gebhart/patrepeval huggingface dataset:
CEP-32496: A Novel Orally Active BRAFV600E Inhibitor with Selective Cellular and In Vivo Antitumor Activity (2012)

Mutations in the BRAF gene have been identified in approximately 7% of cancers, including 60% to 70% of melanomas, 29% to 83% of papillary thyroid carcinomas, 4% to 16% colorectal cancers, and a lesser extent in serous ovarian and non-small cell lung cancers. The V600E mutation is found in the vast majority of cases and is an activating mutation, conferring transforming and immortalization potential to cells. CEP-32496 is a potent BRAF inhibitor in an in vitro binding assay for mutated BRAF(V600E) (K(d) BRAF(V600E) = 14 nmol/L) and in a mitogen-activated protein (MAP)/extracellular signal-regulated (ER) kinase (MEK) phosphorylation (pMEK) inhibition assay in human melanoma (A375) and colorectal cancer (Colo-205) cell lines (IC(50) = 78 and 60 nmol/L). In vitro, CEP-32496 has multikinase binding activity at other cancer targets of interest; however, it exhibits selective cellular cytotoxicity for BRAF(V600E) versus wild-type cells. CEP-32496 is orally bioavailable in multiple preclinical species (>95% in rats, dogs, and monkeys) and has single oral dose pharmacodynamic inhibition (10-55 mg/kg) of both pMEK and pERK in BRAF(V600E) colon carcinoma xenografts in nude mice. Sustained tumor stasis and regressions are observed with oral administration (30-100 mg/kg twice daily) against BRAF(V600E) melanoma and colon carcinoma xenografts, with no adverse effects. Little or no epithelial hyperplasia was observed in rodents and primates with prolonged oral administration and sustained exposure. CEP-32496 benchmarks favorably with respect to other kinase inhibitors, including RAF-265 (phase I), sorafenib, (approved), and vemurafenib (PLX4032/RG7204, approved). CEP-32496 represents a novel and pharmacologically active BRAF inhibitor with a favorable side effect profile currently in clinical development.
Discovery, mode of action, resistance mechanisms, and plan of action for sustainable use of Group 14 herbicides (2023)

Abstract Protoporphyrinogen oxidase (PPO)-inhibiting herbicides remain an important and useful chemistry 60 yr after their first introduction. In this review, based on topics introduced at the Weed Science Society of America 2021 symposium titled “A History, Overview, and Plan of Action on PPO Inhibiting Herbicides,” we discuss the current state of PPO-inhibiting herbicides. Renewed interest in the PPO-inhibiting herbicides in recent years, due to increased use and increased cases of resistance, has led to refinements in knowledge regarding the mechanism of action of PPO inhibitors. Herein we discuss the importance of the two isoforms of PPO in plants, compile a current knowledge of target-site resistance mechanisms, examine non–target site resistance cases, and review crop selectivity mechanisms. Consistent and reproducible greenhouse screening and target-site mutation assays are necessary to effectively study and compare PPO-inhibitor resistance cases. To this end, we cover best practices in screening to accurately identify resistance ratios and properly interpret common screens for point mutations. The future of effective and sustainable PPO-inhibitor use relies on development of new chemistries that maintain activity on resistant biotypes and the promotion of responsible stewardship of PPO inhibitors both new and old. We present the biorational design of the new PPO inhibitor trifludimoxazin to highlight the future of PPO-inhibitor development and discuss the elements of sustainable weed control programs using PPO inhibitors, as well as how responsible stewardship can be incentivized. The sustained use of PPO inhibitors in future agriculture relies on the effective and timely communication from mode of action and resistance research to agronomists, Extension workers, and farmers.
Optical 3D measurement of objects with technical surfaces (1996)

The digitalization of CAD-models, the complete manufacturing control and the timely quality control of components are important tasks of modern industrial inspection. In many cases the 3D-object shape as well as its deviation from a certain master object is of special interest, whereas optical measuring techniques based on structured light find increasing application /1 - 4/. Unfortunately, as a rule the application of these optical 3D-inspection systems leads to difficulties if the surfaces under test are strongly structured yielding to a shadowing within the image field. Moreover, distortions appear if the detector records too high light intensities in some ranges of the image caused by light reflection and diffraction at the surface of the object. So, within these ranges of the image one could not get useful values of measurement of the coordinates. The method of structured illumination allows the development of a concept of measurement which can avoid these illumination-caused difficulties.
Increased expression of inducible HSP70 in apoptotic cells is correlated with their efficacy for antitumor vaccine therapy (2004)

