gebhart/patrepeval huggingface dataset:
The Challenges and Concerns Companies Face Pertaining to the US Food and Drug Administration 510(k) Process for Cardiac Biomarkers (2011)

Cardiac troponins I (cTnI)8 and T (cTnT) have been internationally recognized as the standard biomarkers for the detection of myocardial injury, the diagnosis of myocardial infarction (MI), and risk stratification of patients presenting with symptoms of acute coronary syndrome (ACS). Laboratory medicine, cardiology, and emergency medicine organizations have endorsed the use of the 99th-percentile troponin value, which is derived from a reference population, as the medical decision-making cutpoint. From the time of the first US Food and Drug Administration (FDA) clearance of cTnT in 1995 through 2010, the FDA-cleared cTnT and CTnI assays were predicated on the ROC curve–derived cutpoint optimized for diagnostic sensitivity and specificity. The PATHFAST cTnI assay introduced by Mitsubishi in 2001 is apparently the first assay cleared by the FDA on the basis of the 99th-percentile value that aids in the diagnosis of MI. With the growing literature describing multiple research high-sensitivity cTnI (hs-cTnI) assays and an hs-cTnT assay (marketed outside the US, not FDA cleared), manufacturers are facing new challenges in bringing to market these new assays that use the 99th percentile as the cutpoint value for medical decisions. Several leaders in the in vitro diagnostics industry have been asked to give their views on important issues that affect laboratory scientists and clinicians.

On April 30, 2010, the FDA issued a “Points to Consider” paper providing an overview of both analytical- and clinical-performance expectations for assays that are to be submitted for 510(k) clearance on the basis of the 99th-percentile cutoff. What do you see as the major analytical and clinical challenges presented by this document? 

David Hickey: We at Siemens realize that the utility of troponin assays has evolved, and we understand that our methods of validating the performance of new troponin assays must also evolve. Some of the analytical and clinical challenges …
Mechanistic and Metabolic Inferences from the Binding of Substrate Analogues and Products to Arginase, (2001)

Arginase is a binuclear Mn(2+) metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea. X-ray crystal structures of arginase complexed to substrate analogues N(omega)-hydroxy-L-arginine and N(omega)-hydroxy-nor-L-arginine, as well as the products L-ornithine and urea, complete a set of structural "snapshots" along the reaction coordinate of arginase catalysis when interpreted along with the X-ray crystal structure of the arginase-transition-state analogue complex described in Kim et al. [Kim, N. N., Cox, J. D., Baggio, R. F., Emig, F. A., Mistry, S., Harper, S. L., Speicher, D. W., Morris, Jr., S. M., Ash, D. E., Traish, A. M., and Christianson, D. W. (2001) Biochemistry 40, 2678-2688]. Taken together, these structures render important insight on the structural determinants of tight binding inhibitors. Furthermore, we demonstrate for the first time the structural mechanistic link between arginase and NO synthase through their respective complexes with N(omega)-hydroxy-L-arginine. That N(omega)-hydroxy-L-arginine is a catalytic intermediate for NO synthase and an inhibitor of arginase reflects the reciprocal metabolic relationship between these two critical enzymes of L-arginine catabolism.
Novel molecular approaches to cystic fibrosis gene therapy (2005)

Gene therapy holds promise for the treatment of a range of inherited diseases, such as cystic fibrosis. However, efficient delivery and expression of the therapeutic transgene at levels sufficient to result in phenotypic correction of cystic fibrosis pulmonary disease has proved elusive. There are many reasons for this lack of progress, both macroscopically in terms of airway defence mechanisms and at the molecular level with regard to effective cDNA delivery. This review of approaches to cystic fibrosis gene therapy covers these areas in detail and highlights recent progress in the field. For gene therapy to be effective in patients with cystic fibrosis, the cDNA encoding the cystic fibrosis transmembrane conductance regulator protein must be delivered effectively to the nucleus of the epithelial cells lining the bronchial tree within the lungs. Expression of the transgene must be maintained at adequate levels for the lifetime of the patient, either by repeat dosage of the vector or by targeting airway stem cells. Clinical trials of gene therapy for cystic fibrosis have demonstrated proof of principle, but gene expression has been limited to 30 days at best. Results suggest that viral vectors such as adenovirus and adeno-associated virus are unsuited to repeat dosing, as the immune response reduces the effectiveness of each subsequent dose. Nonviral approaches, such as cationic liposomes, appear more suited to repeat dosing, but have been less effective. Current work regarding non-viral gene delivery is now focused on understanding the mechanisms involved in cell entry, endosomal escape and nuclear import of the transgene. There is now increasing evidence to suggest that additional ligands that facilitate endosomal escape or contain a nuclear localization signal may enhance liposome-mediated gene delivery. Much progress in this area has been informed by advances in our understanding of the mechanisms by which viruses deliver their genomes to the nuclei of host cells.
A Method for Coil Design of Superconducting Quadrupoles Based on Sector Coils and Fourier Series (2010)

