gebhart/patrepeval huggingface dataset:
Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1 with the EGF receptor. (1991)

Raf-1 serine- and threonine-specific protein kinase is transiently activated in cells expressing the epidermal growth factor (EGF) receptor upon treatment with EGF. The stimulated EGF receptor coimmunoprecipitates with Raf-1 kinase and mediates protein kinase C-independent phosphorylation of Raf-1 on serine residues. Hyperphosphorylated Raf-1 has lower mobility on sodium dodecyl sulfate gels and has sixfold-increased activity in immunocomplex kinase assay with histone H1 or Raf-1 sequence-derived peptide as a substrate. Raf-1 activation requires kinase-active EGF receptor; a point mutant lacking tyrosine kinase activity in inactive in Raf-1 coupling and association. It is noteworthy that tyrosine phosphorylation of c-Raf-1 induced by EGF was not detected in these cells. These observations suggest that Raf-1 kinase may act as an important downstream effector of EGF signal transduction.
Sirtuin-3 (SIRT3) and the Hallmarks of Cancer (2013)

Sirtuins (SIRT1-SIRT7), the mammalian homologs of the silent information regulator 2 (Sir2) in Saccharomyces cerevisiae, have been a major focus of study in the scientific community this past decade because of their emerging role in cancer biology and other age-related diseases. Emerging functions for this unique family of enzymes include roles in genomic stability, angiogenesis, metabolism, and anoikis. Here, we review recent developments on the role of sirtuins in cancer with a particular focus on SIRT3 and its role in the hallmarks of cancer and as a potential drug target for cancer treatment.
Designing a Dexterous Reconfigurable Packaging System for Flexible Automation (2003)

This paper presents a design for a reconfigurable packaging system that can handle cartons of different shape and sizes and is amenable to ever changing demands of packaging industries for perfumery and cosmetic products. The system takes structure of a multi-fingered robot hand, which can provide fine motions, and dexterous manipulation capability that may be required in a typical packaging-assembly line. The paper outlines advanced modeling and simulation undertaken to design the packaging system and discusses the experimental work carried out. The new packaging system is based on the principle of reconfigurability, that shows adaptability to simple as well as complex carton geometry. The rationale of developing such a system is presented with description of its human equivalent. The hardware and software implementations are also discussed together with directions for future research.
A comprehensive look at a new metrology technique to support the needs of lithography performance in near future (2008)

Need for accuracy, precision, speed and sophistication in metrology has increased tremendously over the past few years. Lithography performance will increasingly depend on post patterning metrology and this dependency will be heavily accelerated by technology shrinkage. These requirements will soon become so stringent that the current metrology capabilities may not be sufficient to support these near future needs. Accuracy and precision requirements approaching well into sub-nanometer range while the demand for increase in sampling also continues, triggering the need for a new technology in this area. In this technical presentation the authors would like to evaluate such technology that has the potential to support the future needs. Extensive data collection and tests are ongoing for both CD and overlay. Data on first order diffraction based overlay shows unprecedented measurement precision. The levels of precision are so low that for evaluation special methods has been developed and tested. In this paper overlay measurement method and data will be discussed, as well as applicability for future nodes and novel lithography techniques. CD data will be reported in the future technical publications.
Kinetics of Oxidized Cytosine Repair by Endonuclease III of Escherichia coli (1997)