Apoptosis is a physiologic process in normal development, tissue remodeling and cell turnover. This cell death is noninflammatory and nonimmunogenic, but when associated with a danger signal, it can activate the immune system. However, the capacity of apoptotic cells to activate the immune system is not clearly established, although dead tumor cells have been largely exploited as a source of TAA in cellular therapy against cancer. From these cellular preparations, contradictory results have been reported on the effect of apoptotic cells as an effective source of TAA and their immunologic properties. These conflicting data strongly suggest that the optimal preparation of apoptotic cells derived from tumor cells remains to be determined. In this work, we studied and compared the efficacy of antitumor immune responses derived from repeated injections using different preparations of apoptotic cells. We investigated the importance of HSP70 and TGF-beta expression in apoptotic cells used in the treatment of an established and nonimmunogenic rat carcinoma. UVB-mediated apoptosis did not affect TGF-beta expression in tumor cells, whereas HS treatment sharply downregulated it. Thus, downregulation of TGF-beta permits normal DC activation and maturation and the induction of tumor immunity. We conclude that HS followed by UVB irradiation is a superior source of tumor antigen for the treatment of established tumors. Future work will determine whether HS independently upregulates HSP70, thereby suppressing expression of active TGF-beta, or whether the 2 are linked via a still undefined mechanism.
The Fcγ Receptor Genotype as a Severity Factor for Chronic Periodontitis in Japanese Patients (2001)

Our results document the Fc gamma RIIIa-158V allele and possibly Fc gamma RIIIb-NA2 to be associated with severity of CP in Japanese patients.
WFMS: The Next Generation of Distributed Processing Tools. (1997)

There was no clinically significant voice change after oral topical anesthesia.
Who is Listening? Security in Wireless Networks (2008)

Wireless networks have significantly impacted the world as far back as World War II. Through the use of wireless networks, information could be sent overseas or behind enemy lines easily and quickly. Since then wireless networks have continued to develop and its uses have significantly grown. This rapid proliferation of wireless networks has been closely accompanied by an increasing number of security threats. This paper describes an overview of security issues in wireless networks. Security issues in wireless networks span multiple layers including physical layer, network layer and application layer and encompass cross-layer attacks based on identity management and side channels. This paper discusses some prominent security issues in the context of wireless networks and presents qualitative arguments that demonstrate the infeasibility of building unbreakable security mechanisms under a bounded resource model. Hence, it is becomes crucial to identify trade-offs between attack and defense strategies and their cost structures (such as performance overhead). The paper concludes with a discussion on an emerging paradigm for achieving a quantifiable level of security using a risk analysis approach that captures the notion of risk and pricing.
A CD-R System for Recording Computer-Generated Holograms (2004)

To display 3D images on a computer-generated hologram, you need to have a very high resolution hologram-recording system. We developed a CD-R (Compact Disk-Recordable) drive to record CGH data on CD-R disks, that have a high resolution and a dot size of 1.5μm. By using this drive, it is possible to make holograms inexpensively in a short-time without the need for special environments, such as dark rooms, clean rooms, etc. The drive realizes desktop holograming that can handle all CGH process including model making, hologram calculations, and hologram recordings on a personal computer. In this paper, we describe the system and discuss the hologram-calculation method adapted for CD-R disks.
Potential for reducing the numbers of SiPM readout surfaces of laser-processed X’tal cube PET detectors (2013)

