gebhart/patrepeval huggingface dataset:
Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans (2000)

<h3>BACKGROUND AND AIMS</h3> The mechanism of gastrointestinal damage (mucositis) induced by cancer chemotherapy remains uncertain. The aims of this study were to define the time course and mechanism of small intestinal damage following chemotherapy in humans. <h3>METHODS</h3> Patients receiving chemotherapy underwent upper gastrointestinal endoscopy (a maximum of two per patient) with duodenal biopsy prior to chemotherapy and again at 1, 3, 5, and 16 days after chemotherapy. Tissue was taken for morphometry, disaccharidase assays, electron microscopy, and for assessment of apoptosis using the Tdt mediated dUTP-biotin nick end labelling (TUNEL) method. Villus area, crypt length, and mitotic index were measured by a microdissection technique. <h3>RESULTS</h3> Apoptosis increased sevenfold in intestinal crypts at one day, and villus area, crypt length, mitotic count per crypt, and enterocyte height decreased at three days after chemotherapy. Disaccharidase activities remained unchanged. Electron microscopy showed increased open tight junctions of enterocytes at day 3, consistent with more immature cells. All indices improved by 16 days. <h3>CONCLUSION</h3> Small intestinal mucositis is associated with apoptosis in crypts that precedes hypoplastic villous atrophy and loss of enterocyte height.
A p53-Dependent Mouse Spindle Checkpoint (1995)

Cell cycle checkpoints enhance genetic fidelity by causing arrest at specific stages of the cell cycle when previous events have not been completed. The tumor suppressor p53 has been implicated in a G1 checkpoint. To investigate whether p53 also participates in a mitotic checkpoint, cultured fibroblasts from p53-deficient mouse embryos were exposed to spindle inhibitors. The fibroblasts underwent multiple rounds of DNA synthesis without completing chromosome segregation, thus forming tetraploid and octaploid cells. Deficiency of p53 was also associated with the development of tetraploidy in vivo. These results suggest that murine p53 is a component of a spindle checkpoint that ensures the maintenance of diploidy.
Substrate dependence on the optical properties of Al2O3 films grown by atomic layer deposition (1997)

The atomic layer deposition technique has been applied to the growth of Al2O3 thin films on the substrates of Si(100), 100-nm-thick SiO2 covered Si(100) [SiO2/Si(100)], and 90-nm-thick TiN covered SiO2/Si(100). The growth rate of Al2O3 films was 0.19 nm/cycle and identical for all substrates employed under the surface controlled process. However, the optical properties of Al2O3 films were significantly affected by different substrates. The average interband-oscillator energy and refractive index parameter were determined to be 3.330 eV and 2.992×10−14 eV m2 for Al2O3 film grown on Si(100), while those for the film grown on SiO2/Si(100) were 4.492 eV and 2.074×10−14 eV m2, respectively.
Testability modeling and analysis of a rocket engine test stand (2005)

This paper describes a testability analysis methodology that improves efficiency in maintainability and availability of a system, provides improvements in the overall capabilities of this system, and has historical verifiable data to compare the testability analysis metrics to the observed discrepancy reports. Here is a methodology that illustrates the use of a testability analysis tool to aid in the design and development of a health management system. Included is a brief discussion of how the model's testability output metrics can be used in conjunction with other types of model outputs for optimization purposes. Some top-level figures of merit are targeted here to verify that the testability analysis data is adequate and valid. It is shown here that this technology can improve maintenance efficiency, and aid in automating an integrated vehicle health management (IVHM) system, while reducing the need for human interaction for decision making, data acquisition and testing. The technology identifies critical components in the system, and prescribes a fast and accurate failure detection and isolation method that diagnoses faults to the lowest level of ambiguity. The safety, reliability and testability metrics identified here are used to reduce the test stand operator's stress levels by increasing the confidence in the operational state of the system, especially those related to critical components, before and during tests. Consequently, confidence in the test stand output data from the test article is realized. It is proven here that this technology also adds confidence in sustainability improvement of the test stand, which is above and beyond meeting just performance specifications. False alarms and false replacement concerns are also addressed here. The importance of using today's testability analysis tools for assessing and optimizing integrated vehicle health management systems is emphasized in this paper. With this technology we were able to model a rocket engine test stand and utilize the existing test stand sensors as a baseline for the testability analysis. We used the observed discrepancy maintenance reports provided by the test stand engineers to assign failure modes to the components.
A Multiubiquitin Chain Is Confined to Specific Lysine in a Targeted Short-Lived Protein (1989)

