gebhart/patrepeval huggingface dataset:
3Rs‐friendly approach to exogenous metabolic activation that supports high‐throughput genetic toxicology testing (2020)

MultiFlow® DNA Damage-p53, γH2AX, Phospho-Histone H3 is a miniaturized, flow cytometry-based assay that provides genotoxic mode of action information by distinguishing clastogens, aneugens, and nongenotoxicants. Work to date has focused on the p53-competent human cell line TK6. While mammalian cell genotoxicity assays typically supply exogenous metabolic activation in the form of concentrated rat liver S9, this is a less-than-ideal approach for several reasons, including 3Rs considerations. Here, we describe our experiences with low concentration S9 and saturating co-factors which were allowed to remain in contact with cells and test chemicals for 24 continuous hours. We exposed TK6 cells in 96-well plates to each of 15 reference chemicals over a range of concentrations, both in the presence and absence of 0.25% v/v phenobarbital/β-naphthoflavone-induced rat liver S9. After 4 and 24 hr of treatment cell aliquots were added to wells of a microtiter plate containing the working detergent/stain/antibody cocktail. After a brief incubation robotic sampling was employed for walk-away flow cytometric data acquisition. PROAST benchmark dose (BMD) modeling was used to characterize the resulting dose-response curves. For each of the 8 reference pro-genotoxicants studied, relative nuclei count, γH2AX, and/or p53 biomarker BMD values were order(s) of magnitude lower for 0.25% S9 conditions compared to 0% S9. Conversely, several of the direct-acting reference chemicals exhibited appreciably lower cytotoxicity and/or genotoxicity BMD values in the presence of S9 (eg, resorcinol). These results prove the efficacy of the low concentration S9 system, and indicate that an efficient and highly scalable multiplexed assay can effectively identify chemicals that require bioactivation to exert their genotoxic effects.
Process Characteristics of Laser Brazing Aluminium Alloys (2005)

Compared to welding, laser brazing offers a suitable possibility to lower the working temperature and to join unweldable material combinations, while maintaining the numerous advantages of the laser joining process. Beside an acceptable joint strength, the brazed joints are characterised by a smooth surface and seams with almost no pores. As a result of this laser brazing combines the advantages of conventional brazing and laser welding. Within the scope of this paper the laser brazing process and its characteristics are explained in detail. In particular the interrelation of temperature progress, available processing time for brazing/diffusion and the thickness of the diffusion layer is discussed. Subsequently the material specific particularities of laser brazing aluminium alloys are described and discussed with respect to recently gained results.
Antimony Telluride Formation Hypothesized from Reactor Coolant System Sample Data (1986)

"Antimony Telluride Formation Hypothesized from Reactor Coolant System Sample Data." Nuclear Technology, 73(1), pp. 125–126
Inconclusive rate in quantum key distribution (2002)

Summary form only given. The inconclusive rate can be a useful disturbance measure in quantum cryptography. Bennett's two-state protocol is considered for the case in which a positive operator-valued measure is optically implemented by the legitimate receiver in the presence of an individual attack by a general unitary disturbing eavesdropping probe. The maximum Renyi information gain by the disturbing probe is calculated for given receiver error and inconclusive rates. It is shown explicitly that less information is available to an eavesdropper at fixed inconclusive rate and error rate than is available at fixed error rate only.
[Selective brushings for all branches of the bronchi: diagnostic values thereof in patients with roentgenographically occult lung cancer and borderline lesions]. (1989)

Selective brushings were conducted for all the respective segmental bronchi in both lungs of 105 patients with positive or suspected positive indications of lung cancer as revealed by sputum cytology. As a result, borderline lesions, 16 cases with 18 lesions and lung cancer, 51 cases with 58 lesions, were diagnosed. The percentage of localized lesions was 47.1% for Class III cases, 82.4% for Class IV cases and 100% for Class V cases; on the whole, identification was possible in 62.9% of all the cases. Comparison of the diagnoses made before and after all the branch brushings showed that, after the brushings, the rate of localization increased from 14.7% to 47.1%, and diagnosis of borderline lesions is also possible. Regarding the results obtained at the first examination, the rate of localization increased from 64.1% to 93.9%, and in particular, an improvement from 0% to 88.9% was noted for those cases where bronchoscopic findings had not been obtained. Based on the above results, it was concluded that the application of this brushing method is of value in the following cases: diagnosis of cases otherwise difficult to diagnose, detection of borderline lesions, and diagnosis of concurrent multiple primary lung cancer. In addition, this brushing method has made possible the detection of multiple intraepithelial lesions, leading to a more precise diagnosis of cells of the respiratory system in the near future.
Increased Ratios of Internal Organ Volume to Body Mass in Chuvash Polycythemia and HIF-2α Repression of p21Cip Expression through C-MYC. (2009)

