gebhart/patrepeval huggingface dataset:
Three-dimensional integrated optics using polymers (1999)

Some of the key components are demonstrated to make three-dimensional (3-D) optical integrated circuits possible using polymers. Fabrication techniques of shadow reactive ion etching, shadow photolithography, and gray-level photolithography to produce complex 3-D integrated optic structures are demonstrated. Vertical waveguide bends exhibit excess losses of <0.3 dB, and vertical power splitters possess predictable output splitting ratios between multiple core levels with excess losses of <0.5 dB. Vertical polarization splitters exhibit power extinction ratios of 15 dB between the output core layers. A 1/spl times/4 vertical-horizontal power splitter is also demonstrated. Additionally, these techniques are used to integrate different polymer materials into the same optical circuit while easily solving the mode mismatch problem. To show the technique, a polymer electrooptic modulator is vertically integrated with a low-loss waveguide.
Point Mutations Identified in Lec8 Chinese Hamster Ovary Glycosylation Mutants That Inactivate Both the UDP-galactose and CMP-sialic Acid Transporters (2001)

Nucleotide-sugar transporters (NSTs) are critical components of glycosylation pathways in eukaryotes. The identification of structural elements that are involved in NST functions provides an important task. Chinese hamster ovary glycosylation mutants defective in nucleotide-sugar transport provide access to inactive transporters that can define such structure/function relationships. In this study, we have cloned the hamster UDP-galactose transporter (UGT) and identified defects in UGT gene transcripts from nine independent Chinese hamster ovary mutants that belong to the Lec8 complementation group. Reverse transcription polymerase chain reaction with primers that span the UGT open reading frame showed that three Lec8 mutants express a full-length open reading frame, while six Lec8 mutants predominantly express truncated UGT gene transcripts. Sequencing identified different single or triplet nucleotide changes in full-length UGT transcripts from three of the mutants. These mutations translate into three different amino acid changes at positions that are highly conserved in all the known mammalian NSTs. Transfection of a cDNA encoding either of the mutations Delta serine 213 or G281D failed to correct the UDP-galactose transport defect in Lec8 transfectants. Most importantly, introducing these same mutations into the homologous region of the murine CMP-sialic acid transporter caused inactivation of this transporter. Thus, identifying point mutations that inactivate UGT in Lec8 mutants resulted in the discovery of amino acids that are critical to the activity of both UGT and CST, the two most divergent mammalian NSTs.
New Type III Effectors from Xanthomonas campestris pv. vesicatoria Trigger Plant Reactions Dependent on a Conserved N-Myristoylation Motif (2007)

Pathogenicity of the gram-negative plant pathogen Xanthomonas campestris pv. vesicatoria depends on a type III secretion system, which translocates bacterial effector proteins into the plant cell. In this study, we identified two novel type III effectors, XopE1 and XopE2 (Xanthomonas outer proteins), using the AvrBs3 effector domain as reporter. XopE1 and XopE2 belong to the HopX family and possess a conserved putative N-myristoylation motif that is also present in the effector XopJ from X. campestris pv. vesicatoria 85-10. XopJ is a member of the YopJ/AvrRxv family of acetyltransferases. Confocal laser scanning microscopy and immunocytochemistry revealed that green fluorescent protein fusions of XopE1, XopE2, and XopJ localized to the plant cell plasma membrane. Targeting to the membrane is probably due to N-myristoylation, because a point mutation in the putative myristoylated glycine residue G2 in XopE1, XopE2, and XopJ resulted in cytoplasmic localization of the mutant proteins. Results of hydroxylamine treatments of XopE2 protein extracts suggest that the proteins are additionally anchored in the host cell plasma membrane by palmitoylation. The membrane localization of the effectors strongly influences the phenotypes they trigger in the plant. Agrobacterium-mediated expression of xopE1 and xopJ in Nicotiana benthamiana led to cell-death reactions that, for xopJ, were dependent on the N-myristoylation motif. In the case of xopE1(G2A), cell death was more pronounced with the mutant than with the wild-type protein. In addition, XopE2 has an avirulence activity in Solanum pseudocapsicum.
Automatic web news extraction using tree edit distance (2004)

