gebhart/patrepeval huggingface dataset:
Development of a Scalable Synthesis of a Pyridinyl-3-azabicyclononene, a Novel Nicotinic Partial Agonist (2013)

The process research and development of two syntheses of a novel nicotinic partial agonist, TC-8817 ((+)-5), are described. The original Medicinal Chemistry route had multiple flaws, making it unsuitable for further development. A second approach was explored which was more amenable to optimization. The key steps were an intramolecular Lewis acid-promoted cyclization, a dibromination/elimination sequence to provide a vinyl bromide, and subsequent Suzuki coupling with 3-pyridineboronic acid. The overall yield of ∼3–16% over nine steps was offset by the low cost of goods and ease of synthesis. A major drawback was the need for simulated moving bed chiral separation on the penultimate intermediate to afford the subsequently desired single enantiomer version. A third-generation, asymmetric variation afforded a key intermediate in good yield and enantiomeric purity, providing proof of concept for a more efficient production of the desired (+)-enantiomer.
Electron Ionization Mass Spectrometry for Both Liquid and Gas Chromatography in One System without the Need for Hardware Adjustments (2020)

A new instrument that bridges the gap between gas chromatography (GC) and liquid chromatography (LC) mass spectrometry (MS) was developed. In this instrument GC–MS and electron ionization LC–MS were combined in one MS system with method based mode changing. The LC pneumatic spray formation interface to MS was mounted on top of an otherwise unused GC detector slot and was connected with a flow restriction capillary to the MS through the GC oven and into the MS transfer line, parallel to the GC capillary column. The LC output mobile phase flow is directed into a spray formation and vaporization chamber. The pneumatic spray results in fine spray droplets that are thermally vaporized at a pressure equal to or greater than ambient. A portion of the vaporized mixture is directed into the heated flow restriction capillary that connects the spray formation and vaporization chamber into the electron ionization (EI) ion source, while most of the vaporized spray is released to the atmosphere. The combined GC–MS and LC–MS system can work either with standard EI or with cold EI via interfacing the flow restriction capillary into a supersonic nozzle forming a supersonic molecular beam of a vibrationally cold sample compound. We found that EI–LC–MS with cold EI has many benefits when compared with standard EI. The EI–LC–MS interface can also serve for flow injection analysis. The performance of the combined system is demonstrated in the analysis of a few sample mixtures by both GC–MS and LC–MS analysis, sequentially without hardware adjustments.
Purification of Human Tissue-Type Plasminogen Activator in Centigram Quantities from Human Melanoma Cell Culture Fluid and Its Conditioning for Use In Vivo (1982)

Human tissue-type plasminogen activator was produced in centigram quantities from 50-60 1 batches of conditioned medium of a human melanoma cell culture. The yields of the procedure remained essentially unchanged during 50 subsequent preparations. The final products were of high purity as assessed by SDS gel electrophoresis. These materials, after filtration on 0.22 microM Milliporefilters were sterile and free of viruses and pyrogens. Their stability was very good in the fluid form at temperatures up to 56 degrees C. Material obtained by the present procedure has been used to investigate the biological and thrombolytic properties of tissue-type plasminogen activator.
Productivity Index Coupled with Drilling Risk Index: Application to Geosteering (2016)

Abstract Geosteering is a process used to optimize the positioning of a horizontal wellbore to maximize the reservoir exposure. Each wellbore design can vary greatly in terms of risk and complexity, which can have an impact on the final well performance. This paper proposes a novel methodology to identify an optimal well path, which minimizes the drilling risk and maximizes the productivity of the well based on its placement in the reservoir. The methodology presented uses a new comprehensive approach to calculate productivity index (PI) for a 3D wellbore. A new drilling risk index (RI) is proposed, which includes torque, drag, and trajectory risk factors. The torque and drag risk factors are normalized with respect to a base case trajectory, which can be selected based on field experience. In the present case, the authors selected a straight horizontal well as the base case. The trajectory risk factor is associated with the well profile energy, which is also normalized with a base case scenario. The final RI is the summation of the three individual risk indices. Applications of the methodology proposed are evaluated on a synthetic case in which a sensitivity analysis was performed on different possible well trajectories, and each trajectory was evaluated by comparing the proposed drilling risk and well productivity. The optimal trajectory is identified by differentiating the well productivity with RI among the low-risk trajectories to find the profile with maximum productivity. The well productivity is translated to revenue to highlight the commercial implications of the drilling project. The results demonstrate the trajectories with maximum reservoir exposure have a high risk associated, which can be translated into problems when running the completions. Neither the trajectory with the lowest risk nor the best performance is the optimum well trajectory. The authors also found that the dogleg distribution along the trajectory could have a significant impact on the RI and well productivity. The outcomes demonstrate usefulness of the approach in providing the engineer with a well path choice backed with good engineering approach on a real-time basis. This paper introduces a novel methodology to quantify the production and risk associated with different well trajectories while geosteering. To account for productivity estimation in complex undulated trajectories, a new comprehensive model is proposed. This is the first time both drilling and production parameters are considered in identifying an optimal well trajectory. The approach helps in placing the well in the sweet spot efficiently, which ultimately translates to revenue.
A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva (2006)

