gebhart/patrepeval huggingface dataset:
Non-Invasive Imaging of Phosphoinositide-3-Kinase-Catalytic-Subunit-Alpha (PIK3CA) Promoter Modulation in Small Animal Models (2013)

Activation of the PI3K/Akt pathway, a critical step for survival in cancer cells is often associated with decreased sensitivity to several chemotherapeutic drugs. PIK3CA gene amplification is observed in 16-24% of epithelial ovarian cancer (EOC) patients in conjunction with p53 mutations. A 900 bp long PIK3CA promoter is shown to be negatively regulated by p53 in ovarian surface epithelial cells but the consequence of chemotherapeutic drug treatments on this promoter in ovarian cancer cells is largely unknown. We aim to study the modulation of this promoter by cisplatin using an improved fusion reporter in ovarian cancer cells and tumor xenografts by non-invasive imaging approach. A PIK3CA sensor was developed using a bi-fusion reporter from a newly constructed library of bi- and tri-fusion vectors comprising of two mutant far red fluorescent proteins (mcherry/mch and tdTomato/tdt), a mutant firefly luciferase (fluc2), and a PET reporter protein (ttk). In vivo imaging of mice implanted with 293T cells transiently expressing these bi- and tri-fusion reporters along with respective controls revealed comparable activity of each reporter in the fusion background and fluc2-tdt as the most sensitive one. Repression of the PIK3CA sensor by drugs was inversely proportional to cellular p53 level in a germline (PA1) and in an EOC (A2780) cell line but not in a p53 deficient EOC (SKOV3) cell line. Bioluminescence imaging of tumor xenografts stably expressing the PIK3CA sensor in PA1 and A2780 cells exhibited attenuating activity without any change in SKOV3 tumors expressing the PIK3CA sensor after cisplatin treatment. Sequential mutation at p53 binding sites showed gradual increase in promoter activity and decreased effects of the drugs. These newly developed PIK3CA-fluc2-tdt and the mutant reporter sensors thus would be extremely useful for screening new drugs and for functional assessment of PIK3CA expression from intact cells to living subjects.
Rapid, Cf-9- and Avr9-Dependent Production of Active Oxygen Species in Tobacco Suspension Cultures (1998)

The tomato Cf-9 gene confers resistance to races of Cla-dosporium fulvum expressing the corresponding avirulence gene Avr9. The availability of transgenic tobacco lines carrying Cf-9, and the well-characterized 28 amino acid Avr9 elicitor, make this an excellent system to study resistance gene function. In this paper we establish tobacco suspension cultures derived from transgenic tobacco plants containing Cf-9, as well as from plants without Cf-9. Cultures derived from Cf9 tobacco produce active oxygen species (AOS) within 5 min of treatment with pure or synthetic Avr9. This enabled us to perform biochemical and pharmacological analysis in cell culture of the very earliest events in resistance gene function. In addition to AOS production, an increase in oxygen uptake was detected in the Avr9-treated Cf9 cells. Both phenomena were inhibited by low concentrations of diphenyleneiodonium (DPI). Additional pharmacological inhibitor studies suggest that uptake of calcium, activation of protein kinases, and probably phospholipase A 2 (PLA 2 ) activity are intermediates in the Cf-9- and Avr9-dependent signaling pathway that leads to AOS production. Interestingly, those defense responses did not result in plant cell death.
Immune response to HIV (2013)

In the present review, we shall discuss the different components of the HIV-specific immune response elicited by the infection, the kinetics of these responses during primary infection and the changes following transition to the chronic phase of infection, and the functional profile of 'effective' versus 'noneffective' HIV-specific immune responses.
On Digital Signatures and Public-Key Cryptosystems. (1977)

It is shown that the single operation of raising a number to a fixed power modulo a composite modulus is sufficient to implement digital signatures: a way of creating for a (digitized) document a recognizable, unforgeable, document-dependent digitized signature whose authenticity the signer can not later deny. An electronic funds transfer system or electronic mail system clearly could use such a scheme, since the messages must be digitized in order to be transmitted.
Birth and Death of Genes and Functions in the β-Esterase Cluster of Drosophila (2009)

