gebhart/patrepeval huggingface dataset:
Abstract 4690: Next-generation screen for integrative subtyping and target discovery for KRAS-mutant cancer (2015)

Abstract Mutations in the small GTPase, KRAS, are found in ∼140,000 new cases of cancer every year in the United States. This heterogeneous class of cancers manifests primarily as adenocarcinomas of the lung, colon and pancreas. These cancers display a wide spectrum of KRAS-dependency and differentially activate downstream effector signaling. The tumors further diverge in their array of co-occurring secondary mutations, expression signatures and KRAS mutant allele. Ultimately, the sole trait these cancers share in common is an obstinate resistance to chemo- and targeted-therapies, making identification of effective treatments an urgent need. To identify treatments for such a heterogeneous class of cancers, we developed a strategy to stratify KRAS-mutant cell lines into subtypes by integrating next-generation RNAi screening and “Omics” database mining. Each subtype is characterized by unique biomarkers and distinct patterns of effector dependency, both of which represent potential targets for personalized therapeutic strategies. Our RNAi screen systematically evaluates sensitivity to siRNA-mediated knockdown of 40 KRAS effector nodes in a panel of 135 lung, colorectal and pancreatic cancer cell lines. Data is analyzed on the single cell level, through the simultaneous measurement of 5 functional parameters. This single-cell, multi-dimensional approach allows for a comprehensive assessment of cellular homeostasis, with unprecedented depth and dynamic range that allows robust classification of cell lines by similarity. We identify subtypes of KRAS-mutant cell lines that rely on particular effector pathways such as the RAL, RSK, MTOR and autophagy pathways, which are not engaged by all KRAS-mutant cell lines, and thus may represent targets for personalized treatment. We further identify widely shared dependencies such as on the RAF, glycolytic and cell cycle pathways. Through integrative data mining of exome, transcriptome and drug/siRNA sensitivity databases for each KRAS-mutant subtype, we can identify unique biomarkers that will serve to stratify patients in the clinic and recommend personalized treatment strategies. Citation Format: Tina L. Yuan, Rachel Bagni, Ming Yi, Arnaud Amzallag, Shervin Afghani, Katie Beam, William Burgan, Nicole Fer, Leslie Garvey, Brian Smith, Andrew Waters, Robert Stephens, Cyril Benes, Frank McCormick. Next-generation screen for integrative subtyping and target discovery for KRAS-mutant cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4690. doi:10.1158/1538-7445.AM2015-4690
Molecular predictors of outcome and response to bevacizumab (BEV) based on analysis of RTOG 0825, a phase III trial comparing chemoradiation (CRT) with and without BEV in patients with newly diagnosed glioblastoma (GBM). (2013)

LBA2010 Background: RTOG 0825 evaluated the addition of BEV to standard CRT in the treatment of GBM and included molecular stratification that assessed the degree of mesenchymal (MES) gene enrichment. We investigated the ability of the MES signature to predict response to BEV. Methods: Sufficient FFPE tissue for molecular analysis was available for 650 registered, eligible patients. TaqMan PCR was performed prospectively using the molecular stratifier on all patients and an expanded 43 member MES set on 234 cases. A subset of specimens was subjected to whole genome expression profiling (GEP). Predictive models were evaluated for their ability to predict survival (overall, OS, and progression-free, PFS) in the training cohort of the BEV arm after adjusting for prognostic factors and treatment arm. Unsupervised clustering of GEP data was used to identify molecular subsets and gene set enrichment analysis (GSEA) performed to evaluate for MES enrichment. Results: We observed a significant association between increasing MES signature and worse PFS and OS in the BEV arm (p=0.036 and p=0.032, respectively). Based on the association between high MES expression and poor outcome in the BEV arm, we sought to optimize a predictor using an expanded set of MES genes. Unbiased gene selection from a total of 43 genes followed by radial basis machine modeling identified a 10-gene predictor of outcome in the BEV arm (p&lt;0.001/HR 4.04 for OS and p&lt;0.001/HR 2.21 for PFS). To further support the association of MES enrichment and poor outcome in the BEV arm, we performed GEP. Unsupervised clustering identified a subtype of tumors with MES enrichment associated with the 10-gene predictor survival probability (p=0.0124, t-test). Ongoing studies will determine the extent to which this represents a predictive marker for BEV. Conclusions: We developed a 10-gene predictor specific to BEV treatment and suitable for FFPE that may serve to identify subsets of patients with newly diagnosed GBM who benefit from BEV. Supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and Brain SPORE P50 CA127001 from the NCI and Genentech. Clinical trial information: NCT00884741.
Automated Production Ramp-up Through Self-Learning Systems (2016)

