gebhart/patrepeval huggingface dataset:
NINEPINS: Nuclei Instance Segmentation with Point Annotations (2020)

Deep learning-based methods are gaining traction in digital pathology, with an increasing number of publications and challenges that aim at easing the work of systematically and exhaustively analyzing tissue slides. These methods often achieve very high accuracies, at the cost of requiring large annotated datasets to train. This requirement is especially difficult to fulfill in the medical field, where expert knowledge is essential. In this paper we focus on nuclei segmentation, which generally requires experienced pathologists to annotate the nuclear areas in gigapixel histological images. We propose an algorithm for instance segmentation that uses pseudo-label segmentations generated automatically from point annotations, as a method to reduce the burden for pathologists. With the generated segmentation masks, the proposed method trains a modified version of HoVer-Net model to achieve instance segmentation. Experimental results show that the proposed method is robust to inaccuracies in point annotations and comparison with Hover-Net trained with fully annotated instance masks shows that a degradation in segmentation performance does not always imply a degradation in higher order tasks such as tissue classification.
Abuse Potential of Antiepileptic Drugs: a Review Using the VigiBaseTM Pharmacovigilance Database (P1.233) (2015)

OBJECTIVE:
Using a post-marketing pharmacovigilance database, to identify adverse events indicative of the abuse potential of the antiepileptic drugs (AEDs) carbamazepine (CBZ), oxcarbazepine (OXC), lacosamide (LCM), pregabalin (PGB), and eslicarbazepine acetate (ESL).
BACKGROUND:
VigiBase TM is the searchable World Health Organisation (WHO) Global Individual Case Safety Report database.
DESIGN/METHODS:
A custom search of the VigiBase TM database was conducted for each AED. MedDRA preferred terms associated with potentially abuse-related adverse events (AEs) were identified from Food and Drug Administration (FDA) presentations on AE terms indicative of abuse liability. The search period was 2008-2011, except ESL, which, due to its more recent European approval, was 2010-2011. The incident rate per 100 patient-years exposure was determined (exposure was calculated from prescription data [number of retail doses sold in 13 European countries] and the assumed mean daily dose of each AED).
RESULTS:
Potentially abuse-related AEs were reported more frequently with LCM and PGB than with CBZ, OXC, and ESL. Specific indicators of abuse were reported infrequently; maximum rates (highest incident rate per 100 patient-years reported for any year in the search period for each AED) for CBZ, OXC, LCM, PGB, and ESL, respectively were:
Euphoric mood: 0.03, 0.3, 3.25, 4.15, no reports (NR)
Hallucination: 0.30, 1.03, 9.96, 8.58, NR
Drug dependence: 0.03, 0.1, 0.71, 3.07, NR
Drug abuse: 0.09, 0.51, NR, 1.81, NR
Withdrawal syndrome: 0.14, 0.21, NR, 6.14, NR
CONCLUSIONS:
Abuse-related AEs (including specific indicators of abuse potential, such as euphoria and hallucinations) were reported more frequently for LCM and PGB than CBZ, OXC, and ESL. However, as pharmacovigilance databases are based on spontaneous reporting, these findings may underestimate the actual incidence of these AEs in the clinic.
				
				 Disclosure: Dr. Gidal has received personal compensation for activities with GlaxoSmithKline, UCB Pharma, Eisai, Sunovian, and Upsher Smith Laboratories, Inc. as a consultant and/or speaker. Dr. Gidal has received research support from GlaxoSmithKline and UCB Pharma. Dr. Blum has received personal compensation for activities with Sunovion Pharmaceuticals Inc. as an employee.
A Correlative Light and Electron Microscopy Method Based on Laser Micropatterning and Etching (2008)