Abstract Abstract 5039 Chuvash polycythemia, the first hereditary disease associated with dysregulated oxygen sensing, is characterized by homozygous germ-line loss-of-function mutation of VHL (598C&gt;T) resulting in elevated hypoxia inducible factor (HIF)-1 and HIF-2 levels, increased red cell mass and propensity to thrombosis. Organ size is determined by the size and number of cells, and its molecular mechanisms are not fully elucidated. Previous work from several groups demonstrated that cell proliferation is regulated in opposite directions by HIF-1α and HIF-2α. HIF-1α inhibits cell proliferation by displacing C-MYC from the promoter of the cyclin-dependent kinase inhibitor, p21Cip, and inducing its expression, while HIF-2α promotes MYC activity and cell proliferation. We determined the volumes of the liver, spleen, and kidneys and the diameter of the head of the pancreas by computerized tomography in 30 individuals with Chuvash polycythemia and 30 age- and sex-matched Chuvash controls and calculated the ratio of organ volume (or diameter) to body mass. The subjects with Chuvash polycythemia had larger ratios of the liver (P&lt;0.01), spleen (P&lt;0.01), kidneys (P&lt;0.05) and head of the pancreas (P=0.05) than Chuvash controls. To test if HIF contributes to this phenotype, we examined Hif1a+/− mice and wild type littermates. We found that Hif1a+/− mice had larger median ratios of liver to body mass (factor of 1.5, P&lt;0.005) and pancreas to body mass (factor of 1.3, P&lt;0.05) than wild type mice. A hepatocyte size analysis revealed that there was no significant difference between Hif1a+/− and wild type mice. To identify how HIF contributes this phenotype, we performed gene expression profiles in the livers of Hif1a+/− and wild type littermates. The profiling results and subsequent individual confirmation showed that compared to wild type mice, Hif1a+/− mice had 2-fold higher HIF-2α mRNA levels (P&lt;0.05) and 9.5-fold lower hepatic p21Cip mRNA levels (P&lt;0.05). Our results showed that relative to body mass, liver, spleen, kidney and pancreas volumes are increased in Chuvash polycythemia. At least in the liver, this phenotype may result from increased HIF-2α and decreased p21Cip1 levels, leading to increased hepatocyte proliferation. Disclosures No relevant conflicts of interest to declare.
Religion (2017)

That religion should be a researchers’ “taboo topic” in the mid-twentieth century would have surprised social scientists in the first quarter of the century. The psychology of religion seemed then off to a good beginning in the pioneer work of Hall, Starbuck, Coe, Pratt, and Leuba and was widely “advertised” in the 1901-1902 Gifford Lectures of William James on The Varieties of Religious Experience. Great theoretical contributions were being made by Durkheim and Weber in sociology of religion and by Radcliffe-Brown and Malinowski in social anthropology. Studies by Tylor and Frazer of primitive religion and its symbolic artifacts stimulated much interest. Provocative theses had been advanced and conceptual models had been made available for further testing and refinement. Since the end of World War II, however, the Zeitgeist has been changing rapidly. There are many indications of a new climate. Though at some points his operational definitions appear inadequate, G. Lenski’s study represents great advances in conceptual clarity.
Crosspolarisation characteristics of circular patch antennas (1992)

The crosspolarisation characteristics of coaxially fed microstrip patch antennas are studied using the cavity model. Numerical results showing the variation of crosspolarisation level for different feed positions, substrate thicknesses, substrate permittivities and resonance frequencies are given when the antenna is excited in the TM11 mode.
Multiple harmonic conversion of pulsed CO 2 laser radiation in Ti 3 AsSe 3 (1988)