The ubiquitin-dependent degradation of a test protein β-galactosidase (βgal) is preceded by ubiquitination of βgal. The many (from 1 to more than 20) ubiquitin moieties attached to a molecule of βgal occur as an ordered chain of branched ubiquitin-ubiquitin conjugates in which the carboxyl-terminal Gly 76 of one ubiquitin is joined to the internal Lys 48 of an adjacent ubiquitin. This multiubiquitin chain is linked to one of two specific Lys residues in βgal. These same Lys residues have been identified by molecular genetic analysis as components of the amino-terminal degradation signal in βgal. The experiments with ubiquitin mutated at its Lys 48 residue indicate that the multiubiquitin chain in a targeted protein is essential for the degradation of the protein.
Coherent plane-wave compounding for very high frame rate ultrasonography and transient elastography (2009)

The emergence of ultrafast frame rates in ultrasonic imaging has been recently made possible by the development of new imaging modalities such as transient elastography. Data acquisition rates reaching more than thousands of images per second enable the real-time visualization of shear mechanical waves propagating in biological tissues, which convey information about local viscoelastic properties of tissues. The first proposed approach for reaching such ultrafast frame rates consists of transmitting plane waves into the medium. However, because the beamforming process is then restricted to the receive mode, the echographic images obtained in the ultrafast mode suffer from a low quality in terms of resolution and contrast and affect the robustness of the transient elastography mode. It is here proposed to improve the beamforming process by using a coherent recombination of compounded plane-wave transmissions to recover high-quality echographic images without degrading the high frame rate capabilities. A theoretical model is derived for the comparison between the proposed method and the conventional B-mode imaging in terms of contrast, signal-to-noise ratio, and resolution. Our model predicts that a significantly smaller number of insonifications, 10 times lower, is sufficient to reach an image quality comparable to conventional B-mode. Theoretical predictions are confirmed by in vitro experiments performed in tissue-mimicking phantoms. Such results raise the appeal of coherent compounds for use with standard imaging modes such as B-mode or color flow. Moreover, in the context of transient elastography, ultrafast frame rates can be preserved while increasing the image quality compared with flat insonifications. Improvements on the transient elastography mode are presented and discussed.
Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease (2009)

Hypercholesterolemia is one of the major causes of coronary heart disease (CHD). The genes encoding the low-density lipoprotein receptor and its ligand apolipoprotein B, have been the two genes classically implicated in autosomal dominant hypercholesterolemia (ADH). Our discovery in 2003 of the first mutations of the proprotein convertase subtilisin kexin 9 gene (PCSK9) causing ADH shed light on an unknown actor in cholesterol metabolism that since then has been extensively investigated. Several PCSK9 variants have been identified, some of them are gain-of-function mutations causing hypercholesterolemia by a reduction of low-density lipoprotein (LDL) receptor levels; while others are loss-of-function variants associated with a reduction of LDL-cholesterol (LDL-C) levels and a decreased risk of CHD. In this review, we focus on reported variants, and their biological, clinical, and functional relevance. We also highlight the spectrum of hypercholesterolemia or hypobetalipoproteinemia phenotypes that are already associated with mutations in PCSK9. Finally, we present future prospects concerning this therapeutic target that might constitute a new approach to reduce cholesterol levels and CHD, and enhance the effectiveness of other lipid-lowering drugs.
Generation of a strong mutator phenotype in yeast by imbalanced base excision repair (1998)