The ramp-up of production systems is characterised by situations that arise for the first time. Due to the unpredictability of system behaviour in such situations, instabilities occur that lead to reduced production effectiveness. In order to deal with the resulting uncertainty, this paper presents an approach for self-directed systems capable of "learning", that is, they adapt their behaviour depending on the signals and changes of the circumfluent world. The advantages of such systems are significant, as they can react to changing products, production equipment and process constraints, and are able to function in exceptional situations. The presented concept makes use of reinforcement learning, one of the most general approaches to learning control. Simulations of three different ramp-up processes are used, where, as a demonstration, robots have to assemble windscreens on a moving truck.
Enzymatic Characterization of AMP Phosphorylase and Ribose-1,5-Bisphosphate Isomerase Functioning in an Archaeal AMP Metabolic Pathway (2012)

AMP phosphorylase (AMPpase), ribose-1,5-bisphosphate (R15P) isomerase, and type III ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) have been proposed to constitute a novel pathway involved in AMP metabolism in the Archaea. Here we performed a biochemical examination of AMPpase and R15P isomerase from Thermococcus kodakarensis. R15P isomerase was specific for the α-anomer of R15P and did not recognize other sugar compounds. We observed that activity was extremely low with the substrate R15P alone but was dramatically activated in the presence of AMP. Using AMP-activated R15P isomerase, we reevaluated the substrate specificity of AMPpase. AMPpase exhibited phosphorylase activity toward CMP and UMP in addition to AMP. The [S]-v plot (plot of velocity versus substrate concentration) of the enzyme toward AMP was sigmoidal, with an increase in activity observed at concentrations higher than approximately 3 mM. The behavior of the two enzymes toward AMP indicates that the pathway is intrinsically designed to prevent excess degradation of intracellular AMP. We further examined the formation of 3-phosphoglycerate from AMP, CMP, and UMP in T. kodakarensis cell extracts. 3-Phosphoglycerate generation was observed from AMP alone, and from CMP or UMP in the presence of dAMP, which also activates R15P isomerase. 3-Phosphoglycerate was not formed when 2-carboxyarabinitol 1,5-bisphosphate, a Rubisco inhibitor, was added. The results strongly suggest that these enzymes are actually involved in the conversion of nucleoside monophosphates to 3-phosphoglycerate in T. kodakarensis.
Distinct lineages of human T-cell clones, including Th17/Th1 cells, isolated at different stages of anti-factor VIII immune responses (48.26) (2009)

Abstract Approximately 25% of hemophilia A patients, who lack functional factor VIII (FVIII), develop neutralizing antibodies after receiving therapeutic infusions of FVIII. HLA-DRA-DRB1*0101-restricted T-cell clones that respond to FVIII2194-2213 were isolated from a hemophilia A subject (the proband) ~5 and 21 months following his development of a high-titer FVIII neutralizing antibody response, and from his brother who has not developed a clinically significant antibody response. Three clones obtained from the proband at 5 months were TH17/TH1-polarized and two were TH1/TH2-polarized. The 8 proband clones isolated at 21 months were TH2-polarized, indicating T-cell lineage changes over time. The 6 clones from the brother were TH1-polarized, indicating that B-cell tolerance to FVIII can be maintained even with circulating antigen-specific TH1-polarized cells. Several TCRBV-D-J junction sequences were identified suggesting differences in TCR interaction with the MHC class II-peptide complex. Current investigations are examining the response of clones to altered peptide ligands. This is the first evidence that TH17/TH1-polarized cells play a role in hemophilic immune responses to FVIII; it is also the first detailed characterization of antigen-specific TH17/TH1 clones isolated using standard culture conditions. Research Support: Bayer Hemophilia Award, CSL Behring Hemophilia Research Award, NIH.
Demonstration of a waveguide lens monolithically integrated with a laser diode by compositional disordering of a quantum well (1993)