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G -> A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.
A New Kinetic Method for Assaying Serum 5′-Nucleotidase Using Nucleoside Oxidase (1989)

A sensitive kinetic determination of serum 5′-nucleotidase activity is described. Nucleoside oxidase catalyzes the oxidative coupling reaction of phenolic compounds and 4-aminoantipyrine to form colored substances in proportion of the amount of nucleoside. The present method relies on this phenomenon. Human serum 5′-nucleotidase was assayed using 5′-AMP as a substrate. When adenosine liberated was oxidized by nucleoside oxidase in the presence of phenolic compounds and 4-aminoantipyrine, a colored substance was formed at the same time. The rate of colored substance formation was proportional to the 5′-nucleotidase activity. The proposed method shows a low variation and a good correlation with the reference method. 3′-Nucleotidase was also assayed in a similar manner.
Semantic video object tracking using region-based classification (2002)

This paper introduces a novel semantic video object tracking system using backward region-based classification. It consists of five elementary steps: region pre-processing, region extraction, region-based motion estimation, region classification and region post-processing. Promising experimental results have shown solid performance of this generic tracking system with pixel-wise accuracy.
Impact of the SPOP Mutant Subtype on the Interpretation of Clinical Parameters in Prostate Cancer (2018)

Using a novel gene expression model and a decision tree algorithm to define prostate cancer molecular subclasses, we found that the <i>SPOP</i> mutant subclass is associated with higher preoperative PSA, less adverse pathologic features, and favorable prognosis. These findings suggest a paradigm in which the interpretation of common risk stratification parameters, particularly PSA, may be influenced by the underlying molecular subtype of prostate cancer.
Comparison of T Cell Activities Mediated by Human TCRs and CARs That Use the Same Recognition Domains (2017)

Adoptive T cell therapies have achieved significant clinical responses, especially in hematopoietic cancers. Two types of receptor systems have been used to redirect the activity of T cells, normal heterodimeric TCRs or synthetic chimeric Ag receptors (CARs). TCRs recognize peptide-HLA complexes whereas CARs typically use an Ab-derived single-chain fragments variable that recognizes cancer-associated cell-surface Ags. Although both receptors mediate diverse effector functions, a quantitative comparison of the sensitivity and signaling capacity of TCRs and CARs has been limited due to their differences in affinities and ligands. In this study we describe their direct comparison by using TCRs that could be formatted either as conventional αβ heterodimers, or as single-chain fragments variable constructs linked to CD3ζ and CD28 signaling domains or to CD3ζ alone. Two high-affinity TCRs (K<sub>D</sub> values of ∼50 and 250 nM) against MART1/HLA-A2 or WT1/HLA-A2 were used, allowing MART1 or WT1 peptide titrations to easily assess the impact of Ag density. Although CARs were expressed at higher surface levels than TCRs, they were 10-100-fold less sensitive, even in the absence of the CD8 coreceptor. Mathematical modeling demonstrated that lower CAR sensitivity could be attributed to less efficient signaling kinetics. Furthermore, reduced cytokine secretion observed at high Ag density for both TCRs and CARs suggested a role for negative regulators in both systems. Interestingly, at high Ag density, CARs also mediated greater maximal release of some cytokines, such as IL-2 and IL-6. These results have implications for the next-generation design of receptors used in adoptive T cell therapies.
A light weight car seat shaped by human body contour (2011)