Increased spontaneous mutation is associated with increased cancer risk. Here, by using a model system, we show that spontaneous mutation can be increased several hundred-fold by a simple imbalance between the first two enzymes involved in DNA base excision repair. The Saccharomyces cerevisiae MAG1 3-methyladenine (3MeA) DNA glycosylase, when expressed at high levels relative to the apurinic/apyrimidinic endonuclease, increases spontaneous mutation by up to approximately 600-fold in S. cerevisiae and approximately 200-fold in Escherichia coli. Genetic evidence suggests that, in yeast, the increased spontaneous mutation requires the generation of abasic sites and the processing of these sites by the REV1/REV3/REV7 lesion bypass pathway. Comparison of the mutator activity produced by Mag1, which has a broad substrate range, with that produced by the E. coli Tag 3MeA DNA glycosylase, which has a narrow substrate range, indicates that the removal of endogenously produced 3MeA is unlikely to be responsible for the mutator effect of Mag1. Finally, the human AAG 3-MeA DNA glycosylase also can produce a small (approximately 2-fold) but statistically significant increase in spontaneous mutation, a result which could have important implications for carcinogenesis.
Roughened quartz surfaces and Teflon as small angle diffusers and depolarizers between 200 and 400 nm (1989)

Laboratory tests of transmission diffusers are reported for quartz and Teflon. These tests were conducted to select transmission diffusers for the NOAA rocket flight UV spectroradiometers.
A Comparative Analysis of Access Control Policy Modeling Approaches (2012)

Access control policies (ACPs) characterize the high-level rules according to which the access control of a system is regulated. Generally they are defined separately from the functional requirements (FRs) of an application and added to the system as an afterthought after being built. But, many problems arose during the integration of ACPs and FRs. Hence, over the past years, researchers have suggested for the modifying the design phase to include an earlier focus on access control issues through various modeling techniques. This paper reviews the important approaches in ACP modeling and makes a comparative analysis of the advantages and limitations of those techniques especially in addressing complex ACPs. Based on the comparative analysis, this paper presents directions for further work needed in handling the intricate nature of today’s ACPs.
Bacteriocins of lactic acid bacteria: extending the family (2016)

Lactic acid bacteria (LAB) constitute a heterogeneous group of microorganisms that produce lactic acid as the major product during the fermentation process. LAB are Gram-positive bacteria with great biotechnological potential in the food industry. They can produce bacteriocins, which are proteinaceous antimicrobial molecules with a diverse genetic origin, posttranslationally modified or not, that can help the producer organism to outcompete other bacterial species. In this review, we focus on the various types of bacteriocins that can be found in LAB and the organization and regulation of the gene clusters responsible for their production and biosynthesis, and consider the food applications of the prototype bacteriocins from LAB. Furthermore, we propose a revised classification of bacteriocins that can accommodate the increasing number of classes reported over the last years.
A multi-disciplinary Danish research programme on rainbow trout (Oncorhynchus mykiss) farming (1995)

A new research programme involving eight Danish institutions is described. The programme started in 1993 and is expected to run for 5 years. The primary objective of the research initiative is to exploit and integrate the knowledge of several institutions and disciplines for the benefit of the production of rainbow trout. The programme includes several projects with aspects of disease prevention, genetics, and nutrition. In most of the projects, the work has been divided into stages of 2 and 3 years, respectively. During a 2 year period, production, management, and health status are recorded at the participating fish farms, and all data are organized in a database. Diseases cause major problems in rainbow trout production, therefore a great deal of the effort in this programme deals with diseases caused by vira, bacteria and parasites. On the basis of the database, epidemiological examinations are carried out as well as investigations of the possibilities of preventive measures and cost-benefit analyses. In the genetic studies, polymorphic genetic markers will be developed and used for analysis of the genetic structure of selected fish stocks. Microsatellites will be developed and introduced in the study. Primarily genetic differences between lines/strains and their crossings will be estimated with the purpose of describing the genetic level and the importance of additive and non-additive genetic effects. In the nutritional area the product quality and pollution questions will be in focus.
Fundamentals of Coherent Optical Fiber Communications (2015)

