gebhart/patrepeval huggingface dataset:
Abstract 2980: Maximizing the efficacy of anti-angiogenesis cancer therapy: A multi-targeting strategy by tyrosine kinase inhibitors (2014)

Abstract Although vascular endothelial growth factor (VEGF) inhibitors provide significant clinical benefit, they often require dose reductions or even withdrawals due to their severe toxicities. Furthermore, almost all cancers show intrinsic and/or evasive resistance to VEGF inhibitors by multiple mechanisms. Serum angiopoietin-2 (Ang2) level has been proposed as a potential biomarker of VEGF inhibitor response in several cancers. Response to lenvatinib (E7080; VEGFR1-3 inhibitor) is also reported to correlate with low Ang2 level in differentiated thyroid cancer and endometrial cancer. From these clinical observations, Ang2 and its receptor Tie2 has been focused as promising targets. Here, we demonstrated mechanisms of resistance induced by Ang2 and a novel strategy to circumvent the resistance by combination of multi-tyrosine kinase inhibitors (TKIs), lenvatinib and golvatinib (E7050; c-Met, Tie2, EphB4 inhibitor). Tie2 defines a highly pro-angiogenic macrophage subset, Tie2-expressing macrophage (TEM). Ang-Tie2 and EphB4-EphrinB2 signaling play critical roles in pericyte-mediated vessel stabilization. Ectopic expression of Ang2 in thyroid cancer conferred resistance to lenvatinib and enhanced pericyte-associated endothelial network development and TEM infiltration. In vitro analyses suggested that golvatinib/lenvatinib combination inhibited pericyte-mediated vessel stabilization and TEM differentiation. In thyroid and endometrial cancer models, golvatinib/lenvatinib combination inhibited pericyte network development and TEM infiltration, resulting in severe perfusion disorder and massive apoptosis. Body weight loss was tolerable in mice, and no macroscopic change was observed. These results suggest that modulation of tumor microenvironment by strategic and well-tolerated combination of multi-targeting TKIs sensitizes cancer to VEGF inhibitors, which warrants further clinical investigation to determine the clinical benefit of anti-angiogenesis cancer therapy. Citation Format: Youya Nakazawa, Satoshi Kawano, Junji Matsui, Yasuhiro Funahashi, Osamu Tohyama, Hiroki Muto, Takayuki Nakagawa, Tomohiro Matsushima. Maximizing the efficacy of anti-angiogenesis cancer therapy: A multi-targeting strategy by tyrosine kinase inhibitors. [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 2980. doi:10.1158/1538-7445.AM2014-2980
A dynamically reconfigurable interconnection chip (1987)

This paper will describe a 70K transistor chip fabricated in a 1.25μm CMOS technology, with a 6.2×7.6mm die size, and featuring data synchronization, pipeline latency compensation and other computational elements.
Multiplexed Detection of mRNA Using Porosity-Tuned Hydrogel Microparticles (2012)

Transcriptional profiling, which is directly or indirectly associated with expressed protein levels, has been used in various applications including clinical prognosis and pharmaceutical investigation of drug activities. Although the widely used reverse transcription polymerase chain reaction (RT-PCR) allows for the quantification of absolute amounts of mRNA (mRNA) from inputs as small as a single cell, it is an indirect detection method that requires the amplification of cDNA copies of target mRNAs. Here, we report the quantification of unmodified full-length transcripts, using poly(ethylene) glycol diacrylate (PEGDA) hydrogel microparticles synthesized via stop flow lithography (SFL). We show that PEG600 serves as an effective porogen to allow for the capture of large (∼1000-3700 nt long) mRNAs. Our relatively simple hydrogel-based mRNA detection scheme uses a multibiotinylated universal label probe and provides assay performance (limit of detection of ∼6 amol of an in-vitro-transcribed model target) comparable to an existing commercial bead-based technology that uses branched DNA (bDNA) signal amplification. We also demonstrate a 3-plex mRNA detection, without cross-reactivity, using shape-encoded "intraplex" hydrogel microparticles. Our ability to tune the porosity of encoded hydrogel microparticles expands the utility of this platform to now quantify biomacromolecules ranging in size from large mRNAs to small miRNAs.
Alterations in protein secretion caused by metabolic engineering of glycosylation pathways in fungi. (2008)

