gebhart/patrepeval huggingface dataset:
Development of Tau Aggregation Inhibitors for Alzheimer's Disease (2009)

A variety of human diseases are suspected to be directly linked to protein misfolding. Highly organized protein aggregates, called amyloid fibrils, and aggregation intermediates are observed; these are considered to be mediators of cellular toxicity and thus attract a great deal of attention from investigators. Neurodegenerative pathologies such as Alzheimer's disease account for a major part of these protein misfolding diseases. The last decade has witnessed a renaissance of interest in inhibitors of tau aggregation as potential disease-modifying drugs for Alzheimer's disease and other "tauopathies". The recent report of a phase II clinical trial with the tau aggregation inhibitor MTC could hold promise for the validation of the concept. This Review summarizes the available data concerning small-molecule inhibitors of tau aggregation from a medicinal chemistry point of view.
Compact microlenslet-array-based magnifier (2004)

An ultracompact optical imaging system allowing various magnifications or demagnifications and based on microlenslet arrays is presented for the first time to our knowledge. This research generalizes recent findings regarding microlenslet-array-based 1:1 relay systems [Appl. Opt. 42, 6838 (2003)]. Through optical ray tracing, the feasibility of magnifying gray-scale images through a stack of two dissimilar microlenslet arrays is demonstrated for the first time to our knowledge. Results presented specifically demonstrate that a compact imaging system operating at a magnification of 2 is feasible with an overall length of approximately 9 mm. Optical aberrations of the most basic configuration are evaluated, and optimization is discussed.
PLR: A Software Approach to Transient Fault Tolerance for Multicore Architectures (2008)

Transient faults are emerging as a critical concern in the reliability of general-purpose microprocessors. As architectural trends point toward multicore designs, there is substantial interest in adapting such parallel hardware resources for transient fault tolerance. This paper presents process-level redundancy (PLR), a software technique for transient fault tolerance, which leverages multiple cores for low overhead. PLR creates a set of redundant processes per application process and systematically compares the processes to guarantee correct execution. Redundancy at the process level allows the operating system to freely schedule the processes across all available hardware resources. PLR uses a software-centric approach to transient fault tolerance, which shifts the focus from ensuring correct hardware execution to ensuring correct software execution. As a result, many benign faults that do not propagate to affect program correctness can be safely ignored. A real prototype is presented that is designed to be transparent to the application and can run on general-purpose single-threaded programs without modifications to the program, operating system, or underlying hardware. The system is evaluated for fault coverage and performance on a four-way SMP machine and provides improved performance over existing software transient fault tolerance techniques with a 16.9 percent overhead for fault detection on a set of optimized SPEC2000 binaries.
Isoxazolinyl derivatives of anthranilic acid as antiinflammatory agents (2003)

A number of 5-substituted-N-[4'-(substitutedphenyl)aminomethyl-5'-(substitutedphenyl)isoxazolin-2'-yl]anthranilic acids have been synthesized by the Mannich reaction of 5-substituted-N-[5'-(substitutedphenyl)isoxazolin-2'-yl]anthranilic acids, which in turn is synthesized by the reaction of 5-substituted-N-chalconylanthranilic acids. In this series, compounds 9, 11, 15 and 18 show significant protection against carrageenan induced rat's paw oedema with lower ulcerogenic liability than phenylbutazone. The most active compound of this series is N-[5'-(m-methoxy, p-hydroxyphenyl)isoxazolin-2'-yl]anthranilic acid which has shown higher antiinflammatory activity and lower ulcerogenic property than phenylbutazone.
An Image-Based Model of the Whole Human Heart with Detailed Anatomical Structure and Fiber Orientation (2012)