The Web poses itself as the largest data repository ever available in the history of humankind. Major efforts have been made in order to provide efficient access to relevant information within this huge repository of data. Although several techniques have been developed to the problem of Web data extraction, their use is still not spread, mostly because of the need for high human intervention and the low quality of the extraction results.In this paper, we present a domain-oriented approach to Web data extraction and discuss its application to automatically extracting news from Web sites. Our approach is based on a highly efficient tree structure analysis that produces very effective results. We have tested our approach with several important Brazilian on-line news sites and achieved very precise results, correctly extracting 87.71% of the news in a set of 4088 pages distributed among 35 different sites.
Material simulation-based electronic device prognosis (2005)

Electronic systems, such as power supplies, are complex multilayered devices consisting of different materials with inherent variability. Thermal gradient cycling occurs during system operation which eventually results in thermo-mechanical fatigue induced failure. Such failures can result in immediate electronic system shutdown with no advanced fault or warning signals; thus preventing the use of conventional fault-to-failure detection approaches as a means of predicting maintenance need. This NAVAIR sponsored SBIR project uses state-of-the-art material modeling to predict degradation of circuit board elements as a means for "simulated fault detection." This effort has been focused on the specific aspect of solder fracture and fatigue since electronic industry statistics have attributed this failure issue as a driving factor in system reliability. This project demonstrates feasibility for using conventional, off-the-shelf sensing, to predict solder degradation due to thermal cycling as a means to prognosticate electronic device reliability
The RNA recognition motif of NIFK is required for rRNA maturation during cell cycle progression (2015)

Ribosome biogenesis governs protein synthesis. NIFK is transactivated by c-Myc, the key regulator of ribosome biogenesis. The biological function of human NIFK is not well established, except that it has been shown to interact with Ki67 and NPM1. Here we report that NIFK is required for cell cycle progression and participates in the ribosome biogenesis via its RNA recognition motif (RRM). We show that silencing of NIFK inhibits cell proliferation through a reversible p53-dependent G1 arrest, possibly by induction of the RPL5/RPL11-mediated nucleolar stress. Mechanistically it is the consequence of impaired maturation of 28S and 5.8S rRNA resulting from inefficient cleavage of internal transcribed spacer (ITS) 1, a critical step in the separation of pre-ribosome to small and large subunits. Complementation of NIFK silencing by mutants shows that RNA-binding ability of RRM is essential for the pre-rRNA processing and G1 progression. More specifically, we validate that the RRM of NIFK preferentially binds to the 5'-region of ITS2 rRNA likely in both sequence specific and secondary structure dependent manners. Our results show how NIFK is involved in cell cycle progression through RRM-dependent pre-rRNA maturation, which could enhance our understanding of the function of NIFK in cell proliferation, and potentially also cancer and ribosomopathies.
Large-Scale Asymmetric Synthesis of the Bioprotective Agent JP4-039 and Analogs (2011)

JP4-039 is a novel nitroxide conjugate capable of crossing lipid bilayer membranes and scavenging reactive oxygen species (ROS). An efficient and scalable one-pot hydrozirconation-transmetalation-imine addition methodology has been developed for its asymmetric preparation. Furthermore, this versatile methodology allows for the synthesis of cyclopropyl and fluorinated analogs of the parent lead structure.
PTEN Mutation Spectrum and Genotype-Phenotype Correlations in Bannayan-Riley-Ruvalcaba Syndrome Suggest a Single Entity With Cowden Syndrome (1999)

Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway. CS is characterized by multiple hamartomas and an increased risk of benign and malignant disease of the breast, thyroid and central nervous system, whilst the presence of cancer has not been formally documented in BRR. The partial clinical overlap in these two syndromes is exemplified by the hallmark features of BRR: macrocephaly and multiple lipomas, the latter of which occur in a minority of individuals with CS. Additional features observed in BRR, which may also occur in a minority of CS patients, include Hashimoto's thyroiditis, vascular malformations and mental retardation. Pigmented macules of the glans penis, delayed motor development and neonatal or infant onset are noted only in BRR. In this study, constitutive DNA samples from 43 BRR individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both CS and BRR, were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) BRR cases. Genotype-phenotype analyses within the BRR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, BRR or BRR/CS overlap family ( P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family ( P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRR patients ( P = 0.028). In contrast to a prior report, no significant difference in mutation status was found in familial versus sporadic cases of BRR ( P = 0.113). Comparisons between BRR and a previously studied group of 37 CS families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CS alone or both CS and BRR when compared with BRR alone ( P = 0.002). Among CS, BRR and BRR/CS overlap families that are PTEN mutation positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS and BRR may be different presentations of a single syndrome and, hence, both should receive equal attention with respect to cancer surveillance.
A Method for Determination of Particle Magnetic Susceptibility with Analytical Magnetapheresis (2000)

We recently developed a new method for simple determination of particle magnetic susceptibility using analytical magnetapheresis. This new method does not require laborious calibration plots and trial susceptibility values as do previous analytical magnetapheresis methods. The new method is based on balancing channel flow rates and magnetically induced flow rates for particle deposition in analytical magnetapheresis. The maximal flow rate for complete particle deposition was determined experimentally and set to equal the magnetically induced flow rate for determining particle magnetic susceptibility. This magnetic susceptibility determination generally takes less than 20 min. Several magnetically susceptible and ion-labeled particles were tested using this new method. The carrier magnetic susceptibilities were varied, and erbium ion-labeled particles were studied experimentally, resulting in successful susceptibility determinations of erbium ion-labeled particles and yeasts. The precision of each measurement was generally approximately 10%. Experimental determination of particle magnetic susceptibilities differed by less than 10% from reference measurements taken using a superconducting quantum interference device magnetometer. This method can determine minimal susceptibilities on the order of 10(-9) cgs. The minimum number of erbium labeling ions per particle required for complete deposition of silicas and yeasts was found to be 6.7 x 10(9). Analytical magnetapheresis shows good potential for use in simple determination of particle magnetic susceptibilities and should become a useful technique.
Demonstration of 125-Gbps optical interconnects integrated with lasers, optical splitters, optical modulators and photodetectors on a single silicon substrate (2012)

One of the most serious issues in information industries is the bandwidth bottleneck in inter-chip interconnects. We propose a photonics-electronics convergence system to solve this issue. We fabricated a high density optical interposer to demonstrate the feasibility of the system by using silicon photonics integrated with an arrayed laser diode, an optical splitter, silicon optical modulators, germanium photodetectors, and silicon optical waveguides on a single silicon substrate. Error-free data transmission at 12.5 Gbps and a transmission density of 6.6 Tbps/cm<sup>2</sup> were achieved with the optical interposer. We believe this technology will solve the bandwidth bottleneck problem in the future.
ISFET Affinity Sensor (2003)

The so-called ion-step method represents a newly developed measurement concept for potentiometric detection and quantification of adsorbed biomolecules in which modified ion-sensitive field-effect transistors (ISFETs) are used. The ion-step method is based on a dynamic measuring principle, whereas many other potentiometric methods are static and measure in a state of thermo-dynamic equilibrium. A number of authors report on measuring protein adsorption by equilibrium potentiometry, but in all measurements the observed responses were poor (, ). The new measuring method is therefore an important alternative method for detection of adsorbed protein. In Subheading 1.2., a short explanation will be given for the disappointing results obtained with detection of protein by equilibrium potentiometry. Thereafter, the ion-step method will be described briefly and at the end of this introduction, the use of an ISFET affinity sensor for the measurement of heparin will be described.
Nanobody–Antigen Conjugates Elicit HPV-Specific Antitumor Immune Responses (2018)