The recently developed digital coherent receiver enables us to employ a variety of spectrally efficient modulation formats such as M-ary phase-shift keying and quadrature-amplitude modulation. Moreover, in the digital domain, we can equalize all linear transmission impairments such as group-velocity dispersion and polarization-mode dispersion of transmission fibers, because coherent detection preserves the phase information of the optical signal. This paper reviews the history of research and development related to coherent optical communications and describes the principle of coherent detection, including its quantum-noise characteristics. In addition, it discusses the role of digital signal processing in mitigating linear transmission impairments, estimating the carrier phase, and tracking the state of polarization of the signal in coherent receivers.
Weight Normalization: A Simple Reparameterization to Accelerate Training of Deep Neural Networks (2016)

We present weight normalization: a reparameterization of the weight vectors in a neural network that decouples the length of those weight vectors from their direction. By reparameterizing the weights in this way we improve the conditioning of the optimization problem and we speed up convergence of stochastic gradient descent. Our reparameterization is inspired by batch normalization but does not introduce any dependencies between the examples in a minibatch. This means that our method can also be applied successfully to recurrent models such as LSTMs and to noise-sensitive applications such as deep reinforcement learning or generative models, for which batch normalization is less well suited. Although our method is much simpler, it still provides much of the speed-up of full batch normalization. In addition, the computational overhead of our method is lower, permitting more optimization steps to be taken in the same amount of time. We demonstrate the usefulness of our method on applications in supervised image recognition, generative modelling, and deep reinforcement learning.
Self-Emulsifying Drug Delivery Formulations in the 21st Century: Challenges and Opportunities (2000)

In this chapter opportunities and challenges on the use of self-emulsifying drug delivery formulations for oral drug delivery and intestinal absorption enhancement are discussed. In the context of self-emulsifying formulations, the discussion includes both self-emulsifying drug delivery systems (SEDDS) and water-in-oil (W/O) microemulsions and case studies are presented where these systems have successfully been used to improve drug dissolution and oral absorption by overcoming solubility and membrane transport barriers. Drug development challenges such as excipient and vehicle selection, gelatin compatibility, physical and chemical stability, drug release, toxicity and safety, range of applicability and overall commercial viability are addressed. Future perspectives are discussed to further expand the application of these lipid drug carriers in oral drug delivery.
Kinetic and Calcium-Binding Properties of Three Calcium-Dependent Protein Kinase Isoenzymes from Soybean (1998)

Calmodulin-like domain protein kinases (CDPKs) are a family of calcium- but not calmodulin-dependent protein kinases found in a wide variety of plants and in protists. CDPKs are encoded by large multigene families, and to assess whether family members play distinct or redundant roles in vivo, we characterized soybean CDPK isoforms alpha, beta, and gamma, which share 60-80% identity in amino acid sequence. RNA blot analysis showed that the three CDPKs were expressed in most plant tissues examined and in suspension-cultured soybean cells. Recombinant CDPKalpha, -beta, and -gamma phosphorylated peptide substrates containing the four-residue motif R/K-X-X-S/T, but CDPKalpha was the most selective for residues outside of the motif. The CDPKs were inhibited by the general protein kinase inhibitors K252a and staurosporine and by calphostin C, which is an inhibitor of protein kinase C. The calcium-binding properties of each CDPK were distinct. The Kd's for Ca2+ determined by flow dialysis in the absence of substrates were 51, 1.4, and 1.6 micro M for CDPKalpha, -beta, and -gamma, respectively. In the presence of the peptide substrate syntide-2 the Kd of CDPKalpha decreased to 0.6 microM. Also, the sensitivity of this isoenzyme's activity to calcium varied with protein substrate. The concentrations of Ca2+ required for half-maximal activity (K0.5) for each CDPK with syntide-2 as substrate were 0.06, 0.4, and 1 micro M, respectively. These results show that members of the CDPK family differ in biochemical properties and support the hypothesis that each isoform may have a distinct role in calcium signal transduction.
NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid‐dependent childhood asthma (1999)

