gebhart/patrepeval huggingface dataset:
DETERIORATION OF POLYURETHANE FILAMENTS WITH FUNGAL ENZYMES (1981)

Deterioration of polyurethane yarn was investigated with crude enzyme solution of fungi.Two types of polyurethane yarns including ether type only or ester type mainly in the part of soft structure were tested. Two fungi, Aspergillus niger FERM J-1 and Cladosporium cladosporioides FERM J-8 were employed. The test pieces of yarns were immersed in the enzyme solutions from the fungi at given pH (3.5, 4.0, or 6.5). The mixture was shaken at 30°C for two weeks. The incubated yarns were observed by scanning electron micrography and some physical properties of the yarns were examined. Furthermore, the chemical changes of the yarns and the liberations of carboxyl group and ammonia were measured.The tensile strength, viscoelasticity and extension behavior were remarkably changed. On the enzymatic digestion, various types of degradation were caused by the hydrolysis of several different type bonds in these polymers. Protease and esterase activities were in Asp. niger and Clad. cladosporioides. Urease was only detected in Asp. niger. These enzymes were inducible enzymes. Hydrolysis took place with enzymes of endo type.
The trastuzumab era: current and upcoming targeted HER2+ breast cancer therapies. (2020)

Human Epidermal Growth Factor Receptor 2-positive breast cancer (HER2+ BC) is defined by increased amplification of the ERBB2/neu oncogene and/or overexpression of its associated HER2 transmembrane receptor protein. HER2+ BC represents approximately 15-20% of breast cancer, and it is independently associated with a higher grade, more aggressive phenotype, and worse prognosis. With the advent of trastuzumab, the prognostic landscape for HER2+ BC patients has considerably improved. However, both de novo and acquired resistance to trastuzumab remain a significant obstacle for many patients, requiring novel therapies for further clinical benefit. Over the last two decades, there has been extraordinary progress in the development of HER2+ BC treatment regimens, with extensions into HER2-amplified gastroesophageal junction cancer via the NCI-MATCH precision medicine trial program (NCT02465060). Trastuzumab, pertuzumab, T-DM1, and lapatinib are commonly recommended as a single agent (along with chemotherapy) or in combinations of anti-HER2 agents in neoadjuvant, adjuvant and metastatic settings according to National Comprehensive Cancer Network (NCCN) guidelines. Currently, the combination of trastuzumab, pertuzumab, and taxane chemotherapy are first-line for HER2+/HR- metastatic breast cancer with potential breakthrough therapies such as trastuzumab-deruxtecan (DS-8201a), margetuximab and tucatinib (ONT-380) on the horizon. Furthermore, recent clinical trials have demonstrated the potential utility of hormone receptor status, PAM-50 luminal intrinsic subtype, PD-L1, and TIL as predictive biomarkers for response to HER2+ therapies. We briefly introduce the origin of HER2, the invention of trastuzumab, and the classification of HER2+ BC. Each HER2-targeted therapy is then presented by indication, mechanism of action, and relevant clinical trials with subsequent elaboration and contextualization within clinical settings with an epilogue of potential future biomarkers for clinical use in HER2+ BC. We summarize the most significant and updated research in clinical practice relevant to HER2+ BC management and highlight the clinical status of upcoming anti-HER2 agents as well as immunotherapy drugs in combination with anti-HER2 agents.
Thyroid hormone and thyroid hormone analogues in the treatment of heart failure (1999)

The thyroid hormone analogue DITPA is a promising potential new treatment for heart failure. Although the mechanism of action is incompletely determined, it is clear that DITPA improves systolic as well as diastolic function. It is also clear that the effects of DITPA are intrinsic to the muscle and not the result of changes in the structure or geometry of the left ventricle. On the basis of these experimental studies, we applied to the USA Food and Drug Administration for an Investigational New Drug application to study the use of DITPA in patients. These studies are currently in progress. While we await the outcome of these clinical trials, it is important to emphasize that even if the end-point is not a new drug to treat heart failure, our investigations are based on a systematic evaluation integrating biochemistry and physiology. We believe that this is the way to approach the problem of developmental pharmacology.
Characterization and monitoring of variable NA and variable coherence capable photosteppers utilizing the phase shift focus monitor reticle (1995)