An elliptic waveguide lens that is monolithically integrated with a GaAs/AlGaAs distributed feedback laser diode and a grating output coupler by electron beam lithography, ion implantation, and two-step metalorganic vapor phase epitaxy is described. The waveguide lens is formed by the etching of a patterning layer to ensure that the fabrication process of the waveguide lens is compatible with that of the laser diode. Collimated output light is directly obtained from a semiconductor substrate using this waveguide lens and a grating output coupler.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Atom smashers for profit and pleasure (1994)

Mention particle accelerators and the picture that usually comes to mind is of a complex structure, disappearing into the dark distance of some subterranean tunnel, which delivers highly relativistic particles to vast experimental halls. There, large teams of physicists search through the debris of innumerable interactions for the signatures of new particles. Exponential notation is appropriate for both budgets and particle energies and politics vies with physics in determining the way forward. Presented this way, particle accelerators may not seem a very attractive proposition for volume production by commercial companies, which need to see cash returns on investments in reasonable time-scales. Nevertheless, a number of companies do manufacture and sell complete systems, albeit on a more modest scale than the front-line instruments in major laboratories. So why do they do it?
Tunable Spin Loading and<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:msub><mml:mi>T</mml:mi><mml:mn>1</mml:mn></mml:msub></mml:math>of a Silicon Spin Qubit Measured by Single-Shot Readout (2011)

We demonstrate single-shot readout of a silicon quantum dot spin qubit, and we measure the spin relaxation time T1. We show that the rate of spin loading can be tuned by an order of magnitude by changing the amplitude of a pulsed-gate voltage, and the fraction of spin-up electrons loaded can also be controlled. This tunability arises because electron spins can be loaded through an orbital excited state. Using a theory that includes excited states of the dot and energy-dependent tunneling, we find that a global fit to the loading rate and spin-up fraction is in good agreement with the data.
A three-degree-of-freedom thin-film PZT-actuated microactuator with large out-of-plane displacement (2014)

A novel three degree-of-freedom microactuator based on thin-film lead-zirconate-titanate (PZT) is described with its detailed structural model. Its central rectangular-shaped mirror platform, also referred to as the stage, is actuated by four symmetric PZT bending legs such that each leg provides vertical translation for one corner of the stage. It has been developed to support real-time <i>in vivo</i> vertical cross-sectional imaging with a dual axes confocal endomicroscope for early cancer detection, having large displacements in three axes (z, θ<sub>x</sub>, θ<sub>y</sub>) and a relatively high bandwidth in the z-axis direction. Prototype microactuators closely meet the performance requirements for this application; in the out-of-plane (z-axis) direction, it has shown more than 177 <i>μ</i>m of displacement and about 84 Hz of structural natural frequency, when two diagonal legs are actuated at 14V. With all four legs, another prototype of the same design with lighter stage mass has achieved more than 430 <i>μ</i>m of out-of-plane displacement at 15V and about 200 Hz of bandwidth. The former design has shown approximately 6.4° and 2.9° of stage tilting about the x-axis and y-axis, respectively, at 14V. This paper also presents a modeling technique that uses experimental data to account for the effects of fabrication uncertainties in residual stress and structural dimensions. The presented model predicts the static motion of the stage within an average absolute error of 14.6 <i>μ</i>m, which approaches the desired imaging resolution, 5 <i>μ</i>m, and also reasonably anticipates the structural dynamic behavior of the stage. The refined model will support development of a future trajectory tracking controller for the system.
Correlation of Rickettsial Titers, Circulating Endotoxin, and Clinical Features in Rocky Mountain Spotted Fever (1983)

Blood rickettsial titers, skin biopsy results, and circulating endotoxin measurements were correlated with the clinical course of disease in patients with Rocky Mountain spotted fever (RMSF). Nine of 11 patients with documented RMSF had Rickettsia rickettsii isolated from plasma samples. Of the eight patients in whom rickettsial titers were measured, seven had 10(0.7) to 10(1.2) median tissue culture infective doses (TCID50) per milliliter; all seven had mild to moderately severe disease. One patient with fulminant, fatal untreated RMSF had 10(3) TCID50/mL of postmortem plasma. Two patients from whom rickettsiae were not isolated had positive direct immunofluorescent stains of skin biopsy material for R rickettsii. Circulating endotoxin was present in two patients, one with documented rickettsemia and one with a positive skin biopsy alone. Only low levels of circulating rickettsiae are present in patients with moderately severe disease. Measurement of plasma endotoxin is not useful in the early diagnosis of RMSF.
Supplementary Methods from MAPRE1 as a Plasma Biomarker for Early-Stage Colorectal Cancer and Adenomas (2023)

