FLT3, HRAS, KIT, KRAS, MET, NRAS, and PIK3CA) using allele-specific PCR (AS-PCR) and Taqman technology. This mutation panel requires as little as 2 ng of high quality DNA from fresh frozen or 100 ng of DNA from formalin-fixed paraffin-embedded (FFPE) tissues. Mutation calls, including an automated data analysis process, have been implemented to run 88 samples per day. Validation of this platform using plasmids showed robust signal and low cross-reactivity in all of the newly added assays and mutation calls in cell line samples were found to be consistent with the Catalogue of Somatic Mutations in Cancer (COSMIC) database allowing for direct comparison of our platform to Sanger sequencing. High correlation with NGS when compared to the SuraSeq500 panel run on the Ion Torrent platform in a FFPE dilution experiment showed assay sensitivity down to 0.45%. This multiplexed mutation panel is a valuable tool for high-throughput biomarker discovery in personalized medicine and cancer drug development.
Removal of Propylene from Fuel‐Grade Propane (2004)

Abstract Propane produced in refinery operations often contains substantial amounts of propylene. Propylene may cause problems through engine and injector deposits when propane is used as a motor fuel. Also, propylene is capable of polymerizing in storage, fuel lines, or vaporizers, and thus may cause plugging by gum deposits. As the use of propane expands into the motor fuel and other new markets, the removal of propylene will become increasingly more important. This manuscript reviews the most promising technologies for removal of propylene from refinery‐derived propane. The only current commercially‐practiced approaches are distillation and catalytic hydrogenation. Distillation is a viable technology for removal of propylene from propane, but both capital and energy costs are high, due to the very low relative volatility between the two species. Catalytic hydrogenation is straightforward, but also has a high capital cost, and the cost/availability of the continuous hydrogen production required may also be problematic. Two other approaches are very near commercialization: (1) absorption/stripping based on aqueous silver nitrate solution, and (2) pressure‐swing adsorption based on zeolite molecular sieves. Membranes also show promise to provide in a single stage separation equivalent to many stages of distillation, with simple, compact, and robust equipment. Chemically selective sorbents offer even higher degrees of separation in a single stage, albeit in more complex equipment.
Glossopharyngeal neuralgia associated with vascular compression and choroid plexus papilloma (1995)

We report two cases of presumed idiopathic glossopharyngeal neuralgia that were discovered intraoperatively to be associated with compression by choroid plexus papillomas, and by a variable degree of vascular compression at the root entry zones of cranial nerves IX and X. The combination of the two entities in glossopharyngeal neuralgia has not previously been reported.
A MICROFLUIDIC PLATFORM FOR SCREENING AND SELECTION OF MONOCLONAL ANTIBODIES FROM SINGLE CELLS (2011)

We report a microfluidic platform for rapid screening and selection of monoclonal antibodies (mAbs) secreted by single cells. The microfluidic platform integrates single-cell handling and compartmentalization, fluorescence detection of antibod- ies secreted by cells, and cell recovery for reverse transcription polymerase chain reaction (RT-PCR) of antibody genes. 5 antibody-secreting cells, a typical fusion will yield less than 100 viable hybrid- omas. Therefore, fusions from tens to hundreds of animals are required to fully sample the antibody diversity produced in an immune response, making the hybridoma approach both time-consuming and expensive. As every antibody-producing cell (ASC) in the vertebrate immune system can produce a unique antibody, ASCs are an ideal system for single-cell analysis. Recently, antibodies have been selected from single cells without clonal expansion.(3) ASCs are harvested from immunized animals and monoclonal antibodies are produced by single-cell reverse-transcription polymerase chain reaction (RT-PCR) of antibody genes, followed by cloning and expression of these genes. Subsequently, all antibody genes are cloned and expressed in order to select antigen-specific mAbs, thereby making these single-cell techniques similarly expensive and time-consuming to other approaches requiring clonal expansion. We hypothesized that, by compart- mentalizing single cells in micro-fabricated wells 10 3 times smaller in volume ( 1µL), we could screen and select antibodies produced by single cells for their affinity and selectivity to target antigens. As ASCs are known to produce antibodies at a very high rate (1000s of molecules per second), they secrete detectable concentra- tions (>1nM) of antibodies within hours of incubation in a sub-nanoliter chamber. In contrast, in conventional 96-well plates, primary ASCs need to be cultured for up to one week in order to obtain detectable antibody concentrations; however, these cells cannot be efficiently cultured in laboratory conditions for longer than 1 day. Previous studies have shown that antibod- ies secreted by single cells can be detected in microfabricated sub-nanoliter wells using fluorescence microscopy. (4-5) We have developed a novel microfluidic technology for rapid screening and selection of monoclonal antibodies from single anti- body-secreting cells without clonal expansion. The microfluidic platform integrates the handling and compartmentalization of single cells, fluorescence measurements of antigen binding kinetics of antibodies secreted by single cells, and recovery of se- lected cells for off-chip reverse transcription polymerase chain reaction (RT-PCR) of antibody genes. THEORY
Plasma Levels and Analgesia Following Deltoid and Gluteal Injections of Methadone and Morphine (1984)