Endonuclease III of Escherichia coli excises a broad range of oxidized, hydrated and ring-fragmented pyrimidines from DNA. The kinetic parameters were compared for repair of three potentially mutagenic oxidized cytosine lesions: 5,6-dihydroxy-5, 6-dihydro-2'-deoxyuridine (uracil glycol or Ug), 5-hydroxy-2'-deoxycytidine (5-ohC), and 5-hydroxy-2'-deoxyuridine (5-ohU). Site-specifically modified 40-mer oligonucleotides containing each of the three lesions in the same sequence context were synthesized chemically or by a combination of chemical and enzymatic methods. Appropriately protected phosphoramidites of 5-ohC and 5-ohU were synthesized and incorporated into oligonucleotides by standard solid-phase synthetic methods. The lability of Ug made it necessary to use an alternative approach to prepare the analogous 40-mers containing Ug. An uracil containing pentamer oligonucleotide was oxidized with OsO4 to generate the corresponding Ug containing product, which was then ligated into an oligonucleotide scaffold to generate 40 base pair duplexes. Using 32P-labeled substrates and a gel electrophoresis based assay, the values of Km and Vmax for excision of 5-ohC, 5-ohU, and Ug were determined. In this experimental system, the order of repair efficiency is Ug >> 5-ohC >> 5-ohU based on ratios of Vmax/Km. Modest effects were observed when the base paired opposite the lesion was changed from G to A.
Supplemental Figure 1 from Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit (2023)

&lt;p&gt;CONSORT diagram of patients included neoadjuvant targeted therapy trials&lt;/p&gt;
Reduction of Pump Pulsation Noise by Using Robust Design Method (2012)

In the past decade, high-pressure direct injection systems in petrol engines have widely penetrated in the market supported by the raising environmental consciousness. The essential component of a gasoline direct injection system is the high-pressure fuel pump, which pressurizes the petrol as high as 20MPa. High-pressure fuel pump commonly used is single-cylinder type driven mechanically by the cam-shaft. This typically generates inherent undesirable high pressure pulsation noise which renders the sound of the traditionally petrol engine similar to that of a common-rail diesel engine. In this paper, we will describe the method we deployed to mitigate the high pressure pulsation noise. We applied Taguchi methodology to search for the sensitive design parameters. As a result, by modifying design parameters of the outlet valve, we confirmed 48% reduction of pulsation noise.
Nitroxides Tempol and Tempo Induce Divergent Signal Transduction Pathways in MDA-MB 231 Breast Cancer Cells (1998)

Tempol and tempo are stable free radical nitroxides that possess antioxidant properties. In this study, we examined the effects of these compounds on components of the mitogen-activated protein kinase signal transduction cascade. Tempo treatment (15 min) of MDA-MB 231 human breast cancer cells resulted in significant levels of tyrosine phosphorylation of several as yet unidentified proteins compared with equimolar concentration of tempol (10 mM). Both compounds caused tyrosine phosphorylation and activation of Raf-1 protein kinase (30 min, 2-3-fold). Interestingly, however, only tempol caused increased extracellular signal-regulated kinase 1 activity (2 h, approximately 3-fold). On the other hand, tempo, but not tempol, potently activated stress-activated protein kinase (2 h, >3-fold). Consistent with these data, tempol was found to be noncytotoxic, whereas tempo induced apoptotic cell death (2 h, >50%). Tempo treatment also resulted in significant elevation of ceramide levels at 30 min (54% over control) and 1 h (71% over control) posttreatment, preceding stress-activated protein kinase activation and apoptosis. These data suggest that in the absence of an environmental oxidative stress, tempol and tempo elicit distinct cellular signaling pathways. The recognition of the molecular mechanisms of nitroxide action may have important implications for biological effectiveness of these compounds.
Characterization of guided resonances in photonic crystal slabs using terahertz time-domain spectroscopy (2006)

We describe experimental studies of guided resonances in two-dimensional photonic crystal slabs using coherent single-cycle terahertz pulses. Our measurements directly reveal two stages of pulse transmission in the time domain: an initial pulse resulting from the direct transmission through the photonic crystal slab and a long-lived decaying tail resulting from the finite lifetime of guided resonance modes. These reflect the coupling of a set of discrete modes to the free-space continuum, which produces guided resonances with Fano resonance profiles. Phase spectra are also obtained experimentally, and these also exhibit the signatures of guided resonances. By changing the incident angle of the input beam, we change the spectrum of guided resonances excited by the incident wave. Our experimental results are in good agreement with numerical simulations.
Injectable polymer-nanoparticle hydrogel for the sustained intravitreal delivery of bimatoprost (2022)