Due to its natural properties, Trichoderma reesei is commonly used in industry-scale production of secretory proteins. Since almost all secreted proteins are O-glycosylated, modulation of the activity of enzymes of the O-glycosylation pathway are likely to affect protein production and secretion or change the glycosylation pattern of the secreted proteins, altering their stability and biological activity. Understanding how the activation of different components of the O-glycosylation pathway influences the glycosylation pattern of proteins and their production and secretion could help in elucidating the mechanism of the regulation of these processes and should facilitate creation of engineered microorganisms producing high amounts of useful proteins. In this review we focus on data concerning Trichoderma, but also present some background information allowing comparison with other fungal species.
The E2 "gene" of bovine papillomavirus encodes an enhancer-binding protein. (1987)

The E2 early open reading frame (presumably gene) of bovine papillomavirus-1 was fused in frame with the collagen-beta-galactosidase-encoding region of the vector pJG200 and was expressed in and partially purified from Escherichia coli. The hybrid protein specifically bound to the enhancer region of bovine papillomavirus at several sites. DNase I-cleavage protection analysis of one such site revealed the protected sequence. A comparison of the protected sequence with the remainder of the DNA sequences that also have affinity for the protein revealed a consensus sequence having the motif AATTGGCGGNNCG, in which N is any nucleotide. The protected region also includes a sequence with 2-fold rotational symmetry--ATCGGTG/CACCGAT.
Increased osteoblast functions in the presence of BMP‐7 short peptides for nanostructured biomaterial applications (2008)

To improve bone regeneration around orthopedic biomaterials, researchers have attempted to combine growth factors on and in implants. Equally as exciting, greater bone growth has been demonstrated around nanoscaled materials (like helical rosette nanotubes or nanocrystalline hydroxyapatite) that mimic the geometry of the natural components of bone. To combine these two approaches, in this in vitro study, the ability of three short peptides [labeled for convenience: a or SNVILKKYRN, b or KPSSAPTQLN, and c or KAISVLYFDDS chosen from the larger bone morphogenetic protein-7 (BMP-7)] to promote osteoblast (bone-forming cells) functions were determined. Shorter peptides of BMP-7 are required for growth factor incorporation into nanoscale biomaterials because their sizes are in the nanometer regime. Results showed that of all the peptides, peptide b and the peptide combination a,b, enhanced osteoblast density the most after 5 days when compared with the controls (no growth factors). Furthermore, osteoblasts cultured with peptide b had a larger and more spread morphology than did controls. In addition, peptide c and its combinations (a, c; b, c; and a, b, c) increased osteoblast calcium deposition after 14 and 21 days compared with the controls. Since these peptides are much smaller than BMP-7, the results of this study provided information that peptides can be easily chemically functionalized onto nanoscaled biomaterials to improve bone growth. Thus, the present study elucidated that shorter peptides in BMP-7 was found to be more appropriate for inclusion in and on nanomaterials to promote osteoblast proliferation (peptide b and the peptide combination a,b) and osteoblast deposition of calcium-containing mineral (peptide c and the peptide combinations a,c; b,c; and a, b, c).
Constitutive activation of JAK–STAT3 signaling by BRCA1 in human prostate cancer cells (2001)

Germ-line mutations of the breast cancer susceptibility gene 1 (BRCA1) confer a high risk for breast and ovarian cancer in women and prostate cancer in men. The BRCA1 protein contributes to cell proliferation, cell cycle regulation, DNA repair and apoptosis; however, the mechanisms underlying these functions of BRCA1 remain largely unknown. Here, we showed that, in Du-145 human prostate cancer cells, enhanced expression of BRCA1 resulted in constitutive activation of signal transducer and activator transcription factor 3 (STAT3) tyrosine and serine phosphorylation. Moreover, Janus kinase 1 (JAK1) and JAK2, the upstream activators of STAT3, were also activated by BRCA1. Immunoprecipitation assay showed that BRCA1 interacted with JAK1 and JAK2. Blocking STAT3 activation using antisense oligonucleotides significantly inhibited cell proliferation and triggered apoptosis in Du-145 cells with enhanced expression of BRCA1. These findings indicate that BRCA1 interacts with the components of the JAK-STAT signaling cascade and modulates its activation, which may provide a new critical survival signal for the growth of breast, ovarian and prostate cancers in the presence of normal BRCA1.
Avian pneumoviruses and emergence of a new type in the United States of America (2000)