GRABINSKI, P. Y.; KAIKO, R. F.; ROGERS, A. G.; HOUDE, R. W.; Wyant, Gordon M. M.D. Author Information
Bringing Salary Transparency to the World (2017)

The recently launched LinkedIn Salary product has been designed with the goal of providing compensation insights to the world's professionals and thereby helping them optimize their earning potential. We describe the overall design and architecture of the statistical modeling system underlying this product. We focus on the unique data mining challenges while designing and implementing the system, and describe the modeling components such as Bayesian hierarchical smoothing that help to compute and present robust compensation insights to users. We report on extensive evaluation with nearly one year of de-identified compensation data collected from over one million LinkedIn users, thereby demonstrating the efficacy of the statistical models. We also highlight the lessons learned through the deployment of our system at LinkedIn.
Antitumor activity of XR5944, a novel and potent topoisomerase poison (2001)

Inhibitors of topoisomerases are widely used in the treatment of cancer, including inhibitors of topoisomerase I (camptothecin analogs such as irinotecan and topotecan) and topoisomerase II (etoposide and doxorubicin). The novel bis-phenazine, XR5944, is a joint inhibitor of topoisomerase I and II as shown by the stabilization of topoisomerase-dependent cleavable complexes. XR5944 demonstrated exceptional activity against human and murine tumor cells in vitro and in vivo. In a range of cell lines XR5944 (IC50 0.04-0.4 nM) was significantly more potent than TAS-103, originally proposed as a joint topoisomerase I and II inhibitor, as well as agents specific for topoisomerase I or II (topotecan, doxorubicin and etoposide). In addition, XR5944 was unaffected by atypical drug resistance and retained significant activity in cells overexpressing P-glycoprotein or multidrug resistance-associated protein. Antitumor efficacy of XR5944 was demonstrated in human carcinoma xenograft models (H69 small cell lung cancer and HT29 colon). In the HT29 model, which is relatively unresponsive to chemotherapy, XR5944 (15 mg/kg i.v., q4dx3) induced tumor regression in the majority of animals (six of eight), whereas TAS-103, dosed at its maximum tolerated dose (45 mg/kg i.v., q7dx3), only induced a delay in tumor growth compared with control animals. In the H69 model, low doses of XR5944 (5 mg/kg i.v., qdx5/week for 2 weeks or 10-15 mg/kg i.v., q4dx3), induced complete tumor regression in the majority of animals. In contrast, topotecan (20 mg/kg i.v., q4dx3) or etoposide (30 mg/kg i.v., q5dx5) only slowed the tumor growth rate. These studies show that XR5944 is a highly active novel anticancer agent that is well tolerated at efficacious doses.
On the Robustness of the Superdirective Beamformer (2021)

In microphone array beamforming, a high directional gain is always desired for acoustic noise and reverberation suppression; as a result, the superdirective beamformer has been of great interest in many applications. However, this beamformer is well known to be very sensitive to array imperfections. While much effort has been made to improve its robustness, it is still a major problem. This paper is essentially devoted to the study of the robustness of the superdirective beamformer and derivation of better ways to deal with this important issue. We first prove that any distortionless fixed beamformer can be written as the sum of two orthogonal beamformers, i.e., the sum of the classical delay-and-sum (DS) beamformer and a reduced-rank beamformer. Based on this property, different kinds of robust superdirective beamformers are then developed. We also show that the robust design problem can be transformed into a quadratic eigenvalue problem (QEP), which leads to a solution that achieves the maximum possible directivity factor (DF) while meets the white noise gain (WNG) constraint over a frequency band of interest.
Speckle effects in adaptive optical systems (1984)

