gebhart/patrepeval huggingface dataset:
Abstract 4493: Medi-573 alone or in combination with mammalian target of rapamycin inhibitors, targets the insulin-like growth factor pathway in sarcomas (2014)

Abstract MEDI-573 is a human antibody that neutralizes the insulin-like growth factors, IGF-1 and IGF-2. IGFs are over-expressed in multiple types of cancer; their over-expression is a potential mechanism for resistance to IGF-1 receptor (IGF-1R)-targeting therapy. Effects of IGFs on cell proliferation, differentiation, and survival are mediated through their binding to and activation of IGF-1R or insulin receptor A (IR-A). In this study, we studied the anti-tumor activity and mechanism of action of MEDI-573 in models of sarcoma. MEDI-573 potently inhibited in vitro proliferation of several sarcoma cell lines, with Ewing's sarcoma cell lines being the most sensitive. This inhibition also occurred after growth stimulation with added IGF-1- and IGF-2. The effect of MEDI-573 on IGF signaling was also examined. Treatment with MEDI-573 markedly reduced levels of pIGF-1R, pIR, and pAKT, and significantly blocked IGF-1- and IGF-2-induced activation of the IGF-1R and AKT pathways. MEDI-573 inhibited the growth of sarcoma xenografts in vivo, and inhibition correlated with neutralization of IGF-1 and IGF-2. Combination of MEDI-573 with either rapamycin or another mTOR inhibitor, AZD2014, significantly enhanced the anti-tumor activity of MEDI-573, and this response correlated with modulation of AKT and mTOR signaling. In summary, sarcoma cells respond to autocrine or paracrine growth stimulation by secreted IGF-1 and IGF-2, and inhibition of IGF-1 and IGF-2 by MEDI-573 results in potent anti-tumor activity in several sarcoma models. Our data provide evidence for evaluation of MEDI-573 and mTORi combinations in clinical studies of sarcoma patients. Note: This abstract was not presented at the meeting. Citation Format: Haihong Zhong, Christine Fazenbaker, Shannon Breen, Cui Chen, Jiaqi Huang, Morehouse Chris, Yihong Yao, Robert Hollingsworth. Medi-573 alone or in combination with mammalian target of rapamycin inhibitors, targets the insulin-like growth factor pathway in sarcomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4493. doi:10.1158/1538-7445.AM2014-4493
Light emission from metal-insulator-metal structures biased near breakdown voltages (1986)

Optical emission is observed at prebreakdown voltages in thin film metal-insulator-metal (MIM) structures. Subsequent examination of the junction in a scanning electron microscope (SEM) reveals filamentary growth through the insulator. These tunnel junctions consist of Al-Al/sub 2/O/sub 3/-Ag or Al-Al/sub 2/O/sub 3/-Au with a variety of microstructures incorporated in the junction. The emission spectrum is found to be dependent on the geometry of the MIM structure. Comparison of theory and experiment suggests the emission results from the radiative decay of collective electronic excitations (surface plasmons) initiated by electrons tunneling through the insulator.
The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation (1998)

The spindle assembly checkpoint mechanism delays anaphase initiation until all chromosomes are aligned at the metaphase plate. Activation of the anaphase-promoting complex (APC) by binding of CDC20 and CDH1 is required for exit from mitosis, and APC has been implicated as a target for the checkpoint intervention. We show that the human checkpoint protein hMAD2 prevents activation of APC by forming a hMAD2-CDC20-APC complex. When injected into Xenopus embryos, hMAD2 arrests cells at mitosis with an inactive APC. The recombinant hMAD2 protein exists in two-folded states: a tetramer and a monomer. Both the tetramer and the monomer bind to CDC20, but only the tetramer inhibits activation of APC and blocks cell cycle progression. Thus, hMAD2 binding is not sufficient for inhibition, and a change in hMAD2 structure may play a role in transducing the checkpoint signal. There are at least three different forms of mitotic APC that can be detected in vivo: an inactive hMAD2-CDC20-APC ternary complex present at metaphase, a CDC20-APC binary complex active in degrading specific substrates at anaphase, and a CDH1-APC complex active later in mitosis and in G1. We conclude that the checkpoint-mediated cell cycle arrest involves hMAD2 receiving an upstream signal to inhibit activation of APC.
Amount of Stationary Phase--Time Normalization Chromatography (1971)