We are developing a three-dimensional (3D) position-sensitive detector with isotropic spatial resolution, the X'tal cube. Originally, our design consisted of a crystal block for which all six surfaces were covered with arrays of multi-pixel photon counters (MPPCs). In this paper, we examined the feasibility of reducing the number of surfaces on which a MPPC array must be connected with the aim of reducing the complexity of the system. We evaluated two kinds of laser-processed X'tal cubes of 3 mm and 2 mm pitch segments while varying the numbers of the 4 × 4 MPPC arrays down to two surfaces. The sub-surface laser engraving technique was used to fabricate 3D grids into a monolithic crystal block. The 3D flood histograms were obtained by the Anger-type calculation. Two figures of merit, peak-to-valley ratios and distance-to-width ratios, were used to evaluate crystal identification performance. Clear separation was obtained even in the 2-surface configuration for the 3 mm X'tal cube, and the average peak-to-valley ratios and the distance-to-width ratios were 6.7 and 2.6, respectively. Meanwhile, in the 2 mm X'tal cube, the 6-surface configuration could separate all crystals and even the 2-surface case could also, but the flood histograms were relatively shrunk in the 2-surface case, especially on planes parallel to the sensitive surfaces. However, the minimum peak-to-valley ratio did not fall below 3.9. We concluded that reducing the numbers of MPPC readout surfaces was feasible for both the 3 mm and the 2 mm X'tal cubes.
Abiotic aspects of channels and floodplains in riparian ecology (1998)

Summary 1. The ecology of riparian zones is enormously influenced by the heterogeneous sedimentary structures and associated complex hydrologic flow paths that mediate surface‐ and groundwater exchanges. Sedimentary structures form a three‐dimensional, dynamic framework that controls subsurface flow and the vertical and horizontal exchange of water between channels and floodplains in gravel bed rivers. The modern structure of the bed sediments reflects the legacy of cut and fill alluviation for a particular river basin. 2. Highly permeable sedimentary textures, particularly open framework gravels, allow rapid exchange between surface and groundwaters. 3. Ground penetrating radar provides high resolution information on the nature and three‐dimensional distribution of the sediments within the shallow subsurface (4–25 m) of gravel bed rivers. Bed sediments can be mapped at the decimeter scale. 4. Exchange and mixing of ground and channel water occurs along losing, gaining and flow‐through reaches as determined by the hydraulic gradient and transmissivity of the bed sediments. 5. Spatial and temporal patterns of surface‐ and groundwater interactions can be quantified by mass flux measurements and by assessing geochemical contrasts. Natural tracers, such as temperature or radon, are well suited for mapping exchange sites and quantifying interactions. Artificial signals produced by injecting anions, like chloride, bromide and organic dyes are also useful. 6. The study of riparian ecosystems requires an understanding of the geomorphic structures and processes that build and maintain bed sediments and flow pathways through them.
Evaluation of curcumin and copper acetate against Salmonella Typhimurium infection, intestinal permeability, and cecal microbiota composition in broiler chickens (2020)

Abstract Background: Interest in the use of natural feed additives as an alternative to antimicrobials in the poultry industry has increased in recent years because of the risk of bacterial resistance. One of the most studied groups are polyphenolic compounds, given their advantages over other types of additives and their easy potentiation of effects when complexes are formed with metal ions. Therefore, the objective of the present study was to evaluate the impact of dietary supplementation of copper acetate (CA), curcumin (CR), and their combination (CA-CR) against Salmonella Typhimurium colonization, intestinal permeability, and cecal microbiota composition in broiler chickens through a laboratory Salmonella infection model. S. Typhimurium recovery was determined on day 10 post-challenge by isolating Salmonella in homogenates of the right cecal tonsil (12 chickens per group) on Xylose Lysine Tergitol-4 (XLT-4) with novobiocin and nalidixic acid. Intestinal integrity was indirectly determined by the fluorometric measurement of fluorescein isothiocyanate dextran (FITC-d) in serum samples from blood obtained on day 10 post- S. Typhimurium challenge. Finally, microbiota analysis was performed using the content of the left caecal tonsil of 5 chickens per group by sequencing V4 region of 16S rRNA gene. Results: The results showed that in two independent studies, all experimental treatments were able to significantly reduce the S . Typhimurium colonization in cecal tonsils (CT, P &lt; 0.0001) compared to the positive control (PC) group. However, only CA-CR was the most effective treatment in reducing S . Typhimurium counts in both independent studies. Furthermore, the serum fluorescein isothiocyanate dextran (FITC-d) concentration in chickens treated with CR was significantly lower when compared to PC ( P = 0.0084), which is related to a decrease in intestinal permeability and therefore intestinal integrity. The effect of dietary treatments in reducing Salmonella was further supported by the analysis of 16S rRNA gene sequences using Linear discriminant analysis effect size (LEfSe) since Salmonella was significantly enriched in PC group (LDA score &gt; 2.0 and P &lt;0.05) compared to the other groups. In addition, Coprobacillus , Eubacterium , and Clostridium were significantly higher in the PC group compared to other treatment groups. On the contrary, Fecalibacterium and Enterococcus in CR, unknown genus of Erysipelotrichaceae at CA-CR, and unknown genus of Lachnospiraceae at CA were significantly more abundant respectively. Conclusions: CR treatment was the most effective treatment to reduce S . Typhimurium intestinal colonization and maintain better intestinal homeostasis which might be achieved through modulation of cecal microbiota.
Performance of the missing transverse energy reconstruction by the CMS experiment in sqrt(s) = 8 TeV pp data (2014)