Abstract Vision impairment resulting from chronic eye diseases, such as macular degeneration and glaucoma, severely impacts patients’ quality of life and poses an immense global financial burden. Current standard of care for such diseases includes daily eye drops or frequent intravitreal (ITV) injections, which are burdensome treatment modalities resulting in low patient compliance. There remains a growing need for easily administered long-acting delivery technologies for prolonging exposure of ocular therapeutics with each administration. Here, we deploy a supramolecular polymer-nanoparticle (PNP) hydrogel for ITV delivery of the glaucoma drug bimatoprost. PNP hydrogels are shear-thinning and self-healing, key properties for injectability, and enable slow release of molecular cargo in vitreous humor (VH) mimics. An in vivo study in New Zealand white rabbits demonstrated intravitreally injected PNP hydrogels form depots that degrade slowly over time, maintaining detectable levels of bimatoprost in the VH up to eight weeks following injection. Ophthalmic examinations and histopathology identified a mild foreign body response (FBR) to the hydrogel, characterized by rare clusters of foamy macrophages and giant cells associated with minimal, patchy fibroplasia. This work shows that PNP hydrogels exhibit numerous desirable traits for sustained drug delivery and further work will be necessary to optimize tolerability in the eye.
Detecting EEG evoked responses for target image search with mixed effect models (2008)

There is evidence that brain signals associated with perceptual processes can be used for target image search. We describe the application of mixed effect models (MEMs) to brain signature detection. We develop an MEM detector for detecting brain evoked responses generated by perceptual processes in the human brain associated with detecting novel target stimuli. We construct the model using principal component analysis and linear discriminant analysis (LDA) bases. We adopt the LDA for dimension reduction. For parameter regularization we use 10-fold cross validation and report experimental results from six subjects. Four out of six subjects achieve very good detection performance with more than 0.9 areas under receiver operating characteristic curves. The results demonstrate that the MEM can provide reliable inference on single-trial ERP detection on the task of target image search.
An Experience of Multiple Hematomas in a Coronavirus Disease-19 Patient Administered with ART-123 and Heparin (2021)

Our findings show that anticoagulation therapy and a history of falls induced multiple hematomas in a COVID-19 patient and that the condition was managed with TAE. When anticoagulants are considered in the management of Af and COVID-19 associated coagulopathy, it is necessary to closely monitor potential bleeding complications.
Colloidal Assembling Template with Wrinkled Patterns Based on Liquid Crystalline Polymer (2015)

Colloidal microwires are constructed using anisotropic assembling templates with periodically wrinkled patterns of a liquid crystalline polymer (LCP). The wrinkled LCP patterns with the period of a few micrometers are produced from reactive mesogens on an alignment layer by the oxygen plasma treatment and used for assembling colloidal particles into microwires through a simple slit-coating process. A two-directional assembly of the colloidal particles is also demonstrated on the LCP template with two stamping-assisted rubbing directions. Our approach to the colloidal assembly is applicable for building up advanced photonic and optoelectronic devices.
High diversity of the immune repertoire in humanized NOD.SCID.γc−/− mice (2009)

The diversity of the human immune repertoire and how it relates to a functional immune response has not yet been studied in detail in humanized NOD.SCID.gammac(-/-) immunodeficient mice. Here, we used a multiplex PCR on genomic DNA to quantify the combinatorial diversity of all possible V-J rearrangements at the TCR-beta chain and heavy chain Ig locus. We first show that the combinatorial diversity of the TCR-beta chain generated in the thymus was well preserved in the periphery, suggesting that human T cells were not vastly activated in mice, in agreement with phenotypic studies. We then show that the combinatorial diversity in NOD.SCID.gammac(-/-) mice reached 100% of human reference samples for both the TCR and the heavy chain of Ig. To document the functionality of this repertoire, we show that a detectable but weak HLA-restricted cellular immune response could be elicited in reconstituted mice after immunization with an adenoviral vector expressing HCV envelope glycoproteins. Altogether, our results suggest that humanized mice express a diversified repertoire and are able to mount antigen-specific immune responses.
Large-scale calcium imaging with a head-mounted axial scanning 3D fluorescence microscope (2021)