Journal Article Amount of Stationary Phase—Time Normalization Chromatography Get access Eli Grushka, Eli Grushka Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Yepes-Baraya, M. Yepes-Baraya Department of Chemistry, State University of New York at Buffalo, Buffalo, New York 14214 Search for other works by this author on: Oxford Academic PubMed Google Scholar W. D. Cooke W. D. Cooke Department of Chemistry, Cornell University, Ithaca, New York 14850 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Chromatographic Science, Volume 9, Issue 11, November 1971, Pages 653–664, https://doi.org/10.1093/chromsci/9.11.653 Published: 01 November 1971 Article history Received: 22 June 1971 Published: 01 November 1971
Rewritable DNA Microarrays (2006)

Thiol-terminated single-stranded deoxyribonucleic acids (ssDNA) can be immobilized onto pulsed plasma deposited poly(allylmercaptan) surfaces via disulfide bridge chemistry and are found to readily undergo nucleic acid hybridization. Unlike other methods for oligonucleotide attachment to solid surfaces, this approach is shown to be independent of substrate material or geometry, and amenable to highly efficient rewriting.
Expression of a kinase anchor protein 75 depletes type II cAMP-dependent protein kinases from the cytoplasm and sequesters the kinases in a particulate pool. (1993)

A kinase anchor proteins (AKAPs) have a C-terminal binding site for the regulatory subunit (RII beta) of cAMP-dependent protein kinase II beta (PKAII beta) and an N-terminal domain that mediates the targeting and attachment of the anchor protein to intracellular structures. In vitro biochemical studies and recent in situ immunocytochemical analysis (Glantz, S. B., Amat, J. A., and Rubin, C. S. (1992) Mol. Biol. Cell 3, 1215-1228) suggest that AKAPs anchor PKAII beta at specific sites in the dendritic cytoskeleton of neurons. This arrangement would place PKAII beta in proximity with its substrates and create "target sites" for cAMP actions. The foregoing model predicts that (a) RII subunits are freely accessible to AKAPs, (b) PKAII holoenzymes, as well as RII subunits, are anchored, and (c) changes in the level of AKAP can alter the intracellular distribution of type II PKAs. We have addressed these previously untested propositions by overexpressing bovine AKAP75 in a human cell line (HEK293). Non-transfected cells express a low level of endogenous AKAP79, and approximately 90% of RII alpha and RII beta subunits are isolated in the cell cytosol. In contrast, stably transfected cells, which express a 10-fold excess of AKAP75, sequester > 90% of their RII subunits in a particulate pool. Catalytic subunits are also transferred to this pool. AKAP75 accumulates in a cell compartment with biochemical properties characteristic of cytoskeleton. Thus, AKAPs have access to and avidly bind cytoplasmic type II PKAs. Moreover, an increase in AKAP content can alter the particulate/cytoplasmic distribution of PKAII beta and PKAII alpha.
Alpha-Synuclein defects autophagy by impairing SNAP29-mediated autophagosome-lysosome fusion (2021)

Dopaminergic (DA) cell death in Parkinson's disease (PD) is associated with the gradual appearance of neuronal protein aggregates termed Lewy bodies (LBs) that are comprised of vesicular membrane structures and dysmorphic organelles in conjunction with the protein alpha-Synuclein (α-Syn). Although the exact mechanism of neuronal aggregate formation and death remains elusive, recent research suggests α-Syn-mediated alterations in the lysosomal degradation of aggregated proteins and organelles - a process termed autophagy. Here, we used a combination of molecular biology and immunochemistry to investigate the effect of α-Syn on autophagy turnover in cultured human DA neurons and in human post-mortem brain tissue. We found α-Syn overexpression to reduce autophagy turnover by compromising the fusion of autophagosomes with lysosomes, thus leading to a decrease in the formation of autolysosomes. In accord with a compensatory increase in the plasma membrane fusion of autophagosomes, α-Syn enhanced the number of extracellular vesicles (EV) and the abundance of autophagy-associated proteins in these EVs. Mechanistically, α-Syn decreased the abundance of the v-SNARE protein SNAP29, a member of the SNARE complex mediating autophagolysosome fusion. In line, SNAP29 knockdown mimicked the effect of α-Syn on autophagy whereas SNAP29 co-expression reversed the α-Syn-induced changes on autophagy turnover and EV release and ameliorated DA neuronal cell death. In accord with our results from cultured neurons, we found a stage-dependent reduction of SNAP29 in SNc DA neurons from human post-mortem brain tissue of Lewy body pathology (LBP) cases. In summary, our results thus demonstrate a previously unknown effect of α-Syn on intracellular autophagy-associated SNARE proteins and, as a consequence, a reduced autolysosome fusion. As such, our findings will therefore support the investigation of autophagy-associated pathological changes in PD.
Quantization of angle - variables (1993)