The near-infrared region is of importance in areas such as photochemistry, optical communications, and optical pumping; yet it remains relatively uncovered by strong coherent sources of radiation. The CO2 laser is an efficient and tunable source of mid-IR radiation, and as a result frequency conversion of CO2 lasers in nonlinear materials is an attractive method for generating new IR sources. Thallium arsenic selenide (TI3AsSe3) (TAS) is a birefringent ternary chalcogenide salt with many properties that are useful for CO2 harmonic generation. It is a member of the space group R3m, possesses a large nonlinear coefficient (deff = 40 X 10−12 m/V), has a fairly high damage threshold (1.7 J/cm2), and is transparent and phase-matchable throughout the IR. Under type I phase matching, high second harmonic conversion efficiencies of CO2 laser radiation have been measured in the present study, and conversion of the CO2 fundamental into its third, fourth, and fifth harmonic has been achieved for the first time.
Modeling of Dynamic Fracture and Damage in Two-Dimensional Trabecular Bone Microstructures Using the Cohesive Finite Element Method (2008)

Trabecular bone fracture is closely related to the trabecular architecture, microdamage accumulation, and bone tissue properties. Micro-finite-element models have been used to investigate the elastic and yield properties of trabecular bone but have only seen limited application in modeling the microstructure dependent fracture of trabecular bone. In this research, dynamic fracture in two-dimensional (2D) micrographs of ovine (sheep) trabecular bone is modeled using the cohesive finite element method. For this purpose, the bone tissue is modeled as an orthotropic material with the cohesive parameters calculated from the experimental fracture properties of the human cortical bone. Crack propagation analyses are carried out in two different 2D orthogonal sections cut from a three-dimensional 8 mm diameter cylindrical trabecular bone sample. The two sections differ in microstructural features such as area fraction (ratio of the 2D space occupied by bone tissue to the total 2D space), mean trabecula thickness, and connectivity. Analyses focus on understanding the effect of the rate of loading as well as on how the rate variation interacts with the microstructural features to cause anisotropy in microdamage accumulation and in the fracture resistance. Results are analyzed in terms of the dependence of fracture energy dissipation on the microstructural features as well as in terms of the changes in damage and stresses associated with the bone architecture variation. Besides the obvious dependence of the fracture behavior on the rate of loading, it is found that the microstructure strongly influences the fracture properties. The orthogonal section with lesser area fraction, low connectivity, and higher mean trabecula thickness is more resistant to fracture than the section with high area fraction, high connectivity, and lower mean trabecula thickness. In addition, it is found that the trabecular architecture leads to inhomogeneous distribution of damage, irrespective of the symmetry in the applied loading with the fracture of the entire bone section rapidly progressing to bone fragmentation once the accumulated damage in any trabeculae reaches a critical limit.
Projector'S Weighting For W-Music: An Alternative To Rmt (2018)

Publication in the conference proceedings of EUSIPCO, Kos island, Greece, 2017
Integrin β1 Signaling Is Necessary for Transforming Growth Factor-β Activation of p38MAPK and Epithelial Plasticity (2001)

Transforming growth factor-beta (TGF-beta) can induce epithelial to mesenchymal transdifferentiation (EMT) in mammary epithelial cells. TGF-beta-mediated EMT involves the stimulation of a number of signaling pathways by the sequential binding of the type II and type I serine/threonine kinase receptors, respectively. Integrins comprise a family of heterodimeric extracellular matrix receptors that mediate cell adhesion and intracellular signaling, hence making them crucial for EMT progression. In light of substantial evidence indicating TGF-beta regulation of various beta(1) integrins and their extracellular matrix ligands, we examined the cross-talk between the TGF-beta and integrin signal transduction pathways. Using an inducible system for the expression of a cytoplasmically truncated dominant negative TGF-beta type II receptor, we blocked TGF-beta-mediated growth inhibition, transcriptional activation, and EMT progression. Dominant negative TGF-beta type II receptor expression inhibited TGF-beta signaling to the SMAD and AKT pathways, but did not block TGF-beta-mediated p38MAPK activation. Interestingly, blocking integrin beta(1) function inhibited TGF-beta-mediated p38MAPK activation and EMT progression. Limiting p38MAPK activity through the expression of a dominant negative-p38MAPK also blocked TGF-beta-mediated EMT. In summary, TGF-beta-mediated p38MAPK activation is dependent on functional integrin beta(1), and p38MAPK activity is required but is not sufficient to induce EMT.
Human embryonic stem cell-derived motor neurons expressing SOD1 mutants exhibit typical signs of motor neuron degeneration linked to ALS (2009)