An analysis is made of the influence of accidental speckle modulation on the operation of adaptive systems. Methods are suggested for adaptive focusing in the presence of a highly developed speckle structure of the field scattered by a rough surface. These methods are based on an analysis of the statistics of the received signal. The results are reported of model experiments on an adaptive system for radiation focusing on the basis of statistical criteria.
<title>Real-time detection of airborne chemicals</title> (1999)

Accurate, real time air quality measurements are difficult to make, because real time sensors for some gas species are not specific to a single gas. For example, some carbon dioxide sensors react to hydrogen sulfide. By combining the response of several types of real time gas sensors the Real-time Air Quality Monitoring System (RAQMS) accurately measures many different gases. The sensor suite for the INEEL's Real-time Air Quality Monitoring System (RAQMS) incudes seven, inexpensive, commercially-available chemical sensors for gases associated with air quality. These chemical sensors are marketed as devices to measure carbon dioxide, hydrogen sulfide, carbon monoxide, sulfur dioxide, nitrogen dioxide, water vapor and volatile organic compounds (VOC's). However, these chemical sensors respond to more than a single compound, e.g. both the VOC and the carbon dioxide sensors respond strongly to methane. This multiple sensor response to a given chemical is used to advantage in the RAQMS system, as patterns of responses by the sensors were found to be unique and distinguishable for several chemicals. Therefore, there is the potential that the seven sensors combined output can: (1) provide more accurate measurements of the advertized gases and (2) estimate the presence and quantity of additional gases. The patterns of sensor response can be thought of as clusters of data points in a seven dimensional space. One dimension for each sensor's output. For all of the gases tested, these clusters were separated enough that good quantitative results were obtained. As an example, the prototype RAQMS is able to distinguish methane from butane and predict accurate concentrations of both gases. A mathematical technique for estimating probability density functions from random samples is used to distinguish the data clusters from each other and to make gas concentration estimates. Bayes optimal estimates of gas concentration are calculated using the probability density function. The Bayes optimal estimates are analogous to least square error curve fits or regression analysis. A computer program was used to find the best parameters for the Bayes optimal estimating functions. The program implemented a probabilistic neural net.
Iterative trace reconstruction of aliased RF data obtained using harmonic imaging: A feasibility study (2017)

It is critical to use a proper spatial sampling, otherwise images suffer from grating lobes. However, the cost of a medical ultrasound scanner is strongly related to the channel count of the receive electronics. This has led to channel reduction using multiplexing or in-probe pre-beamforming methods at the cost of image quality or frame rate. An alternative is to reduce the receive channel count and reconstruct the non-aliased data from spatially aliased data. Last year we reported on a wavenumber frequency domain mapping (Stolt migration) based iterative trace reconstruction method developed for fundamental imaging. However, harmonic imaging is often used in medical imaging to further improve the image quality. Here, the feasibility of using the method for harmonic imaging is investigated using in-vitro and in-vivo linear array data.
ELISA-Based Assay for Studying Major and Minor Group Rhinovirus–Receptor Interactions (2020)

Rhinovirus (RV) infections are a major cause of recurrent common colds and trigger severe exacerbations of chronic respiratory diseases. Major challenges for the development of vaccines for RV include the virus occurring in the form of approximately 160 different serotypes, using different receptors, and the need for preclinical models for the screening of vaccine candidates and antiviral compounds. We report the establishment and characterization of an ELISA-based assay for studying major and minor group RV-receptor interactions. This assay is based on the interaction of purified virus with plate-bound human receptor proteins, intercellular adhesion molecule 1 (ICAM-1), and low density lipoprotein receptor (LDLR). Using RV strain-specific antibodies, we demonstrate the specific binding of a panel of major and minor RV group types including RV-A and RV-B strains to ICAM-1 and LDLR, respectively. We show that the RV-receptor interaction can be blocked with receptor-specific antibodies as well as with soluble receptors and neutralizing RV-specific antibodies. The assay is more sensitive than a cell culture-based virus neutralization test. The ELISA assay will therefore be useful for the preclinical evaluation for preventive and therapeutic strategies targeting the RV-receptor interaction, such as vaccines, antibodies, and anti-viral compounds.
Central limit theorems for network driven sampling (2017)