The phase shift focus monitor is a relatively new technique which can be used to determine the optimal imaging plane for a photo-stepper. This determination ofbest focus is accomplished through phase shifting technology developed and patented by IBM. Adapting this concept to an overlay measurement target has advantages of simultaneous x and y measurements, high precision, and automated data collection. Printed on the reticle are phase shifting structures using the box-in-box pattern. These phase shifting structures produce lateral shifting ofimages at the wafer plane when they are imaged out offocus. This is a direct result from utilizing non- 1 80 degree phase shifting material. When the patterns are imaged in focus, no lateral shifting, or overlay error is exhibited by the box-in-box patterns. It has been found that the overlay error of the printed structures increases with the magnitude of defocus. If overlay data is collected from several different levels of defocus, a direct linear function can be found to relate best focus to the overlay error of the printed box-in-box patterns. Additionally, it can be shown that this relation is dependent upon the NA (numerical aperture) and PC (partial coherence) of the imaging system. This technique can be used as a very powerful analysis tool for characterizing photo-steppers, as it provides for the collection ofvast amounts ofdata about a stepper's condition rather quickly. It is laid out in an arrayed pattern with 121 modules in an 1 1 x 11 matrix. The complete matrix is contained in a 22 x 22 mm field (at wafer level on a 5x reduction stepper).Each module contains the phase-shifted box-in box patterns. Several potential applications have been suggested already. One wafer can be used to collect data on current best focus and field tilts in a few minutes. More static characteristics specific to the lens can be determined as well, i.e. astigmatism and field curvature. All of this information can be collected by measuring the overlay error from several of the 121 module positions in the field. This paper will discuss techniques to use the focus monitor to characterize steppers equipped with variable NA and PC. In addition, it can be shown that the monitor can provide quick and accurate measurements to verify and track the stepper's own internal diagnostics for statistical process control. Keywords: phase shift, focus, photostepper, reticle, numerical aperture, coherence, overlay
Decreased Proteolytic Activity of the Mitochondrial Amyloid-β Degrading Enzyme, PreP Peptidasome, in Alzheimer's Disease Brain Mitochondria (2011)

Accumulation of amyloid-β peptide (Aβ), the neurotoxic peptide implicated in the pathogenesis of Alzheimer's disease (AD), has been shown in brain mitochondria of AD patients and of AD transgenic mouse models. The presence of Aβ in mitochondria leads to free radical generation and neuronal stress. Recently, we identified the presequence protease, PreP, localized in the mitochondrial matrix in mammalian mitochondria as the novel mitochondrial Aβ-degrading enzyme. In the present study, we examined PreP activity in the mitochondrial matrix of the human brain's temporal lobe, an area of the brain highly susceptible to Aβ accumulation and reactive oxygen species (ROS) production. We found significantly lower hPreP activity in AD brains compared with non-AD age-matched controls. By contrast, in the cerebellum, a brain region typically spared from Aβ accumulation, there was no significant difference in hPreP activity when comparing AD samples to non-AD controls. We also found significantly reduced PreP activity in the mitochondrial matrix of AD transgenic mouse brains (Tg mAβPP and Tg mAβPP/ABAD) when compared to non-transgenic aged-matched mice. Furthermore, mitochondrial fractions isolated from AD brains and Tg mAβPP mice had higher levels of 4-hydroxynonenal, an oxidative product, as compared with those from non-AD and nonTg mice. Accordingly, activity of cytochrome c oxidase was significantly reduced in the AD mitochondria. These findings suggest that decreased PreP proteolytic activity, possibly due to enhanced ROS production, contributes to Aβ accumulation in mitochondria leading to the mitochondrial toxicity and neuronal death that is exacerbated in AD. Clearance of mitochondrial Aβ by PreP may thus be of importance in the pathology of AD.
Brute-Force Hyperpolarization for NMR and MRI (2015)