In this paper we present a novel method to optimize quadrupole coil cross-sections based on the cos 2¿-type. We first approximate real coil blocks made of cables with concentric sectors powered with a constant current density to make use of analytical expressions of the magnetic field based on the Fourier series development. This allows a rapid evaluation of the field harmonics which permits an almost exhaustive scan on sectors position and dimensions for coil layouts made of up to five sectors. The coil layouts having a larger short-sample gradient can be further explored, approximating them with blocks of Rutherford cables. This second step requires a second fine tuning of the cross-section around the previously found optimum. The method has been used to design a proposed coil cross-section for the new inner triplet quadrupole for the LHC.
Considering species richness and rarity when selecting optimal survey traps: comparisons of semiochemical baited flight intercept traps for Cerambycidae in eastern North America (2014)

Abstract We compared standard multiple‐funnel, modified multiple‐funnel, intercept panel and canopy malaise ( SLAM ) traps with top and bottom collecting cups for their effectiveness (species richness, rarity, abundance) at capturing Cerambycidae in eastern North America. Experiments were conducted in New York, Louisiana, Massachusetts and Georgia in 2011 and 2012. A combination of pheromones and host volatiles chosen to match local forest types were used as lures. Species richness tended to be higher in SLAM and modified funnel traps than standard funnel and intercept panel traps. SLAM traps also captured the highest number of species, unique species, rare (species accounting for ≤ 1% of total cerambycids at a site) and singleton species at each site. Individual‐based rarefaction and sample‐based species accumulation curves suggested that SLAM traps are more effective for capturing cerambycid species. For many estimates, modified funnel and funnel traps were lower than SLAM traps but greater than intercept panel traps for describing cerambycid communities. Modified funnel and SLAM traps generally captured the highest abundance of cerambycids but the response of the individual subfamily and species varied by trap type. SLAM traps should be considered as a strong tool to describe cerambycid communities when used in conjunction with pheromones and host volatiles.
Decoupled Water Splitting: From Basic Science to Application (2020)

In this review, we discuss disruptive decoupled water splitting schemes, in which the concurrent production of hydrogen and oxygen in close proximity to each other in conventional electrolysis is replaced by time- or space-separated hydrogen and oxygen production steps. We present the main decoupling strategies, including electrolytic and electrochemical chemical water splitting cycles, and the redox materials that facilitate them by mediating the ion exchange between the hydrogen and oxygen evolution reactions. Decoupled water splitting offers increased flexibility and robustness and provides new opportunities for hydrogen production from renewable sources.
Towards a Generic Methodology to Model Solar Thermal Systems using Neural Networks Through a Short Dynamic Test (2015)

International audience
Investigation on proximity-coupled microstrip integrated PV antenna (2007)

The use of polycrystalline silicon solar cells (156 ×156 mm) as a groundplane for a proximity-coupled microstrip square patch antenna (30 × 30 mm) is investigated. Four different models that arise from the different possible positions of the cell with respect to patch, were simulated, fabricated and compared to an ideal PEC ground plane antenna of the same size. It was found that the use of the solar cell as ground plane is feasible, yielding similar impedance bandwidth (around 4%, 3.5% for the PEC) with reasonable gain. The feasibility of using poly-crystalline solar cells as a ground plane, instead of a PEC is examined for proximity coupled patch antennas. (3 pages)
Einführung in die Immobilienwirtschaft (2001)