The performance of missing transverse energy reconstruction algorithms is presented using √s=8 TeV proton-proton (pp) data collected with the CMS detector. Events with anomalous missing transverse energy are studied, and the performance of algorithms used to identify and remove these events is presented. The scale and resolution for missing transverse energy, including the effects of multiple pp interactions (pileup), are measured using events with an identified Z boson or isolated photon, and are found to be well described by the simulation. Novel missing transverse energy reconstruction algorithms developed specifically to mitigate the effects of large numbers of pileup interactions on the missing transverse energy resolution are presented. These algorithms significantly reduce the dependence of the missing transverse energy resolution on pileup interactions. Finally, an algorithm that provides an estimate of the significance of the missing transverse energy is presented, which is used to estimate the compatibility of the reconstructed missing transverse energy with a zero nominal value.
Improvement of polysilicon oxide characteristics by fluorine incorporation (1994)

The effect of fluorine on the polysilicon oxide (polyoxide) characteristics is investigated. It is found that the polyoxide leakage current and breakdown strength are improved as fluorine is incorporated into the oxide film. Experimental results show that the improvement is believed to be due to the oxide stress relaxation rather than the change of the polyoxide/polysilicon interface texture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis of the ruthenium imido complexes, [Ru(η-C6H6)(N-2,6-R2C6H3)]2(R = Prior Me), and the crystal structure of [Ru(η-C6H6)(N-2,6-Pri2C6H3)]2 (1991)

Ruthenium imido complexes, [(η-C6H6)Ru(N-2,6-R2C6H3)]2(R = Pri1, Me 2), have been synthesised by the room temperature reaction of [(η-C6H6)RuCl2]2 with 2 equiv. of LiNH(2,6-R2C6H3) and 1 has been shown by single-crystal X-ray diffraction to be a symmetrical, imido-bridged dimer containing a bent Ru2N2 bridge.
See-through amorphous silicon solar cells with selectively transparent and conducting photonic crystal back reflectors for building integrated photovoltaics (2013)

Thin semi-transparent hydrogenated amorphous silicon (a-Si:H) solar cells with selectively transparent and conducting photonic crystal (STCPC) back-reflectors are demonstrated. Short circuit current density of a 135 nm thick a-Si:H cell with a given STCPC back-reflector is enhanced by as much as 23% in comparison to a reference cell with an ITO film functioning as its rear contact. Concurrently, solar irradiance of 295 W/m2 and illuminance of 3480 lux are transmitted through the cell with a given STCPC back reflector under AM1.5 Global tilt illumination, indicating its utility as a source of space heating and lighting, respectively, in building integrated photovoltaic applications.
Resistance of insect pests to neonicotinoid insecticides: Current status and future prospects (2005)