Avian pneumovirus (APV) primarily causes an upper respiratory disease recognized as turkey rhinotracheitis (TRT) or swollen head syndrome (SHS) in chickens. The virus was first isolated in South Africa during the early 1970s and has subsequently been reported in Europe, Asia and South America. In February 1997, a serologically distinct APV isolate was officially reported in the USA following an outbreak of TRT during the previous year. This was the first report of these virus types in the USA; they were previously considered exotic to the USA and Canada. The predicted matrix (M) proteins of European APV type A and B isolates share 89% identity in their amino acid sequence. However, the predicted M protein of APV/CO is only 78% similar to the APV type A and 77% similar to the APV type B protein sequence. The predicted amino acid sequence of the US APV isolate's fusion (F) protein has 72% sequence identity to the F protein of APV type A and 71% sequence identity to the F protein of type B. This compares with the 83% sequence identity between the predicted amino acid sequences of the F proteins of APV types A and B. The lack of sequence heterogeneity among the US APV isolates over 2 years suggests that these viruses have maintained a relatively stable population since the first outbreak of TRT. Phylogenetic analysis of the M and F proteins, together with the serological uniqueness of the US APV isolates, supports their classification as a new APV, designated type C.
Serum vasopressin concentrations in critically ill patients* (2006)

AVP serum concentrations 24 hrs after intensive care unit admission were significantly increased in this mixed critically ill patient population. The lack of a correlation between AVP serum concentrations and hemodynamic parameters suggests complex dysfunction of the vasopressinergic system in critical illness. Relative and absolute AVP deficiency may be infrequent entities during acute surgical critical illness, mostly remaining without significant effects on cardiovascular function.
Roll‐to‐roll manufacturing of electronics on flexible substrates using self‐aligned imprint lithography (SAIL) (2009)

Abstract— The manufacture of large‐area arrays of thin‐film transistors on polymer substrates using roll‐to‐roll (R2R) processes exclusively is being developed. Self‐aligned imprint lithography (SAIL) enables the patterning and alignment of submicron‐sized features on meter‐scaled flexible substrates in the R2R environment. SAIL solves the problem of precision interlayer registry on a moving web by encoding all the geometry information required for the entire patterning steps into a monolithic three‐dimensional imprint with discrete thickness modulation. The pre‐aligned multiple‐step mask structure maintains its alignment regardless of subsequent substrate distortion. Challenges are encountered in relation to the novel nature of using flexible substrates and building toolsets for the R2R processing. In this paper, methods of the SAIL process, the resulting active‐matrix backplanes, the trajectory of SAIL process development, and the remaining issues for production are presented.
Laparoscopic Fluorescence Diagnosis for Intraabdominal Fluorescence Targeting of Peritoneal Carcinosis (2002)

Laparoscopic fluorescence diagnosis can increase the sensitivity and specificity of diagnostic staging laparoscopy. It allows determination of the extent of peritoneal carcinosis. Improved preoperative assessment helps to avoid unnecessary laparotomies and radical resections.
Characterization of Post-Transcriptionally Suppressed Transgene Expression That Confers Resistance to Tobacco Etch Virus Infection in Tobacco. (1997)

Tobacco lines expressing transgenes that encode tobacco etch virus (TEV) coat protein (CP) mRNA with or without nonsense codons give rise to TEV-resistant tissues that have reduced levels of TEV CP mRNA while maintaining high levels of transgene transcriptional activity. Two phenotypes for virus resistance in the lines containing the transgene have been described: immune (no virus infection) and recovery (initial systemic symptoms followed by gradual recovery over several weeks). Here, we show that at early times in development, immune lines are susceptible to TEV infection and accumulate full-length CP mRNA. Therefore, immune lines also exhibit meiotic resetting, as is seen in the recovery lines, providing molecular evidence for a common mechanism of gene silencing and virus resistance in both cases. We also investigated the characteristics of two sets of low molecular weight RNAs that appear only in silenced tissue. One set has nearly intact 5[prime] ends, lacks poly(A) tails, and is associated with polyribosomes; the second set contains the 3[prime] end of the mRNA. Treating silenced leaf tissue with cycloheximide resulted in decreased levels of full-length mRNA and an increase in the levels of the low molecular weight RNAs, supporting a cytoplasmic decay mechanism that does not require ongoing translation. Surprisingly, mRNA from the transgene containing nonsense codons was associated with more ribosomes than expected, possibly resulting from translation from a start codon downstream of the introduced translational stop codons. We present a hypothesis for transgene/viral RNA degradation in which RNA degradation occurs in the cytoplasm while in association with polyribosomes.
Cytokinins. New Insights into a Classic Phytohormone (2002)