Here we analyze the molecular evolution of the beta-esterase gene cluster in the Drosophila genus using the recently released genome sequences of 12 Drosophila species. Molecular evolution in this small cluster is noteworthy because it contains contrasting examples of the types and stages of loss of gene function. Specifically, missing orthologs, pseudogenes, and null alleles are all inferred. Phylogenetic analyses also suggest a minimum of 9 gene gain-loss events; however, the exact number and age of these events is confounded by interparalog recombination. A previous enigma, in which allozyme loci were mapped to beta-esterase genes that lacked catalytically essential amino acids, was resolved through the identification of neighbouring genes that contain the canonical catalytic residues and thus presumably encode the mapped allozymes. The originally identified genes are evolving with selective constraint, suggesting that they have a "noncatalytic" function. Curiously, 3 of the 4 paralogous beta-esterase genes in the D. ananassae genome sequence have single inactivating (frame-shift or nonsense) mutations. To determine whether these putatively inactivating mutations were fixed, we sequenced other D. ananassae alleles of these four loci. We did not find any of the 3 inactivating mutations of the sequenced strain in 12 other strains; however, other inactivating mutations were observed in the same 3 genes. This is reminiscent of the high frequency of null alleles observed in one of the beta-esterase genes (Est7/EstP) of D. melanogaster.
The Economic Rationale for the HOLC (2013)

Abstract This chapter examines the rationale for the HOLC from a public policy perspective. The HOLC intervened in the credit and real estate markets by refinancing some distressed loans that private lenders would not. One factor separating the HOLC from other lenders was the HOLC's access to cheaper funding, as it could issue bonds that bore guarantees from the federal government at a time when private lenders faced unusual liquidity demands from their short-term creditors. In addition, the HOLC had the incentive to internalize, and, therefore, to reduce, the societal costs of foreclosures, unlike private lenders. The HOLC was, in short, a government-sponsored bad bank that bought troubled loans from private lenders, and then took control of restructuring and servicing the loans. Private lenders, individually or collectively, would not have modified most of these loans because they were illiquid and weighed the risks of redefault or extending unnecessary modifications more heavily than the HOLC.
Enabling Reusable Physical Design Flows with Modular Flow Generators (2021)

Achieving high code reuse in physical design flows is challenging but increasingly necessary to build complex systems. Unfortunately, existing approaches based on parameterized Tcl generators support very limited reuse and struggle to preserve reusable code as designers customize flows for specific designs and technologies. We present a vision and framework based on modular flow generators that encapsulates coarse-grain and fine-grain reusable code in modular nodes and assembles them into complete flows. The key feature is a flow consistency and instrumentation layer embedded in Python, which supports mechanisms for rapid and early feedback on inconsistent composition. The approach gradually types the Tcl language and allows both automatic and user-annotated static assertion checks. We evaluate the design flows of successive generations of silicon prototypes designed in TSMC16, TSMC28, TSMC40, SKY130, and IBM180 technologies, showing how our approach can enable significant code reuse in future flows.
A Working Description of the Penn State Apple Orchard Consultant, an Expert System (1992)

Agricultural production has evolved into a complex business. It requires the accumulation and integration of knowledge and information from many diverse sources, including marketing; horticulture; insect, mite, disease, and weed management; accounting; and tax laws. Emerging sustainable practices require even more information (to substitute for purchased inputs) for implementation. Farm managers seldom have at their disposal all information available in a usable form when major management decisions must be made. Increasingly, modern growers must become experts in the acquisition of information for decision making in order to remain competitive. However, because integrating and interpreting information from many sources may be beyond the means of individual growers, they use the expertise of agricultural specialists. Unfortunately, the assistance of these specialists is becoming relatively scarce even as the complexity of agriculture is increasing. To alleviate this problem, current information must be structured and organized into an accessible system for growers and agricultural specialists. Because no organized structure is available for information storage and retrieval, technical information is often lost or unavailable to potential users. The use of electronic
Fabrication of Photonic Crystals Consisting of Si Nanopillars by Plasma Etching Using Self-Formed Masks (1999)