Summary Miniaturized fluorescence microscopes are becoming more important for deciphering the neural codes underlying various brain functions. With gradient index (GRIN) lenses, these devices enable recording neuronal activity in deep brain structures. However, to minimize any damage to brain tissues and local circuits, the diameter of the GRIN lens should be 0.5–1 mm, resulting in a small field of view. Volumetric imaging capability might increase the number of neurons imaged through the lenses considering the three-dimensional (3D) structure of neural circuits in the brain. To observe 3D calcium dynamics, we developed a miniaturized microscope with an electrically tunable lens and a novel CNMF-based neural signal extraction algorithm for wide-field 3D imaging data. By combining the hardware and software, approximately 1000 neurons were imaged from the cortices of freely behaving mice. Compared with the state-of-the-art 2D imaging technique, the proposed 3D method imaged 1.7–2.6 times more cells with a higher separation of cellular signals.
Laser terahertz-emission microscope for inspecting electrical faults in integrated circuits (2003)

A laser terahertz-emission microscope (LTEM) system is proposed and developed for inspecting electrical faults in integrated circuits (IC). We test a commercial operational amplifier while the system is operating. Two-dimensional terahertz-emission images of the IC chip are clearly observed while the chip is scanned with a femtosecond laser. When one of the interconnection lines is cut, the damaged chip has a LTEM image different from that of normal chips. The results indicate that the LTEM system is a potential tool for IC inspection.
Control of Resistant Pink Bollworm ( Pectinophora gossypiella ) by Transgenic Cotton That Produces Bacillus thuringiensis Toxin Cry2Ab (2002)

Crops genetically engineered to produce Bacillus thuringiensis toxins for insect control can reduce use of conventional insecticides, but insect resistance could limit the success of this technology. The first generation of transgenic cotton with B. thuringiensis produces a single toxin, Cry1Ac, that is highly effective against susceptible larvae of pink bollworm (Pectinophora gossypiella), a major cotton pest. To counter potential problems with resistance, second-generation transgenic cotton that produces B. thuringiensis toxin Cry2Ab alone or in combination with Cry1Ac has been developed. In greenhouse bioassays, a pink bollworm strain selected in the laboratory for resistance to Cry1Ac survived equally well on transgenic cotton with Cry1Ac and on cotton without Cry1Ac. In contrast, Cry1Ac-resistant pink bollworm had little or no survival on second-generation transgenic cotton with Cry2Ab alone or with Cry1Ac plus Cry2Ab. Artificial diet bioassays showed that resistance to Cry1Ac did not confer strong cross-resistance to Cry2Aa. Strains with >90% larval survival on diet with 10 microg of Cry1Ac per ml showed 0% survival on diet with 3.2 or 10 microg of Cry2Aa per ml. However, the average survival of larvae fed a diet with 1 microg of Cry2Aa per ml was higher for Cry1Ac-resistant strains (2 to 10%) than for susceptible strains (0%). If plants with Cry1Ac plus Cry2Ab are deployed while genes that confer resistance to each of these toxins are rare, and if the inheritance of resistance to both toxins is recessive, the efficacy of transgenic cotton might be greatly extended.
A Multi-Site Validation of Human Aβ42 and Human Total Tau Assays for Use in Human CSF (IN3-1.009) (2013)

OBJECTIVE: To conduct an external validation of MSD's Human Aβ42 and Human Total Tau Kits by nine independent testing sites, including academic institutions, biopharmaceutical institutions, and CROs.
A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology (2010)

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology.
evaluation of argon laser photocoagulation in a series of animal models of upper gastrointestinal bleeding (1980)