Human embryonic stem cell (hESC)-derived neurons have the potential to model neurodegenerative disorders. Here, we demonstrate the expression of a mutant gene, superoxide dismutase 1(SOD1), linked to familial amyotrophic lateral sclerosis (ALS) in hESC-derived motor neurons. Green fluorescent protein (GFP) expression under the control of the HB9 enhancer was used to identify SOD1-transfected motor neurons that express human wild-type SOD1 or one of three different mutants (G93A, A4V and I113T) of SOD1. Neurons transfected with mutant SOD1 exhibited reduced cell survival and shortened axonal processes as compared with control-transfected cells, which could survive for 3 weeks or more. The results indicate that hESC-derived cell populations can be directed to express disease-relevant genes and to display characteristics of the disease-specific cell type. These genetically manipulated hESC-derived motor neurons can facilitate and advance the study of disease-specific cellular pathways, and serve as a model system to test new therapeutic approaches.
Study of a possible X-ray sensor based on the Plasmon Surface Resonance for the next generation of instruments (2011)

peer reviewed
The Dihydroorotate Dehydrogenase Inhibitor Brequinar Is Synergistic with ENT1/2 Inhibitors (2020)

The dihydroorotate dehydrogenase (DHODH) inhibitor brequinar failed all clinical trials for solid tumors. To investigate mechanisms to increase brequinar's efficacy, we employed a combination strategy to simultaneously inhibit the nucleotide salvage pathways. Brequinar is synergistic with the equilibrative nucleoside transporter (ENT) inhibitor dipyridamole, but not the concentrative nucleoside transporter inhibitor phlorizin. This synergy carries over to ENT1/2 inhibition, but not ENT4. Our previously described brequinar analogue <b>41</b> was also synergistic with dipyridamole as were the FDA-approved DHODH inhibitors leflunomide and teriflunomide but the latter required much higher concentrations than brequinar. Therefore, a combination of brequinar and ENT inhibitors presents a potential anti-cancer strategy in select tumors.
Theoretical Analysis of Unidirectional Operation and Reflection Sensitivity of Semiconductor Ring or Disk Lasers (2013)

We theoretically and numerically analyze the unidirectional behavior of ring or disk lasers coupled to a bus waveguide with a relatively strong reflector on one side and find analytical expressions for the ratio of the powers in clockwise and counter clockwise modes. At low bias levels, this ratio depends on the coupling coefficients that determine the coupling between clockwise and counterclockwise modes, whereas at high bias levels it also depends strongly on the gain suppression. We also theoretically and numerically investigate the feedback sensitivity of such lasers and come to the conclusion that ring or disk lasers are generally much more sensitive to external reflections than traditional Fabry-Perot, DFB, or DBR lasers. At high bias levels, the feedback sensitivity also depends strongly on the gain suppression, and at high enough power levels, it can be better than that of traditional edge-emitting lasers.
Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing (2019)

6-(4-(Diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2<i>H</i>)-one, or <b>DNMDP</b>, potently and selectively inhibits phosphodiesterases 3A and 3B (PDE3A and PDE3B) and kills cancer cells by inducing PDE3A/B interactions with SFLN12. The structure-activity relationship (SAR) of <b>DNMDP</b> analogs was evaluated using a phenotypic viability assay, resulting in several compounds with suitable pharmacokinetic properties for <i>in vivo</i> analysis. One of these compounds, <b>BRD9500</b>, was active in an SK-MEL-3 xenograft model of cancer.
Ultrastrong coupling with few (<60) electrons at 280 GHz in single LC nanogap resonators (Conference Presentation) (2017)