Correlative microscopy is a hybrid method that allows the localization of events observed under visible, ultraviolet, or infrared light, at molecular and submolecular levels, combining two microscopy techniques. However, the main limitation of correlative microscopy is to develop a labeling technique that can be easily used first in light and then in electron microscopy. Laser etching is a well-established method to create precisely designed shapes or volumes in various materials including glass. We have applied this technique to develop a new correlative light and electron microscopy method and to apply it in our study of the Golgi apparatus. The location of the cell of interest is laser-inscribed into the glass allowing a simple follow-up in light and fluorescence microscopy. Furthermore, the glass surface is laser-etched and upon fixation and flat embedding, the inverse ridge can be localized as well as the cell of interest, which is then processed for electron microscopy.
Synthesis of syn and anti isomers of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-2-amine. Inhibitors of rhinovirus multiplication (1980)

The synthesis and antirhinovirus activity of syn and anti isomers of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-2-amine (4 and 5) are reported. The structural assignments of 4 and 5 are based upon 13C NMR spectra of both isomers and also X-ray analysis of 5. The anti-isomer 5 was more potent than the syn-isomer 4 when compared as an inhibitor of rhinovirus multiplication in vitro. Both isomers inhibited multiplication of 15 different serotypes of rhinovirus.
The collisional limit: an important consideration for membrane‐associated enzymes and receptors (1988)

Because of the proximity of many bound receptors or enzymes, a membrane surface may become uniformly reactive so that every collision between a ligand and the membrane particle results in a binding or catalytic event. At this limit (the collisional limit), the reaction rate depends on membrane particle (cell) concentration and is independent of receptor concentration. Many receptor systems display properties that satisfy the requirements of a collisionally limited reaction. These include the presence of many receptors per cell. The filling of only a few of these receptors often generates the maximum cellular response, and the remaining receptors have been referred to as spare receptors. However, many receptors are needed to produce the collisional limit, and spare receptors may represent nature's evolution toward a reaction that provides the maximum rate as well as the maximum sensitivity to a ligand. Since receptors or enzymes provided on small membrane fragments will not function at the collisional limit, properties of reconstituted enzymes or receptors may not be extrapolated to the physiological situation. The use of normal bimolecular kinetic or equilibrium equations is inappropriate for reactions limited by collision and can give unusual results that lead to inappropriate conclusions. Determination of whether the collisional limit applies to a membrane-bound system is important for understanding its properties and those of the physiological circumstance.
Kinetic studies of the association of complement components and IgG-coated latex particles incubated in normal or complement-activated human serum. (1981)

The complement components C1q, C1s, C4 and C3 were instantly associated with IgG-coated latex particles incubated in fresh but not heated (56°C, 30 min) NHS and were detectable as a particle agglutination induced by antibodies to these complement subcomponents. The agglutination reactions were studied kinetically utilizing aggregation equipment. After about 60 sec of incubation of the particles with NHS, no C1s antigenic determinants were detectable on the particles. C1q also became less particle-associated during a 2-min incubation as judged from the decline in particle agglutination. These findings suggest a complete dissociation of C1s and a partial dissociation of C1q from IgG complexes incubated in fresh NHS. The proposed discharge of C1q but not C1s was dependent on Mg(++), prevented by dilution of serum and not observed when IgG particles were incubated in serum previously exposed to inulin. Both C1q and C1s remained particle-associated when IgG particles were incubated in sera activated in vitro or in vivo according to the classical pathway. These findings may indicate that the normal behaviour of C1q, but not that of C1s, after their initial binding to IgG complexes, is dependent upon components of the alternative pathway. C4 and C3 remained particle-associated after their initial binding to the IgG particles. Although C4 was antigenically detectable on the particles after longer incubation with serum, the patterns of the C4-dependent agglutination changed with time, which may reflect changes in the molecular arrangement of C4 after its initial binding to IgG complexes. The changes in the C4-dependent agglutination reactions were dependent on the alternative pathway. No or reduced binding of C3 to IgG particles was found when IgG particles were incubated in sera containing C3 in a mainly activated form after complement activation according to either pathway. Neither became C4 particle-associated when completely converted. C5 antigenic determinants were not detectable on IgG particles incubated in fresh NHS but were found in NHS activated according to the classical but not the alternative pathway.
Design and fabrication of air-flow based single particle dispensing system (2011)