The aim of this study is to develop a light-weight, comfortable seat. The idea is to shape a seat with a minimum of material by using the contour of the seated human. Twenty-five participants were asked to sit in a vacuum mattress placed on a wooden seat frame with similar angles as the car seat construction angles. They were instructed to sit in a comfortable position and perform driving movements. The mattress was then fixed, the contour scanned and digitised. All scans were superimposed giving input for a seat shell design made out of glass fibre laminate. The comfort experience of the shell was tested by 25 participants and compared with a standard BMW seat. The study shows that it is possible to create a rather comfortable seat using the human surface anatomy. However, more research on defining the specific form for the ideal shell is needed.
A new system for measurement of low frequency radio transmitting antenna parameters in near real time (1991)

A system that can be used to measure several important antenna and tuning system parameters on fixed-site very-low-frequency and low-frequency transmit antennas while the antennas are in normal operation is introduced. The measurements are made by sampling and processing the antenna voltage and current signals to calculate the antenna system resistance, capacitance, inductance, voltage, current, and power, which can be displayed and stored on a personal computer. All of the measurements are made while the antenna is being driven by FSK (frequency shift keying) or MSK (minimum shift keying) signals. A model of a typical low-frequency transmit antenna as well as the associated equations are presented. The response of the antenna system to FSK signals is presented. The algorithms, hardware, and software used by the measurement system, called the VLF/LF antenna monitor system (AMOS), are discussed along with a summary of results obtained during initial testing of the AMOS system. >
Phase Change Disc for High Data Rate Recording (2001)

We have developed a phase change disc having a thin transparent cover layer corresponding to the new optical recording system (DVR) using a blue laser (405 nm) and a numerical aperture (NA) of 0.85. We have achieved a user capacity of 22 GB per side of the 120 mm diameter disc, and a user data recording rate of 70 Mbps by designing a highly flat transparent cover layer, a recording layer having high crystallization speed and a film structure for rapid cooling.
RNA aptamers as effective protein antagonists in a multicellular organism (1999)

RNA aptamers selected against proteins can be used to modulate specific protein function. Expression of such reagents in cells and whole organisms could provide a means of dissecting and controlling molecular mechanisms in vivo. We demonstrate that Drosophila B52 protein can be specifically inhibited in vitro and in vivo by a multivalent RNA aptamer. This inhibitory aptamer RNA binds B52 avidly and inhibits B52-stimulated pre-mRNA splicing. It can be expressed in cultured cells and whole animals in a stable form that accumulates up to 10% of total mRNA. It binds B52 in vivo and suppresses all phenotypes caused by B52 overexpression. The strategies presented here should prove general in design and expression of functional and therapeutic RNAs.
Accurate New Solutions for Fluid Sample Contamination Quantification, With Special Focus on Water Sampling in Water-Base Mud (2016)

Abstract The role of formation testers has evolved significantly over the past decades. Early versions of this tool focused solely on obtaining pressure measurements and fluid samples. With advances in technology, the ability to measure fluid properties downhole at reservoir pressure and temperature has grown continuously. Today, formation tester downhole fluid analysis (DFA) and pressure measurements are routinely used to characterize fluids and address reservoir connectivity concerns in real time. However, quantitative use of fluid property measurements requires the user to measure—and correct for, as required—fluid contaminants caused by invaded mud filtrates. New measurements are combined with new algorithms to yield a harmonized contamination quantification solution that is applicable to all fluids and mud types. The quantification of drilling fluid content is at its most challenging when the formation fluids and drilling mud filtrate are fully miscible. Water-base mud (WBM) filtrate contamination measurement in formation water samples is particularly challenging because formation water and WBM filtrate exhibit very similar near-infrared optical spectroscopy signatures and are therefore difficult to differentiate. Native and invaded fluid typically do have measurably different live fluid density or resistivity. However, resistivity measurements should only be used if a temperature correction is applied. The general workflow for real-time hydrocarbon contamination quantification in oil-base mud (OBM) has been applied to water sampling in WBM, using live fluid density and resistivity measurements. First, a temperature correction is applied to the resistivity measurement and the data are converted to conductivity. Next, density- and temperature-corrected conductivity data are crossplotted and a novel linear relation is generated. The independently determined filtrate and formation water properties (endpoints) should fall on the extrapolated linear relation because this relation is intrinsic to the fluid mixture. Lastly, the fluid mixture measurements and endpoints are entered into mixing rules to calculate contamination. With this new method for quantifying water sample contamination, there is now a complete solution that is applicable to all fluid combinations. Several case studies of water sampling in WBM show the effectiveness of the new mud filtrate contamination quantification method.
Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients (2017)