Strong light-matter coupling lies at the heart of quantum optics and recently has been successfully explored also in the GHz and THz range. New, intriguing quantum optical phenomena have been predicted in the ultrastrong coupling regime, when the coupling strength Omega becomes comparable to the unperturbed frequency of the system omega_c. We recently proposed a new experimental platform where the physics of the ultrastrong coupling can be investigated at GHz-THz frequencies. We couple the inter-Landau level transition of an high-mobility 2 dimensional electron gas (2DEG) to the subwavelength photonic mode of an LC meta-atom. Our system benefits from the collective enhancement of the light-matter coupling which comes from the scaling of the coupling constant Omega with the square root of the number of electrons in the last Landau level. In our previous experiments and in literature this number varies from 10000-1000 electrons per resonator. Here we present ultrastrong coupling between a high-mobility 2DEG (mu=2.3X 10^6 cm^2/Vs) and an extremely subwavelength hybrid-LC resonator ensemble (11 resonators) with an highly reduced effective mode volume V_eff=4 x 10^-19 m^3=4 x 10^(-10) lambda^3 at a frequency of 300 GHz. The number of optically active electrons is given by the flux quantum multiplied by the effective resonator area and is proportional to the magnetic field. At the anticrossing field of B=0.73 T we measure less than 80 electrons ultrastrongly coupled to the resonator with a normalized coupling ratio Omega/omega_c=0.35. This experiment paves the way towards the study of ultrastrong coupling physics in the regime of quantum non-linearities.
Axon initial segment dysfunction in epilepsy (2010)

The axon initial segment (AIS) contains the site of action potential initiation and plays a major role in neuronal excitability. AIS function relies on high concentrations of different ion channels and complex regulatory mechanisms that orchestrate molecular microarchitecture. We review recent evidence that a large number of ion channels associated with epilepsy are enriched at the AIS, making it a 'hotspot' for epileptogenesis. Furthermore, we present novel data on the clustering of GABRgamma2 receptors in the AIS of cortical and hippocampal neurons in a knock in mouse model of a human genetic epilepsy. This article highlights the molecular coincidence of epilepsy mutations at the AIS and reviews pathogenic mechanisms converging at the AIS.
Generation of multivortex ring beams by inhomogeneous effective diffusion (2018)

By means of numerical simulations, we demonstrate generation of multivortex ring beams (MVRBs), i.e., circular chains built of small vortices, by launching necklace-shaped inputs, carrying angular momentum, into a dissipative optical medium modeled by the cubic-quintic complex Ginzburg–Landau equation with effective diffusion, which is periodically modulated in the longitudinal direction. The MVRB chains keep the original angular momentum. The number of external vortices is equal to the number of “beads” in the input necklace pattern. The individual small vortices are produced by the centrifugal force, which is originally induced by the angular momentum applied to the input necklace. Upon the propagation, the inner part of the MVRBs keeps initial counterclockwise direction of the rotation, while the outer part reverses to the clockwise direction (the present dissipative system does not conserve the angular momentum). Individual small vortices in the chain carry topological charge (“spin”) + 1, whose sign agrees with the clockwise rotation. MVRB states do not exist in the usual model with constant diffusion. The results offer a method to produce new kinds of vortex beams, which may find applications in optics.
Measurement of Tissue Interstitial Volume in Healthy Patients and Those with Amyloidosis with Equilibrium Contrast-enhanced MR Imaging (2013)

Equilibrium MR imaging can be used to define ECV within healthy tissues. ECV is increased in amyloidosis compared with healthy tissues, and this increase correlates with rising tissue amyloid burden.
ChemInform Abstract: NITROAZINES. 3. NITROACETONITRILE IN NITROAZINE SYNTHESIS (1985)

Abstract Die aus den Amino‐azolen durch Diazotierung hergestellten Diazoniumverbindungen (II) lassen sich in Gegenwart von Natriumacetat oder Natriumcarbonat mit Nitroacetonitril (III) zu Azolylhydrazonen (IV) des Nitroglyoxalsäurenitrils kondensieren.
Tooled: An Exploration of Craft, the Tool and Emergent Trends in Wooden Architecture (2018)

Thesis (Master's)--University of Washington, 2017