Quantization of angle-variables in the classical Hamilton mechanics with one degree of freedom is considered in a mathematically rigorous way. The method taken in this paper is that of the Weyl quantization, so that the quantized angles are given by pseudo-differential operators of the Weyl type which may be singular. Some operator-theoretical aspects of the quantized angles are discussed. It is shown that the relation between a classical Hamiltonian and an angle-variable of it, which is given by a Poisson bracket relation, is not preserved in general to the quantized version where the Poisson bracket relation is replaced by a commutation relation; an "anomaly" may occur in the commutation relation of the quantized Hamiltonian with the quantized angle. The anomaly may be regarded as a quantum effect. Special attention is paid to the case of the harmonic oscillator. It is proven that the quantized angle eh of the harmonic oscillator, where 1i &gt; 0 is a parameter denoting the Planck constant divided by 211", is represented as an integral operator of the Carleman type. The integral operator representation enables one to expand eh as a power series of n-1, which describes the aymptotic behavior of eh as 1i -+ oo. Also it is shown that the classical limit 1i-+ 0 of eh is given by a modified Hilbert transform.
On the Role of Task Design in Crowdsourcing Campaigns (2015)

Despite the success of crowdsourcing marketplaces, fully harnessing their massive workforce remains challenging. In this work we study the effect on crowdsourcing campaigns of different feedback and payment strategies. Our results reveal the joint effect of feedback and payment on the quality and quantity of the outcome.
Safer and Sustainable-by-Design Hydroxyapatite Nanobiomaterials for Biomedical Applications: Assessment of Environmental Hazards (2022)

Developments in the nanotechnology area occur ensuring compliance with regulatory requirements, not only in terms of safety requirements, but also to meet sustainability goals. Hence, safer and sustainable-by-design (SSbD) materials are also aimed for during developmental process. Similar to with any new materials their safety must be assessed. Nanobiomaterials can offer large advantages in the biomedical field, in areas such as tissue repair and regeneration, cancer therapy, etc. For example, although hydroxyapatite-based nanomaterials (nHA) are among the most studied biomaterials, its ecotoxicological effects are mostly unknown. In the present study we investigated the toxicity of seven nHA-based materials, covering both different biomedical applications, e.g., iron-doped hydroxyapatite designed for theragnostic applications), hybrid collagen/hydroxyapatite composites, designed for bone tissue regeneration, and SSbD alternative materials such as titanium-doped hydroxyapatite/alginate composite, designed as sunscreen. The effects were assessed using the soil model <i>Enchytraeus crypticus</i> (Oligochaeta) in the natural standard LUFA 2.2 soil. The assessed endpoints included the 2, 3 and 4 days avoidance behavior (short-term), 28 days survival, size and reproduction (long term based on the OECD standard reproduction test), and 56 days survival and reproduction (longer-term OECD extension). Although overall results showed little to no toxicity among the tested nHA, there was a significant decrease in animals' size for Ti-containing nHA. Moreover, there was a tendency for higher toxicity at the lowest concentrations (i.e., 100 mg/kg). This requires further investigation to ensure safety.
Estimation of right ventricular volume, quantitative assessment of wall motion and trabeculae mass in arrhythmogenic right ventricular dysplasia (2010)