Die Immobilienbetriebslehre ist im Vergleich zur allgemeinen Betriebswirtschaftslehre und zu einer Reihe spezieller Betriebswirtschaftslehren, wie z.B. der Bankbetriebslehre oder der Handelsbetriebslehre eine relativ junge Wirtschafts- und Wissenschaftsdisziplin. Hieraus ergibt sich zunächst die Notwendigkeit, eine inhaltliche Bestimmung der Immobilienwirtschaft vorzunehmen.
Is carotid intima media thickness useful for individual prediction of cardiovascular risk? Ten-year results from the Carotid Atherosclerosis Progression Study (CAPS) (2010)

Despite cIMT being predictive for cardiovascular endpoints, it did not consistently improve the risk classification of individuals. Carotid intima media thickness may not be useful for the risk stratification of individuals in the general population.
Novel magnetic characterization of the head-medium interface in metal particle tape systems (2001)

The head-medium noise of modern metal particle tape systems, which results from spacing fluctuations during the recording of data, dominates the medium noise of today's advanced digital tape. Traditionally, characterization of the head-medium interface has been performed by using interferometry or AFM measurements of the tape surface roughness. However, surface roughness measurements on two advanced metal particle tape media displayed no correlation with the tape medium noise characteristics. A new insight into the impact of the tape load-bearing surface distribution on the head-tape spacing variation explained the shortcomings of the roughness measurements to gauge the medium noise. Assessing the performance and characteristics of the head-medium interface requires a new methodology. To satisfy this need, a novel magnetic recording measurement is presented that offers a direct and complete characterization of the head-medium interface. Measured data show excellent correlation with the noise power spectral density of square-wave recordings for several tape media. In addition, the measurement revealed that long wavelength components dominate the MP tape head-medium noise, resulting in a decrease of the playback broadband noise voltage power for recordings with shorter wavelength. The measurement technique provides new insight into the head-medium interface spatial characteristics.
How Sugars Pucker: Electronic Structure Calculations Map the Kinetic Landscape of Five Biologically Paramount Monosaccharides and Their Implications for Enzymatic Catalysis (2013)

Glycoside hydrolases (GHs) distort carbohydrate ring geometry along particular "catalytic itineraries" during the cleavage of glycosidic bonds, illustrating the relationship between substrate conformation and reactivity. Previous theoretical studies of thermodynamics of isolated monosaccharides offer insights into the catalytic itineraries of particular sugars. However, kinetic accessibility of carbohydrate puckering conformations and the role of exocyclic groups have not yet been thoroughly addressed. Here we present the first complete library of low-energy local minima and puckering interconversion transition states for five biologically relevant pyranose sugars: β-xylose, β-mannose, α-glucose, β-glucose, and β-N-acetylglucosamine. These were obtained by a thorough theoretical investigation each of the 38 IUPAC designated puckering geometries and all possible conformations of the exocyclic groups. These calculations demonstrate that exocyclic groups must be explicitly considered when examining these interconversion pathways. Furthermore, these data enable evaluation of previous hypotheses of why enzymes perturb ring geometries from the low-energy equatorial chair ((4)C1) conformation. They show that the relative thermodynamics alone do not universally correlate with GH catalytic itineraries. For some sugars, particular puckers offer both catalytically favorable electronic structure properties, such as anomeric carbon partial charge, and low kinetic barriers to achieve a given puckering conformation. However, different factors correlate with catalytic itineraries for other sugars; for β-N-acetylglucosamine, the key N-acetyl arm confounds the puckering landscape and appears to be the crucial factor. Overall, this study reveals a more comprehensive understanding of why particular puckering geometries are favored in carbohydrate catalysis concomitant with the complexity of glycobiology.
Expression of M2-Polarized Macrophages is Associated with Poor Prognosis for Advanced Epithelial Ovarian Cancer (2013)