Many heart anatomy models have been developed to study the electrophysiological properties of the human heart. However, none of them includes the geometry of the whole human heart. In this study, an anatomically detailed mathematical model of the human heart was firstly reconstructed from the computed tomography images. In the reconstructed model, the atria consisted of atrial muscles, sinoatrial node, crista terminalis, pectinate muscles, Bachmann's bundle, intercaval bundles, and limbus of the fossa ovalis. The atrioventricular junction included the atrioventricular node and atrioventricular ring, and the ventricles had ventricular muscles, His bundle, bundle branches, and Purkinje network. The epicardial and endocardial myofiber orientations of the ventricles and one layer of atrial myofiber orientation were then measured. They were calculated using linear interpolation technique and minimum distance algorithm, respectively. To the best of our knowledge, this is the first anatomically-detailed human heart model with corresponding experimentally measured fibers orientation. In addition, the whole heart excitation propagation was simulated using a monodomain model. The simulated normal activation sequence agreed well with the published experimental findings.
Inducible nitric oxide synthase expression in coronary arteries of transplanted human hearts with accelerated graft arteriosclerosis. (1997)

Inducible nitric oxide synthase (iNOS) is a high-output isoform of NOS that produces nitric oxide (NO), a nonspecific immune effector molecule. In some animal models of autoimmunity, the induction of iNOS has been shown to lead to inflammation and tissue damage, and it has been suggested that iNOS is an immune mediator in humans as well. Using in situ hybridization and immunohistochemical techniques, we demonstrate that iNOS mRNA and protein are present in the coronary arteries of transplanted human hearts with accelerated graft arteriosclerosis (AGA). iNOS is expressed in cells morphologically consistent with macrophages in the neointima of 7 of 10 of the transplanted vessels with AGA that were examined. In serial sections, these same cells express the macrophage marker CD68. In contrast, iNOS is absent from five native coronary arteries with atherosclerosis and absent from two normal coronary arteries. Although iNOS is expressed in macrophages in AGA, its role in the pathogenesis of AGA is unknown.
Improved Training with Curriculum GANs (2018)

In this paper we introduce Curriculum GANs, a curriculum learning strategy for training Generative Adversarial Networks that increases the strength of the discriminator over the course of training, thereby making the learning task progressively more difficult for the generator. We demonstrate that this strategy is key to obtaining state-of-the-art results in image generation. We also show evidence that this strategy may be broadly applicable to improving GAN training in other data modalities.
Quantitative measurement of sn-1,2-diacylglycerols present in platelets, hepatocytes, and ras- and sis-transformed normal rat kidney cells. (1986)

A simple enzymatic method for the quantitation of the mass of sn-1,2-diacylglycerol (DAG) present in crude lipid extracts was developed to assess the function of DAGs as intracellular "second messengers" of extracellular agents and of oncogene products. The assay employed Escherichia coli DAG kinase which constituted approximately 15% of the membrane protein of a plasmid-bearing strain and defined mixed micellar conditions to solubilize the DAG present and allow its quantitative conversion to [32P]phosphatidic acid. The assay was proportional with the amount of DAG added over the range of 25 pmol to 25 nmol. The rapid rise of DAG in platelets stimulated with thrombin (210% over basal) and in hepatocytes stimulated with vasopressin (230% over basal) was quantitated and the values agreed with previous measurements. The amounts of DAG in normal rat kidney (NRK) cells grown at 34 and 38 degrees C, respectively, were 0.47 and 0.61 nmol/100 nmol of phospholipid. In K-ras-transformed NRK cells grown at 34 or 38 degrees C, DAG levels were elevated 168 or 138%, respectively. When a temperature-sensitive K-ras NRK cell line was investigated, the amount of DAG present was elevated at the permissive but not at the restrictive temperature. These data are consistent with the K-ras protein functioning in transmembrane signalling by activating phospholipase C. Protein kinase C (Ca2+/phospholipid-dependent enzyme) activation by DAG may play an important role in cellular transformation.
Enhancement of Vitamin E Levels in Corn (2002)