The aim of this study was to gain a wide perspective of the arrhythmogenic right ventricular dysplasia (ARVD) by developing algorithms for Cardiac Magnetic Resonance Imaging. We developed a semi-automatic procedure to assess the Right Ventricle (RV) volumes and to quantify RV wall motion; moreover, with the increased visible details in a single MR image, a manual method to evaluate the trabeculae mass was performed. All the algorithms used were based on the level set theory which allows detecting both endocardial and wall surfaces, as well as the black parts characterizing the trabeculae. 6 normal subjects and 6 subjects with ARVD heve been investigated. Our method and the standard manual method for volume estimation were significantly correlated (y=0.92x+6.56), (r=0.92 p&lt;0.001). Wall Motion results showed a significant reduction of RV segmental function in patients with ARVD, Inferior Wall was the most involved with more than 80% reduction (p&lt;0.001) compared with normal subjects, while RV outflow tract (RVOT) was the least involved with less than 50% reduction (p&lt;0.001) compared to normal subjects. A repeatability test was executed on trabeculae mass assessment, which showed a high intra observer correlation, in fact the results were significant at 95% of the cases.
A Mouse Diversity Panel Approach Reveals the Potential for Clinical Kidney Injury Due to DB289 Not Predicted by Classical Rodent Models (2012)

DB289 is the first oral drug shown in clinical trials to have efficacy in treating African trypanosomiasis (African sleeping sickness). Mild liver toxicity was noted but was not treatment limiting. However, development of DB289 was terminated when several treated subjects developed severe kidney injury, a liability not predicted from preclinical testing. We tested the hypothesis that the kidney safety liability of DB289 would be detected in a mouse diversity panel (MDP) comprised of 34 genetically diverse inbred mouse strains. MDP mice received 10 days of oral treatment with DB289 or vehicle and classical renal biomarkers blood urea nitrogen (BUN) and serum creatinine (sCr), as well as urine biomarkers of kidney injury were measured. While BUN and sCr remained within reference ranges, marked elevations were observed for kidney injury molecule-1 (KIM-1) in the urine of sensitive mouse strains. KIM-1 elevations were not always coincident with elevations in alanine aminotransferase (ALT), suggesting that renal injury was not linked to hepatic injury. Genome-wide association analyses of KIM-1 elevations indicated that genes participating in cholesterol and lipid biosynthesis and transport, oxidative stress, and cytokine release may play a role in DB289 renal injury. Taken together, the data resulting from this study highlight the utility of using an MDP to predict clinically relevant toxicities, to identify relevant toxicity biomarkers that may translate into the clinic, and to identify potential mechanisms underlying toxicities. In addition, the sensitive mouse strains identified in this study may be useful in screening next-in-class compounds for renal injury.
Boosting computational creativity with human interaction in mixed-initiative co-creation tasks (2016)

Research in computational creativity often focuses on autonomously creative systems, which incorporate creative processes and result in creative outcomes. However, the integration of artificially intelligent processes in human-computer interaction tools necessitates that we identify how computational creativity can be shaped and ultimately enhanced by human intervention. This paper attempts to connect mixed-initiative design with established theories of computational creativity, and adapt the latter to accommodate a human initiative impacting computationally creative processes and outcomes. Several case studies of mixed-initiative tools for design and play are used to corroborate the arguments in this paper.
Peroxides of elements other than carbon. Part XI. The autoxidation of some trialkylboroxines (1966)

Trialkylboroxines in solution react with oxygen to give organoperoxyboron compounds. Tri-t-butylboroxine gives tri-t-butylperoxyboroxine in good yield. With tri-s-butylboroxine the reaction proceeds to about 80% completion, and with tri-n-butylboroxine a maximum of only about two thirds of the theoretical amount of oxygen is absorbed. The mechanism of the oxidation is discussed, and it is pointed out that the evidence does not exclude the possibility of a free-radical process.
Competitiveness and Management of Technology (2015)

This paper delves into competition and technology management as a means of economic development. Expanding from Porter's framework on competitiveness and using a novel framework of PTGE（People, Technology, Government and Environment）, this paper argues that three types of competitive advantage could be created. These competitive advantages range from passive to active advantages, i.e. natural advantage, duplicated advantage and niche advantage. Technology and effective management of technology become the key differentiating factors in determining one's competitiveness. This paper discusses key aspects of technology management, namely R&D management, new product development and technology strategy in enhancing competitiveness that may lead to the creation of one of the competitive advantage mentioned.
Chemoenzymatisch-chemische Synthese eines (2-3)-Sialyl-T-Threonin-Bausteins und dessen Einsatz in der Synthese der N-terminalen Sequenz von Leukämie-assoziiertem Leukosialin (CD43) (2001)