<b>Purpose:</b> Older acute myeloid leukemia (AML) patients have a poor prognosis; therefore, novel therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. Here, we report the first-in-human study exploiting a unique scalable NK-cell product generated <i>ex vivo</i> from CD34<sup>+</sup> hematopoietic stem and progenitor cells (HSPC) from partially HLA-matched umbilical cord blood units.<b>Experimental Design:</b> Ten older AML patients in morphologic complete remission received an escalating HSPC-NK cell dose (between 3 and 30 × 10<sup>6</sup>/kg body weight) after lymphodepleting chemotherapy without cytokine boosting.<b>Results:</b> HSPC-NK cell products contained a median of 75% highly activated NK cells, with <1 × 10<sup>4</sup> T cells/kg and <3 × 10<sup>5</sup> B cells/kg body weight. HSPC-NK cells were well tolerated, and neither graft-versus-host disease nor toxicity was observed. Despite no cytokine boosting being given, transient HSPC-NK cell persistence was clearly found in peripheral blood up to 21% until day 8, which was accompanied by augmented IL15 plasma levels. Moreover, donor chimerism up to 3.5% was found in bone marrow. Interestingly, <i>in vivo</i> HSPC-NK cell maturation was observed, indicated by the rapid acquisition of CD16 and KIR expression, while expression of most activating receptors was sustained. Notably, 2 of 4 patients with minimal residual disease (MRD) in bone marrow before infusion became MRD negative (<0.1%), which lasted for 6 months.<b>Conclusions:</b> These findings indicate that HSPC-NK cell adoptive transfer is a promising, potential "off-the-shelf" translational immunotherapy approach in AML. <i>Clin Cancer Res; 23(15); 4107-18. ©2017 AACR</i>.
Thermochemical decomposition of water catalyzed by zeolites (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThermochemical decomposition of water catalyzed by zeolitesPaul H. Kasai and Roland J. Bishop Jr.Cite this: J. Phys. Chem. 1977, 81, 15, 1527–1529Publication Date (Print):July 1, 1977Publication History Published online1 May 2002Published inissue 1 July 1977https://pubs.acs.org/doi/10.1021/j100530a023https://doi.org/10.1021/j100530a023research-articleACS PublicationsRequest reuse permissionsArticle Views162Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Measurement of polarization mode dispersion (1994)

Polarization mode dispersion is a fundamental characteristic of optical components and fibers, but its elegant simplicity is often hidden in reports of new results. This tutorial begins with a simple description of polarization mode dispersion and its physical effects, and explores some of the resulting characteristics of optical fiber transmission links and devices. The capabilities and limitations of a variety of polarization mode dispersion measurement techniques are discussed and compared, with special attention paid to measurement by wavelength scanning, interferometry, and Jones matrix eigenanalysis. Results of measurements by the different techniques are directly compared for a variety of optical test devices.
Design and Fabrication of Gecko-Inspired Adhesives (2012)

Recently, there has been significant interest in developing dry adhesives mimicking the gecko adhesive system, which offers several advantages compared to conventional pressure-sensitive adhesives. Specifically, gecko adhesive pads have anisotropic adhesion properties; the adhesive pads (spatulae) stick strongly when sheared in one direction but are non-adherent when sheared in the opposite direction. This anisotropy property is attributed to the complex topography of the array of fine tilted and curved columnar structures (setae) that bear the spatulae. In this study, we present an easy, scalable method, relying on conventional and unconventional techniques, to incorporate tilt in the fabrication of synthetic polymer-based dry adhesives mimicking the gecko adhesive system, which provides anisotropic adhesion properties. We measured the anisotropic adhesion and friction properties of samples with various tilt angles to test the validity of a nanoscale tape-peeling model of spatular function. Consistent with the peel zone model, samples with lower tilt angles yielded larger adhesion forces. The tribological properties of the synthetic arrays were highly anisotropic, reminiscent of the frictional adhesion behavior of gecko setal arrays. When a 60° tilt sample was actuated in the gripping direction, a static adhesion strength of ~1.4 N/cm(2) and a static friction strength of ~5.4 N/cm(2) were obtained. In contrast, when the dry adhesive was actuated in the releasing direction, we measured an initial repulsive normal force and negligible friction.