Cytokinins were discovered in the search for factors that promoted division of plant cells in culture.Naturally occurring cytokinins are N 6 -substituted adenine derivatives that generally contain an isoprenoid derivative side chain.These hormones influence numerous aspects of plant development and physiology, including seed germination, de-etiolation, chloroplast differentiation, apical dominance, plantpathogen interactions, flower and fruit development, and leaf senescence.These processes are also influenced by various other stimuli (e.g.light and other phytohormones), and the physiological and develop-
Gender-Based Differences in Outcome in Patients With Sepsis (1999)

Female gender is an independent predictor of increased mortality in critically ill surgical patients with documented infection.
Nanoimprint lithography (1996)

Nanoimprint lithography, a high-throughput, low-cost, nonconventional lithographic method proposed and demonstrated recently, has been developed and investigated further. Nanoimprint lithography has demonstrated 25 nm feature size, 70 nm pitch, vertical and smooth sidewalls, and nearly 90° corners. Further experimental study indicates that the ultimate resolution of nanoimprint lithography could be sub-10 nm, the imprint process is repeatable, and the mold is durable. In addition, uniformity over a 15 mm by 18 mm area was demonstrated and the uniformity area can be much larger if a better designed press is used. Nanoimprint lithography over a nonflat surface has also been achieved. Finally, nanoimprint lithography has been successfully used for fabricating nanoscale photodetectors, silicon quantum-dot, quantum-wire, and ring transistors.
125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts. (1976)

125I-labeled human epidermal growth factor (hEGF) binds in a specific and saturable manner to human fibroblasts. At 37 degrees C, the cell-bound 125I-hEGF initially may be recovered in a native form by acid extraction; upon subsequent incubation, the cell-bound 125I-hEGF is degraded very rapidly, with the appearance in the medium of 125I-monoiodotyrosine. At 0 degrees C, cell-bound 125I-hEGF is not degraded but slowly dissociates from the cell. The data are consistent with a mechanism in which 125I-hEGF initially is bound to the cell surface and subsequently is internlized before degradation. The degradation is blocked by inhibitors of metabolic energy production (azide, cyanide, dinitrophenol), some protease inhibitors (Tos-Lys-CH2Cl, benzyl guanidobenzoate), a lysosomotropic agent (chloroquine) various local anesthetics (cocaine, lidocaine, procaine), and ammonium chloride. After the binding and degradation of 125I-hEGF the fibroblasts are no longer able to rebind fresh hormone. The binding capacity of these cells is restored by incubation in a serum-containing medium; this restoration is inhibited by cycloheximide or actinomycin D.
Using designer's effort for user interface evaluation (2009)

Designing Human Computer Interfaces is one of the more important and difficult design tasks. The tools for verifying the quality of the interface are frequently expensive or provide feedback too far after the design of the interface as to make it meaningless. To improve the interface usability, designers need a verification tool providing immediate feedback at a low cost. Using an effort-based measure of usability, it is possible for a designer to estimate the effort a subject might expend to complete a specific task. In this paper, we develop the notion of designer's effort for evaluating interface usability for new designs and Commercial-Off-The-Shelf software. Designer's effort provides a technique to evaluate human interface before completing the development of the software and provides feedback from usability tests conducted using the effort-based evaluation technique.
Vaginal microbiome and sexually transmitted infections: an epidemiologic perspective (2011)