Vitamin E is the common name that describes eight naturally occurring compounds possessing alpha-tocopherol activity. These eight vitamin E compounds are collectively termed tocols, and all have antioxidant activity. There is natural variation among different corn breeding lines for levels of tocols. The two predominant isomers present in corn grain are gamma-tocopherol and alpha-tocopherol. Alpha-tocopherol is considered more desirable for human and animal consumption because it has higher biological activity than gamma-tocopherol. Most corn breeding lines naturally have much more gamma-tocopherol than alpha-tocopherol. Therefore a breeding goal is to increase levels of alpha-tocopherol relative to gamma-tocopherol. However, recent research suggests that gamma-tocopherol and compounds metabolized from it have properties important to human health that are unique from properties of alpha-tocopherol. Therefore it may be desirable to not only increase levels of alpha-tocopherol in corn grain, but also levels of gamma-tocopherol. Determination of levels of tocopherols in corn grain is very laborious, requires HPLC analysis and is too time consuming for use in routine commercial corn breeding programs. Therefore we are performing biotechnology enabled molecular marker mapping of chromosomal regions with genes that control levels and ratios of alpha- and gamma-tocopherol. Breeders can use molecular markers we have identified to expediently select for desirable alleles of genes that will improve levels of alpha- and gamma-tocopherol in corn grain, without having to perform laborious HPLC assays. Another biotechnology strategy we have initiated is genetic transformation of corn with the gamma-tocopherol methyl transferase gene to enhance conversion of gamma-tocopherol to alpha-tocopherol and thus increase levels of alpha-tocopherol. This transgenic strategy has been demonstrated in the model plant Arabidopsis, and we are now applying this approach to corn.
Behavioral Implications of Prenatal and Early Postnatal Exposure to Chemical Pollutants (1974)

Although this Conference focuses on the fetus and child, it should not deflect us from the larger issue-effects over the total lifespan. Early developmental stages are important less in themselves than in what they portend. So that you do not conclude, to our immense embarrassment, that we are about to envelop you in a Freudian mist, let us immediately brace these statements with some quantitative perspectives. Assume that exposure to an environmental contaminant takes place over a lifetime-a contaminant that, like methylmercury, can destroy brain tissue (although we don't know whether a threshold for damage exists for methylmercury). What are the implications for central nervous system function and performance? Figure 1 represents extrapolations from a function postulated by Kety,1 on the basis of the then existing literature, to represent aging of the brain. It shows a decline in neuronal cell density (paralleled by declines in oxygen consumption and blood circulation) of about 20% to 25% between age 25 and 75. There is substantial evidence that the central nervous system undergoes a continuous loss of cells throughout postnatal life, that a large proportion of cells die during morphogenesis, and that numerous structural and chemical changes take place both in the developing and the aging brain. An important, in fact a key, concurrent process is the decline with advancing age in a wide range of behavioral performance measures. Weiss and Simon2 calculated the additional decrease that would be imposed by enhancing the rate of loss calculated by Kety. Even as minute an increment as 0.1% represents a significant acceleration in terms of equivalent brain age.
Activation of mTOR Ameliorates Fragile X Premutation rCGG Repeat-Mediated Neurodegeneration (2013)

Fragile X associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder caused by aberrant expansion of CGG repeats in 5' UTR of FMR1 gene. The elevated mRNA confers a toxic gain-of-function thought to be the critical event of pathogenesis. Expressing rCGG90 repeats of the human FMR1 5'UTR in Drosophila is sufficient to induce neurodegeneration. Rapamycin has been demonstrated to attenuate neurotoxicity by inducing autophagy in various animal models of neurodegenerative diseases. Surprisingly, we observed rapamycin exacerbated rCGG90-induced neurodegenerative phenotypes through an autophagy-independent mechanism. CGG90 expression levels of FXTAS flies exposed to rapamycin presented no significant differences. We further demonstrated that activation of the mammalian target of rapamycin (mTOR) signaling could suppress neurodegeneration of FXTAS. These findings indicate that rapamycin will exacerbate neurodegeneration, and that enhancing autophagy is insufficient to alleviate neurotoxicity in FXTAS. Moreover, these results suggest mTOR and its downstream molecules as new therapeutic targets for FXTAS by showing significant protection against neurodegeneration.
0.3-micron optical lithography using a phase-shifting mask (1989)