High-risk human papillomavirus-associated cancers express viral oncoproteins (e.g., E6 and E7) that induce and maintain the malignant phenotype. The viral origin of these proteins makes them attractive targets for development of a therapeutic vaccine. Camelid-derived single-domain antibody fragments (nanobodies or VHHs) that recognize cell surface proteins on antigen-presenting cells (APC) can serve as targeted delivery vehicles for antigens attached to them. Such VHHs were shown to induce CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses against model antigens conjugated to them via sortase, but antitumor responses had not yet been investigated. Here, we tested the ability of an anti-CD11b VHH (VHH<sub>CD11b</sub>) to target APCs and serve as the basis for a therapeutic vaccine to induce CD8<sup>+</sup> T-cell responses against HPV<sup>+</sup> tumors. Mice immunized with VHH<sub>CD11b</sub> conjugated to an H-2D<sup>b</sup>-restricted immunodominant E7 epitope (E7<sub>49-57</sub>) had more E7-specific CD8<sup>+</sup> T cells compared with those immunized with E7<sub>49-57</sub> peptide alone. These CD8<sup>+</sup> T cells acted prophylactically and conferred protection against a subsequent challenge with HPV E7-expressing tumor cells. In a therapeutic setting, VHH<sub>CD11b</sub>-E7<sub>49-57</sub> vaccination resulted in greater numbers of CD8<sup>+</sup> tumor-infiltrating lymphocytes compared with mice receiving E7<sub>49-57</sub> peptide alone in HPV<sup>+</sup> tumor-bearing mice, as measured by <i>in vivo</i> noninvasive VHH-based immune-positron emission tomography (immunoPET), which correlated with tumor regression and survival outcome. Together, these results demonstrate that VHHs can serve as a therapeutic cancer vaccine platform for HPV-induced cancers. <i>Cancer Immunol Res; 6(7); 870-80. ©2018 AACR</i>.
Inhibition of Src with AZD0530 Reveals the Src-Focal Adhesion Kinase Complex as a Novel Therapeutic Target in Papillary and Anaplastic Thyroid Cancer (2009)

Inhibition of the Src-FAK complex represents a promising therapeutic strategy for patients with advanced thyroid cancer, and phospho-FAK represents a potential biomarker for response.
Targeting Cancer Stem Cells for Treatment of Glioblastoma Multiforme (2013)

Cancer stem cells (CSCs) in glioblastoma multiforme (GBM) are radioresistant and chemoresistant, which eventually results in tumor recurrence. Targeting CSCs for treatment is the most crucial issue. There are five methods for targeting the CSCs of GBM. One is to develop a new chemotherapeutic agent specific to CSCs. A second is to use a radiosensitizer to enhance the radiotherapy effect on CSCs. A third is to use immune cells to attack the CSCs. In a fourth method, an agent is used to promote CSCs to differentiate into normal cells. Finally, ongoing gene therapy may be helpful. New therapeutic agents for targeting a signal pathway, such as epidermal growth factor (EGF) and vascular epidermal growth factor (VEGF) or protein kinase inhibitors, have been used for GBM but for CSCs the effects still require further evaluation. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as cyclooxygenase-2 (Cox-2) inhibitors have proven to be effective for increasing radiation sensitivity of CSCs in culture. Autologous dendritic cells (DCs) are one of the promising immunotherapeutic agents in clinical trials and may provide another innovative method for eradication of CSCs. Bone-morphogenetic protein 4 (BMP4) is an agent used to induce CSCs to differentiate into normal glial cells. Research on gene therapy by viral vector is also being carried out in clinical trials. Targeting CSCs by eliminating the GBM tumor may provide an innovative way to reduce tumor recurrence by providing a synergistic effect with conventional treatment. The combination of conventional surgery, chemotherapy, and radiotherapy with stem cell-orientated therapy may provide a new promising treatment for reducing GBM recurrence and improving the survival rate.
Altered axonal architecture by removal of the heavily phosphorylated neurofilament tail domains strongly slows superoxide dismutase 1 mutant-mediated ALS (2005)