Hyperpolarization (HP) of nuclear spins is critical for ultrasensitive nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). We demonstrate an approach for >1500-fold enhancement of key small-molecule metabolites: 1-(13)C-pyruvic acid, 1-(13)C-sodium lactate, and 1-(13)C-acetic acid. The (13)C solution NMR signal of pyruvic acid was enhanced 1600-fold at B = 1 T and 40 °C by pre-polarizing at 14 T and ∼2.3 K. This "brute-force" approach uses only field and temperature to generate HP. The noted 1 T observation field is appropriate for benchtop NMR and near the typical 1.5 T of MRI, whereas high-field observation scales enhancement as 1/B. Our brute-force process ejects the frozen, solid sample from the low-T, high-B polarizer, passing it through low field (B < 100 G) to facilitate "thermal mixing". That equilibrates (1)H and (13)C in hundreds of milliseconds, providing (13)C HP from (1)H Boltzmann polarization attained at high B/T. The ejected sample arrives at a room-temperature, permanent magnet array, where rapid dissolution with 40 °C water yields HP solute. Transfer to a 1 T NMR system yields (13)C signals with enhancements at 80% of ideal for noted polarizing conditions. High-resolution NMR of the same product at 9.4 T had consistent enhancement plus resolution of (13)C shifts and J-couplings for pyruvic acid and its hydrate. Comparable HP was achieved with frozen aqueous lactate, plus notable enhancement of acetic acid, demonstrating broader applicability for small-molecule NMR and metabolic MRI. Brute-force avoids co-solvated free-radicals and microwaves that are essential to competing methods. Here, unadulterated samples obviate concerns about downstream purity and also exhibit slow solid-state spin relaxation, favorable for transporting HP samples.
Post‐thaw Survival and Longevity of Bull Spermatozoa Frozen with an Egg Yolk‐based or Two Egg Yolk‐free Extenders after an Equilibration Period of 18 h (2007)

The aim of the present study was to determine the suitability of using two egg yolk-free commercial extenders, Andromed and Biociphos Plus as compared with the Tris-egg yolk based diluent Biladyl, for the cryopreservation of bull spermatozoa when the freezing protocol involved holding the extended semen at 4 degrees C for 18 h before the freezing. Six ejaculates from each of 10 Holstein bulls were collected by using artificial vagina. The ejaculates were evaluated for volume, sperm concentration and motility, divided in to three equal volumes, and diluted, respectively, with the three extenders as specified above. Extended semen was equilibrated for 18 h at 4 degrees C and frozen in 0.25-ml straws. After thawing, 100-mul aliquots of semen were labelled with SYBR-14, PI and PE-PNA (Phycoerythrin-conjugated Peanut agglutinin) and analysed by flow cytometry at 0, 3, 6 and 9 h after incubation at 37 degrees C. A General Lineal Model procedure for repeated measures was used to determine the effects of extender, bull, replicate and the interaction between them, on sperm viability and acrosomal integrity. Semen samples frozen with Biladyl showed higher (p < 0.001) sperm survival after 0 h (47.9%) and 9 h (30.3%) of incubation than those frozen with Andromed (38.5% and 17.3%, after 0 and 9 h respectively) or Biociphos Plus (34.9% and 21.6%, after 0 and 9 h respectively). The bull and replicate had significant effects (p < 0.001) on both sperm viability and acrosomal integrity, but the interactions between bull and extender and between replicate and extender were not significant. It was concluded that, when holding the semen overnight before freezing, the use of Biladyl results in higher sperm survival and longevity than the use of Andromed or Biociphos Plus.
U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non–Small Cell Lung Cancer (2017)

On October 18, 2016, the FDA approved atezolizumab (TECENTRIQ; Genentech, Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months [95% confidence interval (CI), 11.8-15.7] in the atezolizumab arm compared with 9.6 months (95% CI, 8.6-11.2) in the docetaxel arm [hazard ratio (HR) = 0.74; 95% CI, 0.63-0.87; <i>P</i> = 0.0004]. Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI, 9.7-16.0) and 9.7 months (95% CI, 8.6-12.0; HR = 0.69; 95% CI, 0.52-0.92) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (≥20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (≥2%) grade 3 to 4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, aspartate aminotransferase increase, alanine aminotransferase increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of grade 3 to 4 pneumonitis, hepatitis, colitis, and thyroid disease. <i>Clin Cancer Res; 23(16); 4534-9. ©2017 AACR</i>.
Numerical solution of fractional differential equations via a Volterra integral equation approach (2013)