Durch Schutz aller funktionellen Gruppen im Kohlenhydratteil des chemoenzymatisch hergestellten Sialyl-T-Threoninesters 1 (R=R1=H, R2=tBu; Fmoc=9-Fluorenylmethoxycarbonyl) erhielt man einen für die chemische Synthese geeigneten Baustein 2 (R=Ac, R1=Me, R2=H), der zur Festphasensynthese der N-terminalen Sequenz 3 des Leukämie-assoziierten Leukosialins eingesetzt wurde.
Cover Feature: Extended Limits of Reversible Electrochemical Lithiation of Crystalline V2O5 (ChemElectroChem 7/2019) (2019)

The Cover Feature shows the intercalation of lithium ions into vanadium oxide covered with reduced graphene oxide. Uniform electron transport in such material extends the limits of V2O5 reversible electrochemical lithiation. More information can be found in the Article by D. M. Itkis et al. on page 2013 in Issue 7, 2019 (DOI: 10.1002/celc.201801638).
Spatial diversity two-branch antenna for wireless devices (2006)

A two-branch diversity antenna using a simple printed dual band double-T monopole and operating at 2.4 and 5.2 GHz in the ISM band is presented. A prototype of the proposed antenna has been constructed and tested. The measured results are in good agreement with the computed ones from simulation, while the antenna has favourable characteristics such as reduced size and extended bandwidth.
Biological Factors behind Melanoma Response to Immune Checkpoint Inhibitors (2020)

Modern immunotherapy together with targeted therapy has revolutionized the treatment of advanced melanoma. Inhibition of immune checkpoints significantly improved the median overall survival and gave hope to many melanoma patients. However, this treatment has three serious drawbacks: high cost, serious side effects, and an effectiveness limited only to approximately 50% of patients. Some patients do not derive any or short-term benefit from this treatment due to primary or secondary resistance. The response to immunotherapy depends on many factors that fall into three main categories: those associated with melanoma cells, those linked to a tumor and its microenvironment, and those classified as individual ontogenic and physiological features of the patient. The first category comprises expression of PD-L1 and HLA proteins on melanoma cells as well as genetic/genomic metrics such as mutational load, (de)activation of specific signaling pathways and epigenetic factors. The second category is the inflammatory status of the tumor: "hot" versus "cold" (i.e., high versus low infiltration of immune cells). The third category comprises metabolome and single nucleotide polymorphisms of specific genes. Here we present up-to-date data on those biological factors influencing melanoma response to immunotherapy with a special focus on signaling pathways regulating the complex process of anti-tumor immune response. We also discuss their potential predictive capacity.
IZOD IMPACT MACHINE FOR A WIDE RANGE OF SINGLE AND REPEATED IMPACT TESTS (1970)

A pneumatically operated lifting mechanism and a fluidic control system have been added to an Izod impact testing machine for automatic repetition and counting of impacts from an adjustable preset striking height of the pendulum hammer and for automatic stopping of the machine on failure of the specimen.
X-Ray Study on Stellar/Intermediate Mass Black Holes (2007)

Based on early &lt;it&gt;Suzaku&lt;/it&gt; observations, properties of stellar-mass black-hole binaries (BHBs) and ultra-luminous compact X-ray sources (ULXs) are discussed. A comparison between GRO 1655-40 and Cygnus X-1, both observed in the Low/Hard state, gives new constraints on the characteristics of hot Compton cloud that are considered to be responsible for the formation of the Low/Hard state continua. Hard X-rays, with energies above 10 keV, were detected for the first time from a ULX, namely M82 X-1. Including this case, ULXs showing power-law like spectra are considered to host Comptonized accretion disks, in analogy to BHBs in the Very High state. In contrast, ULXs exhibiting multicolor-disk type spectra are interpreted to harbor “slim” disks. This sort of analogy between ULXs and BHBs suggests that black holes in ULXs are significantly more massive than those in BHBs.
A 48-dB DR 80-MHz BW 8.88-GS/s bandpass ΔΣ ADC for RF digitization with integrated PLL and polyphase decimation filter in 40nm CMOS (2011)

A 2.22GHz 4th-order BP ΔΣ ADC has been realized in 40nm CMOS. The test chip contains a complete system consisting of the ADC core, the PLL with clock generation network, and the digital decimation filters and downconversion (DFD). The quantizers are 6 times interleaved enabling a polyphase structure for the DFD and relaxing speed requirements. Sampled at 8.88GS/s the ADC achieves a DR of 48dB in a band of 80MHz with an IIP3 of +1dBm.