We fabricated two dimensional photonic crystals (a square and a triangular lattice) with a photonic band gap (PBG) in the visible light range by periodically arranging Si nanopillars with a period of 270 nm. The pillar diameter and height are 50 nm and 1 µm, respectively. The fabrication process uses iron clusters as nuclei for self-formation of etching masks during electron cyclotron plasma etching with SF 6 gas at -135°C to obtain high-aspect-ratio Si nanopillars. The iron clusters are arranged by electron beam lithography. The reflection spectra of the square lattice photonic crystal have a peak around 570 nm for transverse magnetic polarization light while that for transverse electric polarization have a peak around 550 nm. This is consistent with our theoretical calculation that the photonic crystal has a PBG at these wavelengths.
Nanophotonics for a sustainable future (2023)

As the field matures, its researchers are finding practical applications in solar-energy harvesting, chemical manufacturing, optical refrigeration, and energy-efficient computing.
Dynamic channel hot-carrier degradation of NMOS transistors by enhanced electron-hole injection into the oxide (1987)

Hot-carrier stressing has been carried out on NMOS transistors under dynamic stressing conditions in which the drain voltage is kept constant and a square wave is applied to the gate such that electrons are injected into the oxide during the upper part of the cycle, while the lower part is varied so as to vary the oxide hole current. It is found that maximum degradation occurs when the hole current is maximum, indicating that the injection of both holes and electrons into the oxide is necessary for enhanced surface state generation, and supporting the model by which the trapping of holes and the subsequent neutralization by injected electrons leads to the formation of interface states.
Advances in C(sp2)−H/C(sp2)−H Oxidative Coupling of (Hetero)arenes Using 3d Transition Metal Catalysts (2021)

Abstract C−H/C−H oxidative coupling has emerged as a straightforward and powerful technique for the construction of (hetero)biaryls, with substantial application to drug discovery, agrochemicals, biology, and material sciences. Mainly aryl‐aryl, aryl‐heteroaryl, and heteroaryl‐heteroaryl couplings via double C( sp 2 )−H activation using 4d or 5d noble transition metal catalysts have been extensively studied. Considering the earth‐abundant and inexpensive nature of 3d transition metals, the sustainable development of C( sp 2 )−H/C( sp 2 )−H oxidative coupling employing such metal catalysts has gained significant attention. In this review, we present a comprehensive overview of C( sp 2 )−H/C( sp 2 )−H oxidative coupling of (hetero)arenes catalyzed by 3d transition metals. magnified image
Kinase Inhibitors in Signal Transduction Therapy (2011)

This chapter contains sections titled: VEGFR (Vascular Endothelial Growth Factor Receptor) Flt3 (FMS-Like Tyrosine Kinase 3) Bcr-Abl (Breakpoint Cluster Region–Abelson Murine Leukemia Viral Oncogene Homologue) EGFR (Epidermal Growth Factor Receptor) IGFR (Insulin-Like Growth Factor Receptor) FGFR (Fibroblast Growth Factor Receptor) PDGFR (Platelet-Derived Growth Factor Receptor) c-Kit Met (Mesenchymal-Epithelial Transition Factor) Src p38 MAPKs (Mitogen-Activated Protein Kinases) ERK1/2 JNK (c-Jun N-Terminal Kinase, MAPK8) PKC (Protein Kinase C) CDKs (Cyclin-Dependent Kinases) Auroras Akt/PKB (Protein Kinase B) Phosphoinositide 3-Kinases Syk (Spleen Tyrosine Kinase) JAK (Janus Kinase) Kinase Inhibitors in Inflammation and Infectious Diseases References
Note to Physicians and Sonographers on Potential Underestimation of Acoustic Safety Indexes for Diagnostic Array Transducers (2020)

Two scientists from the U.S. Food and Drug Administration comment on limitations of acoustic safety indexes that can arise from spatial averaging effects of hydrophones that are used to measure acoustic output.
Intracoronary electrocardiogram to guide percutaneous interventions in coronary bifurcations – a proof of concept: the FIESTA (Ffr vs. IcEcgSTA) study (2018)

Intracoronary ECG has a good ability to predict functionally significant stenosis at the SB after MV stenting during bifurcation PCI. This method provides a novel strategy to assess the significance of an SB lesion without the need of a pressure wire.
Toward a hydrogen-free reductive catalytic fractionation of wheat straw biomass (2023)