Vaginal bacterial communities are thought to help prevent sexually transmitted infections. Bacterial vaginosis (BV) is a common clinical syndrome in which the protective lactic acid-producing bacteria (mainly species of the Lactobacillus genus) are supplanted by a diverse array of anaerobic bacteria. Epidemiologically, BV has been shown to be an independent risk factor for adverse outcomes including preterm birth, development of pelvic inflammatory disease, and acquisition of sexually transmitted infections. Longitudinal studies of the vaginal microbiome using molecular techniques such as 16S ribosomal DNA analysis may lead to interventions that shift the vaginal microbiota toward more protective states.
Molecular Interactions between Two Global Regulators, sar and agr, in Staphylococcus aureus (1998)

The expression of many virulence determinants in Staphylococcus aureus is controlled by regulatory loci such as agr and sar. We have previously shown that the SarA protein is required for optimal transcription of RNAII and RNAIII in the agr locus. To define the specific molecular interaction, we overexpressed SarA as a glutathione S-transferase (GST) fusion protein by cloning the 372-base pair (bp) sarA gene into the vector. The purified GST-SarA as well as cleaved SarA were able to bind specifically to the P2, P3, and the combined P2-P3 promoter fragments of agr in gel shift assays. Using monoclonal antibodies to SarA, we found that SarA is a part of the retarded protein-DNA complex as evidenced by the formation of a supershifted band. The SarA binding site on the agr promoter, mapped by DNase I footprinting assay, covered a 29-bp region between the P2 and P3 promoters devoid of any direct repeats. A synthetic 45-bp fragment encompassing the 29-bp sequence also bound the SarA protein in band shift assays. Serial in-frame deletion analysis of sarA revealed that, with the exception of 15 residues in the N terminus, almost all of SarA (residues 16-124) is essential for agr binding activity. Northern analysis confirmed that only the sar mutant clone containing a truncated sarA gene with a 15-residue deletion in the N terminus (SarA16-124) could activate agr transcription to a level approaching that of the full-length counterpart (SarA1-124). Taken together, these data indicated that SarA is a DNA-binding protein with binding specificity to the P2 and P3 interpromoter region of agr, thereby activating RNAII and RNAIII transcription.
Room-temperature diphenyl-diacetylene liquid crystals (1992)

Thirty new asymmetric diphenyl-diacetylene (PTTP) liquid-crystal homologs are synthesized and their physical properties characterized. In addition to the observed high birefringence and relatively low viscosity, several dialkyl PTTP homologs also possess a low melting point, wide nematic range, and low heat of fusion enthalpy. These properties are highly desirable for forming eutectic mixtures with entirely PTTP components. A binary eutectic showing a nematic range from 10 to 98 °C is studied. These new liquid-crystal compounds and mixtures should be particularly useful for infrared applications.
Enzyme Activity and Organ Development in Newly Hatched Chicks Selected for High or Low Eight-Week Body Weight (1995)

Cockerels from lines of White Plymouth Rock chickens selected for 33 generations for high (HW) or low (LW) 8-wk BW were used in this experiment. Either Diet A (a diet similar to that under which selection had been conducted) or Diet B (containing 20% more CP and 20% more ME) were consumed ad libitum for the entire experiment (hatch to 6 wk of age). Body weights, organ weights, and enzymes present in the gastrointestinal tract (GIT) contents and pancreas were measured. There were differences between lines and between diets for BW and relative breast weight. Several organs (heart, lung, liver, and pancreas) generally remained a constant proportion of BW in both lines. Relative weight of the GIT was greater in HW cockerels from hatch to 10 d of age, after which relative GIT weight was greater in LW cockerels. Relative weight of the GIT was also affected after 10 d of age by density of feed. Interactions between line and diet were present for many digestive enzyme measurements, necessitating analyses within each main effect. All pancreatic enzymes except relative trypsin were higher in HW than LW cockerels. Although small intestine enzyme activities were higher in Line HW than LW, Cockerels on a relative basis the difference was present only for trypsin activity. Cockerels fed Diet B had higher levels of pancreatic chymotrypsin activity and of total and relative lipase activities than those fed Diet A.
Nanoparticles for Local Drug Delivery to the Oral Mucosa: Proof of Principle Studies (2010)

These data confirm nanoparticle internalization by OSCC cells and support the premise that nanoparticle-based delivery provides higher final intracellular levels relative to bolus administration. Furthermore, the penetration and subsequent internalization of nanoparticles within the proliferating basal layer cells demonstrates the feasibility of nanoparticle formulations for local delivery and stabilization of oral chemopreventive compounds.