During the past five years we have evaluated argon laser photocoagulation in various canine models of upper gastrointestinal hemorrhage. In gastric erosions, the eight-watt argon laser was uniformly effective in stopping bleeding. In our standard acute ulcer model the seven-watt argon laser was effective in stopping bleeding from most ulcers and only occasionally produced deep injury. With the addition of a jet of CO2 exiting the laser catheter coaxial to the laser beam, the argon laser was 100% effective and no deep injury resulted. The application of the argon laser in a more physiologic canine bleeding model using a single bleeding vessel in an ulcer base is currently under study. The development of improved animal models of gastrointestinal bleeding should contribute to the identification of effective and safe endoscopic hemostatic methods.
Das periodische System von Primo Levi – eine Suche nach Strukturen in der Vergangenheit (2004)

Den Zauber der chemischen Elemente entfaltet Primo Levi in seinem autobiographischen Meisterwerk Das periodische System , das sich, wie alle Kunstwerke, die die Zeit überdauern, vielschichtiger Interpretation öffnet. Ein Vierteljahrhundert nach seinem Erscheinen lohnt sich ein erneuter Blick auf das Werk.
Characteristic Structures of Ce-Based Amorphous Heavy Fermion Systems (1995)

X-ray diffractions are measured for Ce–Cu, Ce–Ru and Ce–Si amorphous alloys produced by DC triode sputtering. The radial distribution functions, RDF’s, are derived from these measurements and compared with RDF of the intermetallics with nearly the same compositions as those of the amorphous alloys. The short range structures of the Ce–Cu and Ce–Si amorphous alloys are chemically ordered ones in the nearest neighbor ranges, resembling their crystalline counterparts. The short range structures of the Ce–Ru amorphous alloys, on the other hand, are disordered ones, being different from those of their crystalline counterpart. The structure characteristics are discussed with their low temperature physical properties similar and dissimilar to those of the crystalline counterparts.
The connectivity sonar (2003)

Web sites today serve many different functions, such as corporate sites, search engines, e-stores, and so forth. As sites are created for different purposes, their structure and connectivity characteristics vary. However, this research argues that sites of similar role exhibit similar structural patterns, as the functionality of a site naturally induces a typical hyperlinked structure and typical connectivity patterns to and from the rest of the Web. Thus, the functionality of Web sites is reflected in a set of structural and connectivity-based features that form a typical signature. In this paper, we automatically categorize sites into eight distinct functional classes, and highlight several search-engine related applications that could make immediate use of such technology. We purposely limit our categorization algorithms by tapping connectivity and structural data alone, making no use of any content analysis whatsoever. When applying two classification algorithms to a set of 202 sites of the eight defined functional categories, the algorithms correctly classified between 54.5% and 59% of the sites. On some categories, the precision of the classification exceeded 85%. An additional result of this work indicates that the structural signature can be used to detect spam rings and mirror sites, by clustering sites with almost identical signatures.
Inhibition of melanoma development in the Nras(Q61K)::Ink4a−/− mouse model by the small molecule BI‐69A11 (2012)

To date, there are no effective therapies for tumors bearing NRAS mutations, which are present in 15-20% of human melanomas. Here we extend our earlier studies where we demonstrated that the small molecule BI-69A11 inhibits the growth of melanoma cell lines. Gene expression analysis revealed the induction of interferon- and cell death-related genes that were associated with responsiveness of melanoma cell lines to BI-69A11. Strikingly, the administration of BI-69A11 inhibited melanoma development in genetically modified mice bearing an inducible form of activated Nras and a deletion of the Ink4a gene (Nras((Q61K)) ::Ink4a(-/-) ). Biweekly administration of BI-69A11 starting at 10 weeks or as late as 24 weeks after the induction of mutant Nras expression inhibited melanoma development (100 and 36%, respectively). BI-69A11 treatment did not inhibit the development of histiocytic sarcomas, which constitute about 50% of the tumors in this model. BI-69A11-resistant Nras((Q61K)) ::Ink4a(-/-) tumors exhibited increased CD45 expression, reflective of immune cell infiltration and upregulation of gene networks associated with the cytoskeleton, DNA damage response, and small molecule transport. The ability to attenuate the development of NRAS mutant melanomas supports further development of BI-69A11 for clinical assessment.