In this paper, we discuss the design and fabrication approach to increase the success rate of single particle dispensing. Two pairs of capacitance sensors are placed in a biochip to detect the flow velocity of particles, and the air pressure is applied to eject particles by synchronizing the timing. Comprehensive design theory, which is taken into account of the back pressure caused by air pressure, the response time of the system, sensor property, and the delay of the dispensing from the air pressure, is developed in order to minimize the disturbance of the system and maximize the throughput of the ejection system. Then, the system has capability to eject 3 particles/sec and maximum flow velocity is 10 mm/s. The novelty of the system is that the biochip is disposable which is unlike the conventional mechanical inkjet system and it can prevent contamination. Therefore, the fabricated disposable biochip based on photolithography is low cost and the drive system is reusable. Finally, we succeed in automatic dispensing of a single particle (=100 µm) from a biochip to culture well atmosphere using developed cell ejection system with the success rate of 50 %.
Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation (1997)

Aerobic exercise improves the physical performance of cancer patients recovering from high dose chemotherapy. To reduce fatigue, this group of patients should be counseled to increase physical activity rather than rest after treatment.
A computer based data acquisition system for teaching transients and switching phenomena and performing research on digital protection (1988)

The authors present a computer-based model for demonstrating and teaching fault-induced transients, switching phenomena, and power with particular reference to teaching and advancing the concepts of digital protection of power systems. The design and implementation of a digitally controlled switching circuit is described. A data-acquisition system for sampling the current and voltage waveforms used in conjunction with a special interface with a VAX 11/750 or a personal computer to analyze the data is presented. An example of qualitative study for inrush current and fault-induced transients in a power transformer is shown. A mathematical model for the inrush current in a power transformer that accounts for time-varying and random parameters and that offers a basis for developing methods for digital protection of power transformers is presented. Finally, the integration of the model in teaching senior and graduate-level subjects related to power-system transients and protection is summarized.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The application of big data to cardiovascular disease: paths to precision medicine (2020)

Advanced phenotyping of cardiovascular diseases has evolved with the application of high-resolution omics screening to populations enrolled in large-scale observational and clinical trials. This strategy has revealed that considerable heterogeneity exists at the genotype, endophenotype, and clinical phenotype levels in cardiovascular diseases, a feature of the most common diseases that has not been elucidated by conventional reductionism. In this discussion, we address genomic context and (endo)phenotypic heterogeneity, and examine commonly encountered cardiovascular diseases to illustrate the genotypic underpinnings of (endo)phenotypic diversity. We highlight the existing challenges in cardiovascular disease genotyping and phenotyping that can be addressed by the integration of big data and interpreted using novel analytical methodologies (network analysis). Precision cardiovascular medicine will only be broadly applied to cardiovascular patients once this comprehensive data set is subjected to unique, integrative analytical strategies that accommodate molecular and clinical heterogeneity rather than ignore or reduce it.
Product creativity assessment of innovations: considering the creative process (2014)

Creativity is a critical component that feeds into all stages of innovation and design processes by promoting inspiration, ideation, and implementation of ideas, revealing the need for thorough research to support design creativity. Assessment of product creativity is a reoccurring topic in creativity research, while the role of consumer's knowledge of the creative process behind the product is fairly unexplored. In this paper, we present an empirical study investigating whether providing information about a complex development process could amplify consumer's perception of product creativity. Does storytelling about the process contribute to amplifying creativity ratings? What form of storytelling is needed to make an impact? Results from 134 respondents showed a small but not significant amplifying effect from the additional process information; however, an important learning can be drawn about the form of storytelling needed. An absolute minimal form was chosen here, displaying the need for investigating other, more elaborate forms. Additionally, the analysis showed that creativity was an important driver for the assessment of other product attributes such as purchasability, portraying the importance of design creativity and underlining the importance of further investigating the role of creative process information in amplifying consumer's perception of creativity in products.
Atomistic and Continuum Understanding of the Particle Clustering and Particle Size Effect on the Room and High Temperature Strength of SiC-Si3N4 Nanocomposites (2010)