Eliminating assembled neurofilaments (NFs) from axons or misaccumulating NFs in motor neuron cell bodies strongly slows disease in mouse models of mutant superoxide dismutase 1 (SOD1)-induced amyotrophic lateral sclerosis. One proposal for how reducing axonal NFs can increase survival is that the multiphosphorylated tail domains of the two larger NF subunits act in motor neuron cell bodies as phosphorylation sinks where they mitigate cyclin-dependent kinase 5 dysregulation induced by mutant SOD1. Elimination by gene targeting in mice of the NF medium and NF heavy tail domains and their 58 known phosphorylation sites accelerates aberrant phosphorylation of other neuronal substrates while leaving overall NF content unaltered. However, disease onset is significantly delayed and survival is extended, inconsistent with the ameliorative property of altered NF content protecting by serving as substrates for dysregulation of any NF kinase. Moreover, at comparable disease stages significantly more surviving motor neurons and axons were found in SOD1 mutant mice deleted in the NF tails than in similar mice with wild-type NFs. This finding supports noncell autonomous toxicity in SOD1 mutant-mediated amyotrophic lateral sclerosis: removal of the NF tails slows damage developed directly within motor neurons, but SOD1 mutant damage within nonneuronal supporting cells reduces motor neuron functionality.
Labeling the peptidyltransferase center of the Escherichia coli ribosome with photoreactive tRNA(Phe) derivatives containing azidoadenosine at the 3' end of the acceptor arm: a model of the tRNA-ribosome complex. (1989)

Photoreactive derivatives of yeast tRNA(Phe) containing 2-azidoadenosine (2N3A) at position 73 or 76 have been crosslinked to the peptidyl site of Escherichia coli ribosomes. Covalent tRNA-ribosome attachment was dependent upon the replacement of adenosine by 2N3A in the tRNA, irradiation with 300-nm light, and the presence of poly(U). In all cases, the modified tRNAs became crosslinked exclusively to 50S ribosomal subunits. While the tRNA derivative containing 2N3A at position 73 labeled only protein L27, that containing 2N3A at position 76 labeled proteins L15, L16, and L27 as well as a segment of the 23S rRNA. The site of crosslinking in the rRNA was identified as guanosine-1945, which lies within a highly conserved sequence adjacent to a number of modified bases and has not until now been identified at the peptidyltransferase center. On the basis of these results, and previously reported crosslinks from tRNA containing 8-azidoadenosine in the 3'-terminal -A-C-C-A sequence [Wower, J., Hixson, S. S. & Zimmermann, R. A. (1988) Biochemistry 27, 8114-8121], we propose a model for the arrangement of tRNA molecules at the peptidyl and aminoacyl sites that is consistent with most of the information available about the location of the peptidyltransferase center and the decoding domain of the E. coli ribosome.
MPYS Is Required for IFN Response Factor 3 Activation and Type I IFN Production in the Response of Cultured Phagocytes to Bacterial Second Messengers Cyclic-di-AMP and Cyclic-di-GMP (2011)

Cyclic-di-GMP and cyclic-di-AMP are second messengers produced by bacteria and influence bacterial cell survival, differentiation, colonization, biofilm formation, virulence, and bacteria-host interactions. In this study, we show that in both RAW264.7 macrophage cells and primary bone marrow-derived macrophages, the production of IFN-β and IL-6, but not TNF, in response to cyclic-di-AMP and cyclic-di-GMP requires MPYS (also known as STING, MITA, and TMEM173). Furthermore, expression of MPYS was required for IFN response factor 3 but not NF-κB activation in response to these bacterial metabolites. We also confirm that MPYS is required for type I IFN production by cultured macrophages infected with the intracellular pathogens Listeria monocytogenes and Francisella tularensis. However, during systemic infection with either pathogen, MPYS deficiency did not impact bacterial burdens in infected spleens. Serum IFN-β and IL-6 concentrations in the infected control and MPYS(-/-) mice were also similar at 24 h postinfection, suggesting that these pathogens stimulate MPYS-independent cytokine production during in vivo infection. Our findings indicate that bifurcating MPYS-dependent and -independent pathways mediate sensing of cytosolic bacterial infections.