The reductive catalytic fractionation (RCF) is an attractive method for the conversion of lignin toward valuable low-molecular weight aromatics during the pretreatment of lignocellulosic biomass. A prominent limitation to the upscaling of such technology is represented by the use of pressurized hydrogen gas. In this contribution, the role of hydrogen gas within the RCF of wheat straw biomass is investigated. The use of H2 was shown to enhance lignin depolymerization, by virtue of an improved hydrogenolysis and hydrogenation of lignin fragments, with a yield of phenolic monomers that increased from ~12 wt% of acid-insoluble lignin in the initial biomass under inert atmosphere, up to ~25 wt% under H2, for a reaction in methanol, at 250 °C, with Ru/C. The adoption of methanol, ethanol and isopropanol as hydrogen-donor solvents was also investigated in the absence of H2, and the use of ethanol was found to give the highest yield of monophenolics (up to ~20 wt%) owing to a better balance between solvolysis, hydrogenolysis, and hydrogenation of lignin. Nevertheless, a substantial loss of the carbohydrate fraction was observed for reactions performed at 250 °C, irrespective of hydrogen pressure and of the solvent employed. The use of a lower temperature of 200 °C in combination with H3PO4 resulted in an improved recovery of cellulose in the pulp and in the solubilization of hemicellulose and lignin, with the formation of monosaccharides (~14 wt% of polysaccharides in the initial biomass) and phenolic monomers (up to 18 wt%, in the absence of H2). Overall, the obtained results show that a tradeoff exists between the removal of H2 from the process and the production of low-MW phenolics during RCF, which can be improved by accurately tuning the process conditions.
Laser heating of aqueous samples on a micro-optical-electro-mechanical system (2023)

A system of heating a sample on a microchip includes the steps of providing a microchannel flow channel in the microchip; positioning the sample within the microchannel flow channel, providing a laser that directs a laser beam onto the sample for heating the sample; providing the microchannel flow channel with a wall section that receives the laser beam and enables the laser beam to pass through wall section of the microchannel flow channel without being appreciably heated by the laser beam; and providing a carrier fluid in the microchannel flow channel that moves the sample in the microchannel flow channel wherein the carrier fluid is not appreciably heated by the laser beam.
Remarkable reduction of threshold current density by substrate misorientation effects in 660 nm visible light lasers with GaInP bulk active layers (1992)

660 nm wavelength GaInP/AlInP visible lasers with 60 nm thick GaInP active layers were grown on misoriented (100) GaAs substrates by gas source molecular beam epitaxy. A remarkable reduction in threshold current density Jth was observed with increasing substrate misorientation angle (SMA) from the (100) surface toward the [011] direction. Jth was 1.23 kA/cm2 on average for SMA of 0°, and 841 A/cm2 for SMA of 15° (both cavity lengths were 600 μm). For 1.1 mm long cavity lasers, a minimum Jth was 702 A/cm2 which was obtained for ordinary bulk-crystal active layers without strain and quantum-well effects. Such misorientation effects on reduction of Jth was systematically discussed in relation to various lasing parameters.
Changes in CpG islands methylation patterns during ductal breast carcinoma progression. (2008)

2646 Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during carcinogenesis and this epigenetic change has been considered as a potential molecular marker for cancer. It would be very important to identify new cancer specific epigenetic alterations in different stages of tumor type to elucidate its tumorigenesis and clinical management.  We examined the changes in methylation patterns of several genes (ESR1, APC, CDH1, CTNNB1, GSTPI, THBS1, MGMT, TMS1 and TIMP3) by candidate gene approach during ductal breast cancer progression from atypical ductal hyperplasia to in situ and invasive carcinoma. Twenty age-matched normal and paired samples of synchronous pre invasive lesions (Atypical Ductal Hyperplasia and/or Ductal Carcinoma in situ) and invasive ductal breast carcinoma from 31 patients were studied. By establishing an empiric cutoff value, we calculated the frequency of methylation in tumors of different types of paired samples and controls and finally for validation of the frequency of methylation we tested additional isolated lesion 8 DCIS AND 16 IDC from 24 samples. Overall, 95 pathological samples and 20 normal breast tissues were analyzed by Quantitative Methylation Specific PCR (QMSP). APC, CDH1, and CTNNB1 promoter regions showed an increase in frequency of methylation and increased methylation levels in pathological samples when compared with normal breast tissues. The analysis of the syncronous paired breast lesions demonstrated an increase in methylation frequency and level for APC, CDH1, and CTNNB1 genes during progression. By establishing a cutoff value, we were able to distinguish among pre-invasive and invasive lesions. Synchronous methylation of APC, CDH1, and CTNNB1 was associated only with invasive lesions, whereas simultaneous methylation of APC and CDH1 or APC and CTNNB1 were more frequent in ductal carcinoma in situ and invasive carcinoma. Our data point to direct involvement of APC, CDH1, and CTNNB1 CpG island promoter methylation in the early stages of breast cancer progression, and suggest that these molecular alterations might be involved in the transition to an invasive phenotype.
A numerical study of three-dimensional incompressible flow around multiple posts (1986)