Silicon carbide (SiC)-silicon nitride (Si3N4) nanocomposites are one of the most important high temperature materials. Factors that affect the strength of the SiC-Si3N4 nanocomposites can include the second phase SiC particle placement and clustering along Si3N4 GBs, the SiC particle size, Si3N4 grain size, and Si3N4 matrix morphology. This work presents recent work by our group in analyzing the effect of morphological variations in second phase SiC particle placement and GB strength on the room temperature fracture strength of SiC-Si3N4 nanocomposites using continuum analyses based on a mesoscale (~50 nm) cohesive finite element method (CFEM) and using molecular dynamics (MD) based analyses at nanoscale (~15 nm). The analyses have revealed that high strength and relatively small sized SiC particles act as stress concentration sites in Si3N4 matrix leading to inter-granular Si3N4 matrix cracking as a dominant nanocomposite failure mode under dynamic loading. At high SiC volume fractions that peak at approximately 30%, the CFEM analyses have revealed that due to a significant number of nano-sized SiC particles being present in micro-sized Si3N4 matrix, the SiC particles invariantly fall in the wake regions of microcracks leading to significant increase in fracture resistance. This finding was mechanistically confirmed in the room temperature MD analyses that revealed that particle clustering along the GBs was more effective than particles being placed on GBs in increasing the nanocomposite mechanical strength. The temperature dependent deformation mechanism is found to be a trade-off between the stress concentration caused by SiC particles and Si3N4-Si3N4 GB sliding. The temperature increase tends to work in favor of GB sliding leading to softening of structures. However, microstructural strength increases with increase in temperature when GBs are absent.
Root Deformation Reduces Tolerance of Lodgepole Pine to Attack by Warren Root Collar Weevil (2010)

Surveys were conducted on regenerating stands of lodgepole pine to determine the relationship between root deformation and susceptibility to attack by the Warren root collar weevil, Hylobius warreni Wood. The total number of trees attacked by H. warreni did not differ between planted and natural trees. A matched case-control logistic regression suggested that root cross-sectional area was more important in predicting weevil attack for naturally regenerated trees than for planted trees, but weevils were associated with a larger reduction in height-to-diameter ratios for trees with planted root characteristics than for trees with natural root form. Neither the stability of attacked versus unattacked trees differed significantly and there was no significant interaction of weevil attack and tree type, but weevil-killed trees had different root characteristics than alive, attacked trees. Lateral distribution and root cross-sectional area were significant predictors of alive attacked trees versus weevil-killed trees, suggesting that trees with poor lateral spread or poor root cross-sectional area are more likely to die from weevil attack. We conclude that root deformation does not necessarily increase susceptibility to attack but may increase the likelihood of mortality. Thus, measures to facilitate good root form are needed when planting pine in areas with high risk of Warren root collar weevil attack.
A six‐microRNA risk score model predicts prognosis in esophageal squamous cell carcinoma (2018)