&lt;p&gt;Supplementary Methods&lt;/p&gt;
Supplementary Figures 1-6 from Loss of Aryl Hydrocarbon Receptor Promotes Colon Tumorigenesis in &lt;i&gt;Apc&lt;sup&gt;S580/+&lt;/sup&gt;; Kras&lt;sup&gt;G12D/+&lt;/sup&gt;&lt;/i&gt; Mice (2023)

&lt;p&gt;S1. Characterization of genotypes. S2. Loss of AhR increases non-phosphorylated β-catenin. S3. Intestinal pathology analysis from ACK and HACK mice. S4. AhR deletion promotes cell proliferation. S5. Intestinal pathology analysis from ACKG and HACKG mice. S6. Wnt signaling in Lgr5 haploinsufficient mice.&lt;/p&gt;
Syntheses, Characterizations, and Structures of a New Series of Aliphatic−Aromatic Polyesters. 1. The Poly(tetramethylene terephthalate dicarboxylates) (1999)

A new family of polyesters, the poly(tetramethylene terephthalate dicarboxylates) of formula [−O−CO−C6H4−CO−O−(CH2)x−O−CO−(CH2)y−CO−O−(CH2)x]n, was synthesized and characterized by 1H and 13C NMR in CDCl3 solution, infrared spectroscopy, molecular weight distribution, and X-ray fiber diffraction analysis. The 1H and 13C NMR spectroscopy and the molecular weight distribution confirm the homogeneous alternating distribution of the two kinds of diacids (aromatic and aliphatic). The crystal structures of the adipate and the succinate were determined by interpretation of their X-ray diffraction patterns. A dynamic infrared spectroscopic study confirmed the existence of a nongauche−nontrans torsion angle in the glycol segments, while the diacid moieties were in a nearly all-trans conformation.
Broadband packet switching: a personal perspective (2002)

The author's personal perspective on the development of broadband packet switching from 1980 to 1995 is presented in the context of the Internet's development during the same timeframe. The development of today's Internet is also placed into a 40-year perspective of a mature deployment of a national broadband packet infrastructure. A conclusion that today's Internet represents about 0.1 percent of the deployment of a national petabit per second capacity broadband packet network, and that we have moved roughly halfway through the development and deployment timeline is developed. Along the way, the author gives his personal perspective on the development of, and the researchers who developed, technologies like packet voice, Ethernet bridging, ATM, the CNRI gigabit testbeds, and local ATM. The article discusses the efforts at transitioning the Internet from academic to commercial service.
Predicted Structural Similarities of the DNA Binding Domains of c-Myc and Endonuclease Eco RI (1992)

The c-Myc oncoprotein belongs to a family of proteins whose DNA binding domains contain a basic region-helix-loop-helix (bHLH) motif. Systematic mutagenesis of c-Myc revealed that dimerized bHLH motifs formed a parallel four-helix bundle with the amino termini of helices 1 and 2 directed toward the inner and outer nucleotides of the DNA binding site, respectively. Both the basic region and the carboxyl-terminal end of the loop contributed to DNA binding specificity. The DNA binding domain of c-Myc may therefore be structurally similar to that of restriction endonuclease Eco RI.
Investigations in the tape-to-tape contact resistance and contact composition in superconducting CORC<sup>®</sup> wires (2022)