Improved resolution of an available i-line (365nm) stepper using a phase-shifting mask is discussed. The resolution investigated here is not only for periodic lines but also for isolated spaces and hole patterns. To obtain a narrow bright line for printing a fine isolated space on a wafer, two additional line apertures with widths smaller than the critical dimension of the stepper lens are placed on each side of the main aperture of the mask. The optical phase of the main aperture and those of additional apertures are opposite. The additional apertures play a role in reducing the bright feature size to less than the line spread function of the lens. Similarly, printing a fine hole is accomplished by using a main aperture surrounded by four additional apertures. The intensity distribution on the wafer is calculated by comparing the results obtained with a phase-shifting mask and those obtained with a conventional transmission mask. Patterns are also printed on the wafer using an i-line stepper with a nominal 0.55 μm resolution. A pattern of 0.3-μm lines and spaces, 0.3-μm isolated spaces and 0.4-μm hole patterns are resolved using the phase-shifting mask. This resolution is impossible with a conventional transmission mask. The effects of variations in the optical phase of the additional apertures are also investigated. The intensity calculations and experimental results suggest that it is possible to control the position of the best focal plane by changing the optical phases of the additional apertures.
Monitoring of partially broken rotor bars in induction machine drives (2010)

Detection of rotor bar asymmetries in induction machines operated by an inverter can be difficult due to disturbances introduced by the fast switching power devices. Furthermore interference of the fault indicator with control dynamics of the load level lower the accuracy of most detection methods proposed. These disturbances can be avoided if the detection can be realized at standstill of the drive using the inverter as a measurement device. In this paper the sensitivity of a method is analyzed that enables the detection of rotor bar defects at zero load and around standstill. The method is based on the excitation of the machine with voltage pulses generated by the switching of the inverter. Measuring the resulting response of the machine phase currents, the spatial distribution of the transient inductance can be identified with high accuracy. An asymmetry in the rotor bars leads to a distinct change in the spatial distribution of the transient flux linkage and thus also of the transient inductance. The accuracy is such that even partial broken bars can be detected. Measurements on a machine with a specially manufactured copper rotor cage are presented. The resistance of a single bar is stepwise increased by changing the material of the bar from copper to aluminum, brass, and finally steel. It is shown that even the stepwise increase of a single bar resistance before the bar is broken can be clearly detected. It is thus possible to monitor the machine even for a developing rotor defect.
In Situ Sensor Technology for Simultaneous Spectrophotometric Measurements of Seawater Total Dissolved Inorganic Carbon and pH (2015)

A new, in situ sensing system, Channelized Optical System (CHANOS), was recently developed to make high-resolution, simultaneous measurements of total dissolved inorganic carbon (DIC) and pH in seawater. Measurements made by this single, compact sensor can fully characterize the marine carbonate system. The system has a modular design to accommodate two independent, but similar measurement channels for DIC and pH. Both are based on spectrophotometric detection of hydrogen ion concentrations. The pH channel uses a flow-through, sample-indicator mixing design to achieve near instantaneous measurements. The DIC channel adapts a recently developed spectrophotometric method to achieve flow-through CO2 equilibration between an acidified sample and an indicator solution with a response time of only ∼ 90 s. During laboratory and in situ testing, CHANOS achieved a precision of ±0.0010 and ± 2.5 μmol kg(-1) for pH and DIC, respectively. In situ comparison tests indicated that the accuracies of the pH and DIC channels over a three-week time-series deployment were ± 0.0024 and ± 4.1 μmol kg(-1), respectively. This study demonstrates that CHANOS can make in situ, climatology-quality measurements by measuring two desirable CO2 parameters, and is capable of resolving the CO2 system in dynamic marine environments.
Inward rectifier K+ channel Kir2.3 (IRK3) in reactive astrocytes from adult rat brain (2000)