Abstract The main focus of this paper is to present a numerical method for the solution of fractional differential equations. In this method, the properties of the Caputo derivative are used to reduce the given fractional differential equation into a Volterra integral equation. The entire domain is divided into several small domains, and by collocating the integral equation at two adjacent points a system of two algebraic equations in two unknowns is obtained. The method is applied to solve linear and nonlinear fractional differential equations. Also the error analysis is presented. Some examples are given and the numerical simulations are also provided to illustrate the effectiveness of the new method.
Assisted Point Mapping to Enable Cost-effective Deployment of Intelligent Building Applications (2016)

Over the past years intelligent building applications that promise to dramatically reduce energy consumption, improve occupant comfort and streamline maintenance have been proposed. However their adoption has met a step barrier in the unexpectedly high cost in mapping data from building automation systems into these applicationsâ€™ data models. In fact the industry does not have a common convention on how to name points. Generally, names are correlated with the semantic of the variables they represent, but typically engineers have the freedom to set up variable names according to their preferences. In order to meet market requirements, an â€œidealâ€ algorithm would have four properties: 1) high accuracy and especially low false positive rate (i.e. small number of erroneously mapped points); 2) ability to infer complex relationships between data points (e.g. grouping points by equipment, classifying equipment, establishing relationship between equipment); 3) easy to use: it should leverage only readily available knowledge and data about the system (i.e. not requiring the installation of additional sensors); 4) minimizing the need of having a domain expert using it. In the last few years the research community has devoted increasing attention in automating the process of mapping data points from existing BAS.Â However, none of the published work meets the market requirements.Â Most require an expert user, some are not â€œeasy to useâ€ and none can automatically infer complex relationships. This paper presents a novel algorithm and its software implementation to tackle the mapping problem. This work contributes moving the state-of-the-art a bit furtherÂ in the sense that this algorithm can be applied to various dataset with minor or no modification (i.e. no expert in the loop), it is the first to automatically infer complex relationships and it only ingests point names as input (i.e. easiness of use). The algorithm has been tested against the largest and most diversified dataset in the literature comprising 25299 points, 7 buildings, 4 vendors and 3 distributors. Preliminary results suggest that it is able to correctly map about 92% of the point required by a test application and to successfully identify about 92% of VAVs, 100% of AHU and FCU.
Multiple roles for Sox2 in the developing and adult mouse trachea (2009)

The esophagus, trachea and lung develop from the embryonic foregut, yet acquire and maintain distinct tissue phenotypes. Previously, we demonstrated that the transcription factor Sox2 is necessary for foregut morphogenesis and esophagus development. We show that Sox2 is also required for the normal development of the trachea and lung. In both the embryo and adult, Sox2 is exclusively expressed in the epithelium of the trachea and airways. We use an Nkx2.5-Cre transgene and a Sox2 floxed allele to conditionally delete Sox2 in the ventral epithelial domain of the early anterior foregut, which gives rise to the future trachea and lung buds. All conditional mutants die of respiratory distress at birth, probably due to abnormal differentiation of the laryngeal and tracheal cartilage as a result of defective epithelial-mesenchymal interaction. About 60% of the mutants have a short trachea, suggesting that the primary budding site of the lung shifts anteriorly. In the tracheal epithelium of all conditional mutants there are significantly more mucus-producing cells compared with wild type, and fewer basal stem cells, ciliated and Clara cells. Differentiation of the epithelium lining the conducting airways in the lung is abnormal, suggesting that Sox2 also plays a role in the differentiation of embryonic airway progenitors into specific lineages. Conditional deletion of Sox2 was then used to test its role in adult epithelium maintenance. We found that epithelial cells, including basal stem cells, lacking Sox2 show a reduced capacity to proliferate in culture and to repair after injury in vivo. Taken together, these results define multiple roles for Sox2 in the developing and adult trachea.
The acidic activation domains of the baculovirus transactivators IE1 and IE0 are functional for transcriptional activation in both insect and mammalian cells (2004)