Abstract Conductor on Round Core (CORC ® ) wires and cables, constructed from multiple layers of helically wound REBa 2 Cu 3 O 7− δ tapes, are a promising cable technology for high field magnet applications. An important feature of high-temperature superconductor cables is the ability to share current between conductors, allowing current to bypass drops in I c and minimizing the risk of hot spot formation, which could lead to potential burnout in the superconductor. In contrast to stacked-tape cables, which have continuous contact between tapes, in CORC ® the transfer points occur at discrete tape crossovers. The tape-to-tape contact resistance, R c , plays a critical role in the current sharing capabilities and current distribution in cables. For the work reported here, special CORC ® wires were manufactured using different winding parameters to investigate variations in R c . Variations comprised inclusion of a lubricant, different lubricant conductivity, inclusion of pre-tinning, and heating briefly to melt the solder. Cables were first tested as straight lengths, followed by bending to a 10 cm diameter. In straight cables R c values ranged from 1 to over 1000 μ Ω cm 2 , depending on cabling parameters, with the highest values being found for cables made by the present ‘standard’ process. Bending the cables to a 10 cm diameter decreased R c by a factor 2–5. Tinning with PbSn decreased R c by three orders of magnitude compared to standard CORC ® wires, and heat treating wires with tinned conductor resulted in only a small further decrease in R c . Based on the measured R c at an electric field of 1 μ V cm −1 the resulting current transfer length between layers can range from a few millimeters to a tens of centimeters. Examination of contacts with a laser confocal microscope showed plastic deformation of the copper at the edges of the contact overlap area, apparently caused by thicker plating at tape edges digging into the copper of neighboring layers. These images reveal that only a fraction of the total contact surface may actually be touching when there is nothing to compensate for height differential. Images of the PbSn coated tapes indicated that application of solder produces a much more uniform contact surface and higher contact area. Furthermore, imaging of CORC ® cross-sections confirmed that in the non-tinned cables there are many regions where tapes are not in contact, while in contrast the PbSn cable shows significantly more contact between the tapes. These different imaging techniques reveal that tape surface morphology is a significant parameter in determining R c .
ChemInform Abstract: Hydrogen‐Bonding Receptors: Open‐Chain Catalytic Systems (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Efficient energy transfer between nanocrystalline YAG:Ce and TRITC (2004)

Luminescent nanocrystalline (NC) Ce3+-doped yttrium aluminum garnet (Y3Al5O12:Ce–YAG:Ce) is prepared by a combustion synthesis technique that yields a highly porous three-dimensional network of interconnected 18 nm nanocrystals. Tetramethyl rhodamine isothiocyanate (TRITC) was conjugated to NC YAG:Ce by using glycine as a bridging molecule. Efficient energy transfer is observed from the Ce3+ ions to the TRITC molecules upon photoexcitation of the NC YAG:Ce–TRITC conjugates.
Diagnostics of Plasma Pencil by Optical Emission Spectroscopy (2008)

Diagnostics of jet plasma discharge at atmospheric pressure by
optical emission spectroscopy.
Recent advances in mechanochromic luminescent metal complexes (2013)

Mechanochromic luminescent metal complexes have recently attracted considerable interest as smart materials for use in the fields of luminescence switches, mechanosensors, mechanohistory indicators, security papers, optoelectronic devices, and data storage. In this review, recent advancements in metal complex mechanochromic luminescence are summarized. The majority of the reported mechanochromic luminescent metal complex systems are discussed, including Zn(II), Au(I), Pt(II), Ag(I), Cu(I), Al(III), and Ir(III) complexes. Aggregation-induced emission (AIE) complexes are described based on the existence of a structural relationship between AIE compounds and mechanochromism. It is expected that AIE complexes may become important alternative sources of mechanochromic luminescent complexes.
Structural studies of the O‐specific polysaccharide from <i>Plesiomonas shigelloides</i> strain CNCTC 113/92 (2000)

The structure of the O-specific side chain of the lipopolysaccharide (LPS) of Plesiomonas shigelloides, strain CNCTC 113/92 has been investigated by NMR spectroscopy, matrix-assisted laser desorption/ionization time of flight mass spectrometry and sugar and methylation analysis. It was concluded that the polysaccharide is composed of a hexasaccharide repeating unit with the following structure: in which D-beta-D-Hepp is Dglycero-beta-Dmanno-heptopyranose and 6d-beta-D-Hep is 6-deoxy-beta-Dmanno-heptopyranose. This structure represents a novel hexasaccharide repeating unit of bacterial O-antigen that is characteristic and unique to the Plesiomonas shigelloides strain. Using the high-resolution magic angle spinning technique, 1H-NMR spectra were also obtained for the O-polysaccharide components of isolated LPS and in their original form directly on the surface of bacterial cells.