Astrocytic inward rectifying K(+) channels that participate in K(+) spatial buffering in the central nervous system have been extensively investigated, but specific gene products have not been fully identified. We studied primary cultured reactive astrocytes of stellate and polygonal morphology from adult rat brains, as well as stellate astrocytes from neonatal rat brains. Single-channel recordings of cell-attached patches revealed that polygonal reactive astrocytes expressed only one hyperpolarization-activated single-channel conductance of 11-15 pS whose open probability was independent of voltage, whereas stellate reactive and stellate neonatal astrocytes exhibited two conductances, 11-15 pS and 24-27 pS. All three subtypes of astrocytes exhibited a hyperpolarization-activated macroscopic inward K(+) current that was strongly rectifying and was abrogated by 1 mM intracellular Mg(2+) introduced during conventional but not perforated patch whole-cell recording. This Mg(2+)-sensitive current comprised the total inward rectifier current in polygonal reactive astrocytes, but only a fraction of the inward rectifier current in stellate reactive and stellate neonatal astrocytes. Because a strongly rectifying, inward rectifier K(+) channel with a single-channel conductance of 11-15 pS that is voltage independent is consistent with features of Kir2.3 (IRK3), we performed immunofluorescence experiments with anti-Kir2.3 and anti-glial fibrillary acidic protein antibodies. Both antibodies co-localized to all three subtypes of astrocytes in primary culture and to reactive astrocytes in situ within brain and gelatin sponge implants. Our data indicate that astrocytes of both polygonal and stellate morphology, from both adult and neonatal rat brain, express Kir2.3 both in vivo and in vitro. Constitutive expression of Kir2.3 regardless of cell morphology or age of origin of the source tissue suggests an important functional role for this channel in astrocytes.
Cyclin D1 and prognosis in human breast cancer (1996)

We have used immunohistochemical staining to assess the expression of cyclin D1 in formalin-fixed sections of 345 breast carcinomas, dating back 20 years. Clinical follow-up data were available on all patients. Approximately 50% of the tumours showed excessive nuclear staining for cyclin D1 as compared with normal epithelium. Some tumours showed strong cytoplasmic staining in the absence of nuclear staining, and around 25% of the tumours were judged to be negative for nuclear cyclin D1. Contrary to expectations, moderate/strong staining for cyclin D1 was associated with improved relapse-free and overall survival relative to patients whose tumours stained weakly or negatively. Conversely, tumours that were considered negative for cyclin D1 staining had an adverse prognosis, and the poor outcome was further accentuated if the tumours were also oestrogen receptor-negative. A possible explanation for our findings is that tumours in which cyclin D1 levels are abnormally low may have sustained mutations in other genes, such as RBI and that it is this abnormality that has the more significant impact on survival from breast cancer.
Molecular cloning, genomic characterization and expression of novel human α1A‐adrenoceptor isoforms (1998)

We have isolated and characterized from human prostate novel splice variants of the human alpha1A-adrenoceptor, several of which generate truncated products and one isoform, alpha(1A-4), which has the identical splice site as the three previously described isoforms. Long-PCR on human genomic DNA showed that the alpha(1A-4) exon is located between those encoding the alpha(1A-1) and alpha(1A-3) variants. CHO-K1 cells stably expressing alpha(1A-4) showed ligand binding properties similar to those of the other functional isoforms as well as agonist-stimulated inositol phosphate accumulation. Quantitative PCR analyses revealed that alpha(1A-4) is the most abundant isoform expressed in the prostate with high levels also detected in liver and heart.
Antixenosis-A New Term Proposed to Define Painter's "Nonpreference" Modality of Resistance (1978)

Much of the wide acceptance and popularity of Reginald Painter's classification of the mechanisms of plant resistance to insect pests stems not only from its simplicity and apparent generality, but also because it accurately describes insect and plant responses. Based on some of his own previous work (Painter 1936, 1941), Painter in his classical book “Insect Resistance in Crop Plants” (1951) proposed that plant resistance, as observed in the field, could be explained by three fundamental mechanisms which he named: (a) nonpreference, (b) antibiosis, and (c) tolerance. Painter and many subsequent workers have stressed the fact that these mechanisms are most frequently interrelated although they may also operate independently.