The incompressible laminar flow around single and double rows of an infinite number of posts between two flat plates has been calculated numerically. A C-grid with periodic boundary conditions has been used. The angle of attack, measured from the line normal to the row of posts, was varied between zero and less than 90 deg. The pressure loading was computed for all of the posts in each of these cases. Most of these calculations have been carried out on the Numerical Aerodynamic Simulation Cray 2 at NASA Ames Research Center.
Abstract 5355: Multiple mutations to the same gene are selected for and cooperate to drive cancer (2018)

Abstract Cancers accumulate oncogenic mutations whose biochemical impact depends upon other germline and somatic variants in the cell. It stands to reason that the consequence of a somatic mutation is mediated by the presence of additional genetic variants within the same gene, and by the allele on which they arise. We have undertaken integrative analyses of 27,534 human tumors, including 19,640 prospectively sequenced advanced and metastatic cancers, and revealed a startling rate of multiple non-synonymous somatic mutations in the same cancer gene and tumor, hereafter referred to as multiple mutations. Overall, 26% of primary and metastatic tumors had at least one cancer gene with two or more somatic mutations. A minority of multiple mutations arose from somatic hypermutation or as secondary mutations driving resistance to molecularly targeted therapy. Clonality analysis further indicated that the majority of multiple mutations were present in the same cell. Multiple cancer genes were enriched for a greater burden of multiple mutations than would be expected in the absence of selection, including APC, B2M, EGFR, and TERT. The allelic configuration of these mutations indicated that while multiple mutations in trans arose predominantly in tumor suppressor genes, consistent with the selective pressure for biallelic inactivation, the majority of phaseable mutations arose in cis in both tumor suppressors and oncogenes, implying a selective pressure exists for a biochemical function distinct from individual driver mutations in the same gene. Collectively, these data argue that multiple genetic variants within a gene and their allelic configurations can interact to drive cancers. Citation Format: Alexander N. Gorelick, Ed Reznik, Yanyan Cai, Craig Bielski, Chaitanya Bandlamudi, Alexander Penson, Philip Jonsson, Konnor La, Maurizio Scaltriti, Nikolaus Schultz, Barry S. Taylor. Multiple mutations to the same gene are selected for and cooperate to drive cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5355.
TOGA (2022)

Testing is widely recognized as an important stage of the software development lifecycle. Effective software testing can provide benefits such as bug finding, preventing regressions, and documentation. In terms of documentation, unit tests express a unit's intended functionality, as conceived by the developer. A test oracle, typically expressed as an condition, documents the intended behavior of a unit under a given test prefix. Synthesizing a functional test oracle is a challenging problem, as it must capture the intended functionality rather than the implemented functionality.
La fiscalité carbone aux frontières et ses effets redistributifs : Étude des effets redistributifs sur les revenus des ménages français d’une taxe carbone aux frontières (2020)

La mesure des émissions carbone est devenue un enjeu essentiel du XXIe siècle, dans un contexte ou l'humanité doit réduire drastiquement ses émissions de gaz à effet de serre si elle souhaite pouvoir limiter la hausse des températures à un niveau de 2°C. L'essor des échanges commerciaux et la globalisation de la chaine de valeur rendent par ailleurs de plus en difficile la traçabilité des impacts climatiques et environnementaux des biens et des produits que nous consommons en France. Le concept d'empreinte carbone s'inscrit dans une démarche complémentaire à celle des inventaires nationaux de gaz à effet de serre généralement utilisés dans le cadre des négociations internationales autour des enjeux climatiques, en proposant d'imputer l'ensemble des émissions induites par un processus de production d'un bien ou d'un service, à son consommateur final.