Macrophages are polarized into two functionally distinct forms, M1 and M2, in response to different microenvironment. Tumor-associated macrophages (TAMs) generally have M2 phenotype and promote tumor progression. Few studies to date have described the infiltration of M2-polarized macrophages in ovarian cancer. We used two macrophages markers, CD68 and CD163, to analyze the expression of TAMs and to clarify the relationship between the M2 form and survival in advanced ovarian cancer. Clinical data of 110 patients with stages III-IV epithelial ovarian cancer at Sun Yat-sen University Cancer Center between 1999 and 2007 were retrospectively reviewed. Immunohistochemical staining of CD68 and CD163 was performed. Correlations between macrophage density and patient survival were analyzed. Our data showed that no significant difference was observed in survival between patients in the high- and the low-CD68 expression groups. In contrast, the progression-free survival (PFS) rates (p = 0.003) and overall survival (OS) rates (p = 0.004) were significantly higher in the low-CD163 expression group than in the high-CD163 expression group, respectively. Similarly, we also observed significantly improved 3-year PFS (49.8% vs. 11.0%, p < 0.001) and OS (77.4% vs. 45.0%, p < 0.001) rates in patients in the low-CD163/CD68 ratio group when compared with the high-CD163/CD68 ratio group. Multivariate analysis identified the density of CD163-positive cells as well as the ratio of CD163/CD68 as negative predictors for PFS and OS, respectively. Our results show that the infiltration of CD163-positive M2 macrophages as well as activation of macrophages towards the M2 phenotype may contribute to poor survival in advanced ovarian cancer.
Detection of Regional Mechanical Activation of the Left Ventricular Myocardium Using High Frame Rate Ultrasound Imaging (2019)

We have investigated the feasibility of noninvasive mapping of mechanical activation patterns in the left ventricular (LV) myocardium using high frame rate ultrasound imaging for the purpose of detecting conduction abnormalities. Five anesthetized, open-chest dogs with implanted combined sonomicrometry and electromyography (EMG) crystals were studied. The animals were paced from the specified locations of the heart, while crystal and ultrasound data were acquired. Isochrone maps of the mechanical activation patterns were generated from the ultrasound data using a novel signal processing method called clutter filter wave imaging (CFWI). The isochrone maps showed the same mechanical activation pattern as the sonomicrometry crystals in 90% of the cases. For electrical activation, the activation sequences from ultrasound were the same in 92% of the cases. The coefficient of determination between the activation delay measured with EMG and ultrasound was R <sup>2</sup> = 0.79 , indicating a strong correlation. These results indicate that high frame rate ultrasound imaging processed with CFWI has the potential to be a valuable tool for mechanical activation detection.
Crowdsourcing Document Relevance Assessment with Mechanical Turk (2010)

We investigate human factors involved in designing effective Human Intelligence Tasks (HITs) for Amazon’s Mechanical Turk1. In particular, we assess document relevance to search queries via MTurk in order to evaluate search engine accuracy. Our study varies four human factors and measures resulting experimental outcomes of cost, time, and accuracy of the assessments. While results are largely inconclusive, we identify important obstacles encountered, lessons learned, related work, and interesting ideas for future investigation. Experimental data is also made publicly available for further study by the community2. 1
Mutant mice derived by ICSI of evaporatively dried spermatozoa exhibit expected phenotype (2012)

Apolipoprotein E (Apoe)-deficient knockout mice were used to test the hypothesis that mutant mice preserved as evaporatively dried (ED) spermatozoa, stored at -80 °C for 6 months, and then recovered by ICSI will exhibit the same phenotype as before preservation. The birth rate of mice recovered by ICSI of evaporatively dried spermatozoa was lower than that of fresh spermatozoa (17.5 vs 38.0%). Progeny of mice preserved using evaporatively dried spermatozoa were reproductively sound. From these, the second generation of mice produced by natural mating showed lesions typical of APOE deficiency, including severe hypercholesterolemia, hypertriglyceridemia, markedly increased plasma low-density lipoprotein level, and extensive and severe atherosclerotic lesions in the aorta. We conclude that the expected phenotype caused by an induced genetic mutation can be faithfully recapitulated and sustained in subsequent generations of mice preserved and stored as ED spermatozoa and recovered using ICSI. Because it is simpler, faster, and cheaper than conventional (cryopreservation) and nonconventional (freeze-drying) preservation procedures, evaporative drying is a viable, cost-effective, and efficient method for preserving and storing valuable mutant mouse strains.
Optimized diagnosis of reflectors misalignements in radioastronomical applications (2015)