The relationship between nitric oxide in exhaled air, levels of sputum eosinophils, sputum eosinophil cationic protein (ECP) and urinary eosinophil protein X (EPX) excretion has not yet been investigated in corticosteroid-dependent childhood asthma. Therefore, taking 25 children with stable asthma (mean age 11.2 yrs) treated with inhaled corticosteroids and nine nonatopic healthy control children (mean age 12.8 yrs) the level of exhaled NO was measured by means of a chemiluminescence analyser before and after sputum induction. This was conducted as a slow vital capacity manoeuvre under standardized conditions with a target flow of 70 mL x s(-1) against a resistance of 100 cm H2O x L(-1) x s. Sputum induction was performed by inhalation of hypertonic saline (3, 4, and 5%) in a standardized manner and a single sample of urine was collected. Exhaled NO (p = 0.01), absolute eosinophil cell counts in sputum (p = 0.02), sputum ECP (p = 0.09) and urinary EPX excretion (p = 0.02) were higher in asthmatics compared to control children. Exhaled NO was positively correlated with sputum ECP (r(s) = 0.59, p = 0.002), urinary EPX (r(s) = 0.42, p = 0.03), and sputum eosinophils (r(s) = 0.30, p = 0.15) in the asthmatic children. These correlations appeared to be pronounced after sputum induction, where NO values had decreased (p = 0.01). None of the correlations were observed in the group of nonatopic control subjects. Additionally there were significant correlations between sputum ECP and sputum eosinophils (r(s) = 0.69, p<0.001) as well as between sputum ECP and urinary EPX excretion (r(s) = 0.58, p = 0.003) in the asthmatics. Exhaled NO provides information about the degree of eosinophilic airway inflammation and thus appears to be a useful and easy-to-perform inflammatory marker in corticosteroid-dependent asthma.
The Forgotten Serine (2000)

Previous work in the beta(2)-adrenergic receptor demonstrated critical interactions between Ser-204 and Ser-207 in the fifth membrane-spanning segment and the meta-OH and para-OH, respectively, of catecholamine agonists (Strader, C. D., Candelore, M. R., Hill, W. S., Sigal, I. S., and Dixon, R. A. (1989) J. Biol. Chem. 264, 13572-13578). Using the substituted cysteine accessibility method in the beta(2)-adrenergic receptor, we have found that in addition to Ser-204 and Ser-207, Ser-203 is also accessible on the surface of the binding-site crevice and is occluded by bound agonist. Mutation of Ser-203 to Ala, Val, or Cys reduced the binding affinity and adenylyl cyclase-activating potency of agonists containing a meta-OH, whereas their affinities and potencies were largely preserved by mutation of Ser-203 to Thr, which maintained an OH at this position. Thus both Ser-203 and Ser-204 appear to interact with the meta-OH of catecholamines, perhaps through a bifurcated H bond. Furthermore, the removal of the OH at position 203 led to a significant loss of affinity of antagonists with nitrogen in their heterocyclic ring structure. The greatest effect was seen with pindolol, a partial agonist, suggesting that a H bond between the heterocyclic ring and Ser-203 may play a role in partial agonism. In contrast, the affinities of antagonists such as propranolol or alprenolol, which have cyclic structures without H-bonding capability, were unaltered after mutation of Ser-203.
Automated Vertebra Detection and Segmentation from the Whole Spine MR Images (2005)

Our algorithm contains two major steps: the intervertebral disk localization step, and the vertebra detection and segmentation step. In the first step, we apply a model-based searching method to approximately locate all the intervertebral disk clues between adjacent vertebrae of the whole spine and the best slice selection. A new approach using an intensity profile on a polynomial function for fitting all these disk clues on the best slice is then used to refine the disk search process. Vertebra centers are detected, and initial boundaries are extracted in the second step. The initial test of the algorithm on the five sets of 7 sagittal slices locates all 23 intervertebral disk centers for the best slice of all five sets. For the evaluation of the boundary extraction of 22 vertebrae, our algorithm successfully locates 100%, 96.6%, 93.2%, 95.5%, 87.5% vertebra corners in image set No.1, 2, 3, 4, and 5, respectively.