The acidic activation domains (AADs) of the baculovirus transactivators IE1 and IE0 are essential for transcriptional transactivation. To compare the relative transcriptional activation potentials of IE1 and IE0 AADs of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Orgyia pseudotsugata MNPV (OpMNPV), we constructed two ecdysone receptor (EcR)-based inducible expression systems to analyse six baculovirus AADs in two insect cell lines (Ld652Y and Sf9) and two mammalian cell lines (NIH-3T3 and CHO). For insect cell expression, the AADs were fused to the C, D, E and F domains of the spruce budworm Choristoneura fumiferana EcR. For mammalian cell expression the AADs were fused to the E and F domains of mammalian Mus musculus retinoid X receptor. In Ld652Y and Sf9 cells, chimeric proteins containing the AcMNPV AADs activated gene expression to higher levels than those containing the OpMNPV AADs. In NIH-3T3 cells, chimeras containing AcMNPV IE1 and IE0 AADs consistently activated gene expression to higher levels than the archetypal mammalian herpesvirus VP16 AAD. In contrast, OpMNPV AADs only activated expression by 5-15 % relative to the VP16 AAD. In CHO cells, both AcMNPV and OpMNPV AADs exhibited intermediate transactivation levels relative to VP16 AAD. These results show that the baculovirus AADs are functional for transcriptional activation in mammalian cells and that AcMNPV AADs generally appear to be more potent than OpMNPV AADs in both insect and mammalian cells.
[Clinical examination of serum bile acids for the diagnosis of hepatobiliary diseases]. (1989)

There are four major clinical methods for determination of serum total bile acids (TBA) levels. The first is fasting TBA (FTBA), which increases specifically in liver disorders. It increased more sensitively and normalized faster than transaminases in acute hepatic injury. Secondly, the bile acid loading test is useful to examine the degree of liver cell damage. This test improved the detection rate of FTBA for the liver dysfunction and reflects the severity of the diseases. The third is the profiles and dynamic changes of individual bile acids (IBA). In liver cirrhosis synthesis of cholic acid (CA) was lowered and the ratio of CA + deoxycholic acid (DCA)/chenodeoxycholic acid (CDCA) + lithocholic acid (LCA) was less than 1. On the other hand in cholestasis, secondary bile acids were reduced and CA increased markedly due to the regulation of bile acid metabolism, so that the ratio of CA + DCA/CDCA + LCA was more than 1. This phenomenon can be used for the differential diagnosis of liver cell damage and cholestasis. The last is the detection of unusual bile acids, such as 3 beta-hydroxy-5-cholenoic acid is useful for the marker of hepatic cell carcinoma and the screening of congenital biliary atresia.
Automated Immunomagnetic Processing and Separation of <i>Legionella Pneumophila</i> with Manual Detection by Sandwich ELISA and PCR Amplification of the ompS Gene (2010)

The culture-independent and automated detection of bacteria in the environment is a scientific and technological challenge. For detection alone, a number of sensitive methods are known (e.g., PCR, enzyme-linked immunosorbent assay [ELISA], fluorescent in situ hybridization) but a major problem remaining is the enrichment and separation of the bacteria that usually occur at low concentrations. Here, we present an automated capturing and separation system, which can easily be combined with one of the sensitive detection techniques. We have developed a method for enrichment and detection of Legionella pneumophila in liquid media. Concentrated microorganisms were either detected by PCR or by sandwich ELISA. The limit of detection with the immunological assay was about 750 bacteria. Using PCR, the equivalent of about 2000 genomes could be detected. The assays were then transferred to a laboratory prototype for automated processing. It was possible to automatically enrich L. pneumophila by immunomagnetic separation (IMS), and again, the bacteria were detected by sandwich ELISA and PCR amplification of the ompS gene. As a novel aspect, ompS gene was used for the first time as a target for the detection of L. pneumophila on magnetic beads. The aim of this work was to develop an automated procedure and a device for IMS of bacteria. With Legionella as a model organism, we could show that such a novel fully automated system can be an alternative to time-consuming conventional cultivation methods for detecting bacteria or other microorganisms.