Esophageal cancer ranks the eighth most common cancer and the sixth most common cause of cancer death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate a wide variety of cancer-related cellular processes. In the current study, a series of previously published gene expression microarray data from Gene Expression Ominus and The Cancer Genome Atlas were downloaded and further divided into training, internal, and external validation sets. Least absolute shrinkage and selectionator operator Cox regression model along with 10-fold cross-validation was performed to select the miRNAs associated with the prognosis of esophageal squamous cell carcinoma (ESCC) and constructed a six-miRNA signature. Then the prediction accuracy of this signature was assessed in validation and test set using Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) curves and dynamic area under the ROC curve. According to the result, the prediction accuracy of miRNA signature was much better than that of tumor-node-metastasis (TNM) stage in all the three sets. Stratified analysis also demonstrated that the predict ability of this signature was independent of TNM stage. Finally, function experiments including apoptosis and colony formation assay were performed to further reveal the regulatory role of miRNAs in ESCC. Our study demonstrated the promising potential application of this novel six-miRNA signature as an independent biomarker for survival prediction of ESCC patients.
A novel dual‐frequency dual‐polarized stacked patch microstrip array feed for remote sensing reflector antennas (2006)

Abstract This paper presents the design and implementation of a dual‐frequency dual‐linear polarized stacked patch array feed with a novel probe‐feeding architecture for future spaceborne synthetic aperture radar (SAR) applications. To facilitate measurements of soil moisture from space, a large aperture antenna of 30 m operating in VHF (137.5 MHz) and UHF (435 MHz) frequencies is desirable. An array feed that synthesizes a rectangular effective aperture on the 30‐m reflector is proposed in order to obtain matched beams at the VHF and UHF frequencies. We focus on the layout, design, and prototype performance of the stacked‐patch microstrip array designed for scaled operating frequencies of 1.13 GHz (lower patch) and 3.57 GHz (upper patch). The study is also aimed at analyzing the performance of the array in combination with a 3.65‐m reflector. Our test results demonstrate a good correlation between the measurements and simulations from finite‐difference time domain (FDTD) and reflector analysis codes, thus validating the design for use in SAR for soil‐moisture applications. © 2006 Wiley Periodicals, Inc. Microwave Opt Technol Lett 48: 1250–1258, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.21669
Regulation of the Bacillus anthracis protective antigen gene: CO2 and a trans-acting element activate transcription from one of two promoters (1994)

The pag gene of Bacillus anthracis, located on plasmid pXO1 (185 kb), encodes protective antigen, a component of the anthrax lethal and edema toxins. Synthesis of protective antigen is enhanced during growth of the organism with elevated levels of CO2. The CO2 effect is at the level of transcription, and pXO1-encoded regulatory factors have been implicated in control of pag expression. We used a Tn917-LTV3 insertion mutant of B. anthracis in which the wild-type pag gene on pXO1 was replaced with a pag-lacZ transcriptional fusion to monitor pag promoter activity. Expression of the pag-lacZ fusion is induced five- to eightfold during growth in 5% CO2 compared with growth in air. Growth in 20% CO2 increases transcription up to 19-fold. By monitoring pag-lacZ expression in atmospheres with different O2 and CO2 concentrations, we demonstrated definitively that the CO2 effect is specific and not simply a result of increased anaerobiosis. The results of 5' end mapping of pag transcripts indicate multiple sites of transcript initiation. We have determined two major apparent start sites, designated P1 and P2, located at positions -58 and -26 relative to the translation initiation codon, respectively. Analysis of total RNA from late-log-phase cells shows comparable initiation from P1 and P2 in wild-type strains grown in aerobic conditions. However, initiation from P1 is increased approximately 10-fold in cultures grown with an elevated level (5%) of CO2. We have identified a locus on pXO1, more than 13 kb upstream from the pag gene, which enhances pag transcription. When added in trans, this locus increases the level of transcripts with 5' ends mapping to P1 but has no effect on the level of transcripts with 5' ends mapping to P2. The CO2 effect on P1 is observed only in the presence of the activator locus.
[Alternative filling methods for premolars and molars]. (1989)

Extensive research and development work produced tooth-colored filling materials for premolars and molars which, although their indications are limited, provide for satisfactory treatment of cavities. But on account of their special properties these materials are unlikely to replace amalgam altogether. This would need products of a different nature. Currently available materials are at best complementary, but cannot be regarded as a true alternative.