The paper presents an innovative method for the diagnosis of reflector antennas for radio astronomical applications in terms of feed misalignment. The method optimizes the number and the location of the far field sampling points exploited to retrieve the antenna status in order to reduce the time required for the measurement. The goal is achieved by introducing a relevant linear operator connecting the unknowns describing the status of the antenna and its far field pattern thanks to a proper representation of the unknowns, and by optimizing its singular values behavior. A numerical result is provided in the simple case of a phase aperture affected by tilt only, even if the approach is suited for higher order aberrations too. It show that the approach is capable to significantly reduce the number of required samples compared to a standard grid defined according to the Nyquist criterion without affecting the performance of the diagnosis.
Humoral hypercalcemia of malignancy. Release of a prostaglandin-stimulating bone-resorbing factor in vitro by human transitional-cell carcinoma cells. (1986)

Secretion by tumor cells of circulating bone-resorbing factors may frequently underlie the hypercalcemia that occurs in patients with malignancy. Efforts to identify the responsible mediators have been hampered by a lack of available human tumor cell systems suitable for study of the pathogenesis of the humoral hypercalcemia syndrome. We have established a transitional-cell carcinoma (TCC) line in vitro from a patient with humoral hypercalcemia. These cells are tumorigenic and cause hypercalcemia in athymic nude mice. Culture medium conditioned by TCC cells contains potent bone-resorbing activity in vitro, the physical and biological properties of which are similar to those of bone-resorbing activity present in the original patient's urine. The bone-resorbing activity of the TCC factor is accompanied by increased prostaglandin release from bone and is blocked by indomethacin and calcitonin. The TCC-derived bone-resorbing activity coelutes with prostaglandin-stimulating activity during gel filtration with an approximate molecular weight of 15,000. This activity is nondialyzable, stable to concentrated urea and reducing agents, and destroyed by boiling. The TCC factor does not increase cyclic AMP production in bone or kidney bioassays and does not exhibit transforming growth factor activity. We conclude that a unique macromolecular factor released by TCC cells causes bone resorption by a mechanism dependent upon stimulation of bone cell cyclooxygenase, and that this factor is the probable cause of the hypercalcemia in vivo. The TCC cell line provides a new model for study of the human humoral hypercalcemia syndrome.
Peeling off an adhesive layer with spatially varying modulus (2010)

We analyze here displacement controlled peeling of a flexible adherent off a thin layer of elastic adhesive, the elastic modulus of which does not remain uniform but varies periodically along the direction of peeling. Calculation shows that with progressive peeling, the crack front does not propagate continuously at the interface but intermittently with crack arrests and subsequent initiations. The crack gets arrested close to the location of the minimum shear modulus of the layer and initiates again only at a sufficiently large peel off load. This effect is very similar to the peeling experiment off surface patterned and microchannel embedded adhesives which results in significant enhancement of fracture toughness of the interface over smooth adhesive layers. The fracture toughness of the interface increases with the increase in thickness of the layer and the amplitude of variation in modulus. Fracture toughness is calculated to be high also for the larger value of critical stress at the opening of the crack. With the wavelength of modulus variation, it varies nonmonotonically, maximizing at an intermediate value. These results define the criterion for designing adhesive layers with spatially modulated physical properties useful for variety of applications.
Simultaneous multiple-point velocity measurements using laser-induced iodine fluorescence (1983)

A technique is demonstrated for measuring velocity at multiple locations in a plane of a gaseous flowfield using Doppler-shifted absorption with fluorescence detection from iodine molecules, excited by a sheet of tunable single-axial-mode argon-ion laser radiation at 514.5 nm. Measurements were made simultaneously at 10,000 points in an iodine-seeded supersonic flowfield with a 100 x 100 element photodiode array camera and were found to agree well with a numerical solution for the velocity field. The accuracy with which a component of velocity can be measured is limited, in the current approach, by the iodine linewidth to about +/-5 m/sec.