Respondent-Driven Sampling is a popular technique for sampling hidden populations. This paper models Respondent-Driven Sampling as a Markov process indexed by a tree. Our main results show that the Volz-Heckathorn estimator is asymptotically normal below a critical threshold. The key technical difficulties stem from (i) the dependence between samples and (ii) the tree structure which characterizes the dependence. The theorems allow the growth rate of the tree to exceed one and suggest that this growth rate should not be too large.
Reconstructing the prevailing meteorological and optical environment during the time of the Titanic disaster (2014)

In this paper, we reconstruct the meteorological and optical environment during the time of Titanic’s disaster utilizing a state-of-the-art meteorological model, a ray-tracing code, and a unique public-domain dataset called the Twentieth Century Global Reanalysis. With high fidelity, our simulation captured the occurrence of an unusually high Arctic pressure system over the disaster site with calm wind. It also reproduced the movement of a polar cold front through the region bringing a rapid drop in air temperature. The simulated results also suggest that unusual meteorological conditions persisted several hours prior to the Titanic disaster which contributed to super-refraction and intermittent optical turbulence. However, according to the simulations, such anomalous conditions were not present at the time of the collision of Titanic with an iceberg.
Targeting transforming growth factor beta to enhance cancer immunotherapy. (2006)

Richard J. Ablin, phd, Research Professor of Immunobiology, University of Arizona College of Medicine and the Arizona Cancer Center, Tucson, Arizona, U.S.A., and Phil Gold, phd, md, Professor of Medicine, Physiology, and Oncology, McGill University, Montreal, Quebec, Canada, Section Editors.
Quantitative Evaluation of Lewis Acidity of Metal Ions with Different Ligands and Counterions in Relation to the Promoting Effects of Lewis Acids on Electron Transfer Reduction of Oxygen (2003)

The g(zz) values of ESR spectra of superoxide (O(2)(.-) complexes of metal ion salts acting as Lewis acids with different ligands and counterions were determined in acetonitrile at 143 K. The binding energies (DeltaE) of (O(2)(.-)/Lewis acid complexes have been evaluated from deviation of the g(zz) values from the free spin value. The DeltaE value is quite sensitive to the difference in the counterions and ligands of metal ion salts acting as Lewis acids. On the other hand, the fluorescence maxima of the singlet excited states of 10-methylacridone/Lewis acid complexes are red-shifted as compared with that of 10-methylacridone, and the relative emission energies (Deltahnu(f)) vary significantly depending on the Lewis acidity of metal ion salts with different counterions and ligands. The promoting effects of Lewis acids were also examined on electron transfer from cobalt(II) tetraphenylporphyrin to oxygen in acetonitrile at 298 K, which does not occur in the absence of Lewis acids under otherwise the same experimental conditions. Both DeltaE and Deltahnu(f) values are well correlated with the promoting effects of Lewis acids on the electron transfer reduction of oxygen. Such correlations indicate that DeltaE and Deltahnu(f) values can be used as quantitative measures of Lewis acidity of metal ion salts with different ligands and counterions. The Lewis acidity thus determined can also be applied to predict the promoting effects of Lewis acids on organic synthesis.
Strictly alternating copolymers containing parabanic acid and amide or imide moieties (1987)

Abstract 1,3‐Bis(4‐aminophenyl)imidazolidinetrione dihydrochloride ( 1 ) was synthesized and used as starting material for the synthesis of strictly alternating copolymers. Fully aromatic copolymers containing parabanic acid and amide moieties ( 7a, b ) were found to exhibit high glass temperatures and good thermal stability. Meltable copolymers with parabanic acid and amide moieties ( 7d–j ) could be obtained by introducing flexible aliphatic spacers. The use of an unusually short, but symmetrically branched spacer was particularly effective. The strictly alternating, thermally stable copolymer 10 was synthesized from 1 and pyromellitic dianhydride. By using the trimethylsilyl ester of polyamic acid 11 , the imidization temperature could be lowered by 100°C.