The first neonicotinoid insecticide introduced to the market was imidacloprid in 1991 followed by several others belonging to the same chemical class and with the same mode of action. The development of neonicotinoid insecticides has provided growers with invaluable new tools for managing some of the world's most destructive crop pests, primarily those of the order Hemiptera (aphids, whiteflies, and planthoppers) and Coleoptera (beetles), including species with a long history of resistance to earlier-used products. To date, neonicotinoids have proved relatively resilient to the development of resistance, especially when considering aphids such as Myzus persicae and Phorodon humuli. Although the susceptibility of M. persicae may vary up to 20-fold between populations, this does not appear to compromise the field performance of neonicotinoids. Stronger resistance has been confirmed in some populations of the whitefly, Bemisia tabaci, and the Colorado potato beetle, Leptinotarsa decemlineata. Resistance in B- and Q-type B. tabaci appears to be linked to enhanced oxidative detoxification of neonicotinoids due to overexpression of monooxygenases. No evidence for target-site resistance has been found in whiteflies, whereas the possibility of target-site resistance in L. decemlineata is being investigated further. Strategies to combat neonicotinoid resistance must take account of the cross-resistance characteristics of these mechanisms, the ecology of target pests on different host plants, and the implications of increasing diversification of the neonicotinoid market due to a continuing introduction of new molecules.
High-temperature polarization analysis of polyethylene and polyethylene-semicon bilayers (2022)

Crosslinked polyethylene (XLPE) is a key material for power cable insulation due to its superior electrical properties. It is co-extruded with a semiconducting “semicon” layer, which is significantly more conductive than XLPE due to the incorporation of carbon black. Understanding the electrical properties of the XLPE/semicon bilayer and the interface between them is critical due to their common use. Two techniques were used to study electrical properties of XLPE and XLPE/semicon bilayers. One was current-voltage measurements, which analyzed resistivity as a function of time. The other was high-voltage polarization, which analyzed polarizability and dielectric loss as a function of electrical field. Thin films of PE and semicon were made via melt pressing. Dicumyl peroxide was infused to the beads prior to melt pressing such that XLPE was formed. All samples were degassed to remove DCP byproducts. Semicon/polyethylene bilayers were made by pressing the two layers together. LDPE and LDPE/semicon were also studied. Bulk brass electrodes were used. Current-voltage measurements showed that adding the semicon layer increased conductivity by an order of magnitude. Polarization measurements revealed that significant enhancement in the dielectric loss occurred at electric fields of 15 kV/mm and above. Polyethylene by itself and semicon bilayer samples had distinct electrical properties, and thus a proper understanding of the performance of XLPE in power cables required analyzing both. Further work is suggested that focuses on correlating changes in measured conductivity to the nature of the material interface (e.g., via enhanced charge injection and/or introduction of charge carriers).
Question Answering from Unstructured Text by Retrieval and Comprehension (2017)

Open domain Question Answering (QA) systems must interact with external knowledge sources, such as web pages, to find relevant information. Information sources like Wikipedia, however, are not well structured and difficult to utilize in comparison with Knowledge Bases (KBs). In this work we present a two-step approach to question answering from unstructured text, consisting of a retrieval step and a comprehension step. For comprehension, we present an RNN based attention model with a novel mixture mechanism for selecting answers from either retrieved articles or a fixed vocabulary. For retrieval we introduce a hand-crafted model and a neural model for ranking relevant articles. We achieve state-of-the-art performance on W IKI M OVIES dataset, reducing the error by 40%. Our experimental results further demonstrate the importance of each of the introduced components.
Molecular Inhibition for Selective CO2 Conversion (2022)

Abstract Electrochemical CO 2 reduction presents a sustainable route to the production of chemicals and fuels. Achieving a narrow product distribution with heterogeneous Cu catalysts is challenging and conventional material modifications offer limited control over selectivity. Here, we show that surface‐immobilised molecular species can act as inhibitors for specific carbon products to provide rational control over product distributions. Combined experimental and computational results showed that anchoring of a thiol‐functionalised pyridine on Cu destabilises a surface‐bound reaction intermediate to energetically block a CO‐producing pathway, thereby favouring formate production. The nitrogen atom was shown to be essential to the inhibition mechanism. The ability of molecules to control selectivity through inhibition of specific reaction pathways offers a unique approach to rationally modify heterogeneous catalysts.
Oxysterol-binding protein-1 (OSBP1) modulates processing and trafficking of the amyloid precursor protein (2008)

These results suggest that OSBP1 could play a role in linking cholesterol metabolism with intracellular APP trafficking and Abeta production, and more importantly indicate that OSBP1 could provide an alternative target for Abeta-directed therapeutic.