gebhart/patrepeval huggingface dataset:
Genetic and Pharmacological Screens Converge in Identifying FLIP, BCL2, and IAP Proteins as Key Regulators of Sensitivity to the TRAIL-Inducing Anticancer Agent ONC201/TIC10 (2015)

ONC201/TIC10 is a small-molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway-inducer KSR1. Unexpectedly, KSR1 silencing did not affect MAPK signaling in the presence or absence of ONC201, but instead reduced expression of the antiapoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin. In parallel to this work, we also conducted a synergy screen in which ONC201 was combined with approved small-molecule anticancer drugs. In multiple cancer cell populations, ONC201 synergized with diverse drug classes, including the multikinase inhibitor sorafenib. Notably, combining ONC201 and sorafenib led to synergistic induction of TRAIL and its receptor DR5 along with a potent induction of cell death. In a mouse xenograft model of hepatocellular carcinoma, we demonstrated that ONC201 and sorafenib cooperatively and safely triggered tumor regressions. Overall, our results established a set of determinants for ONC201 sensitivity that may predict therapeutic response, particularly in settings of sorafenib cotreatment to enhance anticancer responses.
Negligible nonlinear absorption in hydrogenated amorphous silicon at 155μm for ultra-fast nonlinear signal processing (2014)

Three-photon absorption (3PA) has been observed as the dominant mechanism for nonlinear absorption in wide-bandgap hydrogenated amorphous silicon (a-Si:H-W) at 1.55 μm. The nonlinear index n2 and 3PA coefficient were measured to be 22 × 10(-17)m(2)/W and 5.0 × 10(-26) m(3)/W(2) respectively at 1.55 μm by using the z-scan method. This indicates that the figure of merit (FOM) of this material is intensity dependent. A value FOM>60 is predicted at intensities below 0.5 GW/cm(2) which is the maximum practical intensity for high-bit-rate (>160 GB/s) alloptical signal processing. The nonlinear phase change in a-Si:H-W has been compared with other common nonlinear materials (c-Si, As(2)S(3), Ge(11.5)As(24)Se(64.5)) for a 2 cm long waveguide with a-Si:H-W showing the greatest potential for integrated devices for all-optical processing with a high nonlinear index and negligible nonlinear absorption at intensities < 0.5 GW/cm(2).
The significance of EGFR pathway mutations for the efficacy of first line treatment with bevacizumab in metastatic colonrectal cancer. (2015)

699 Background: After analysis of minor RAS mutations (KRAS exon3, 4/NRAS) in FIRE-3 or PRIME study, so called all RAS mutation would be being regarded as a biomarker for anti-EGFR antibodies. BRAF and PIK3CA mutation would be a candidate of biomarkers for anti EGFR targeted therapies. However it remains unknown whether EGFR pathway mutations affect the efficacy of bevacizumab in Stage.‡W CRC. Methods: Of the 1,001 consecutive patients of CRC in our institute between Nov 2006 and Dec 2013, we examined RAS, PIK3CA and BRAF mutational status, 141 patients received systemic chemotherapy for the first line treatment of Stage.‡W. Among them, 96 patients were administered chemotherapy with bevacizumab. Overall survival (OS), Time to Treatment Failure (TTF) and Objective Response Rate (ORR) were evaluated by mutational status. Results: Baseline characteristics were as follows (n=141): median age, 63; male/female, 80/61; ECOG PS 0-1/2, 135/4; chemotherapy with bevacizumab/chemotherapy with anti-EGFR antibodies/cytotoxic agent alone, 96/22/23;KRAS (codon 12,13) wild-type (WT)/RAS wild-type(WT), 89/80; PIK3CA mutation (exon 9/exon 20)/BRAF mutation, 11(5/6)/13. Median OS and TTF were 32.1 and 8.0 months respectively. In chemotherapy with bevacizumab, ORRs were 46.3% (all cases), 55.3% (KRAS WT), 54.5% (RAS WT) and 60.6% (all WT) respectively. ORR was gradually improved by focusing therapeutic target on all wild population. However, there were no significant differences in TTF and OS among them. PIK3CA mutation had a trend toward shorter TTF of bevacizumab (p=0.056). This trend was observed in PIK3CA mutation on exon 20 but not observed exon 9. BRAF mutation had significantly associated with poor OS not only for bevacizumab cases but also all therapies. Conclusions: In our study, profiling of EGFR pathway mutations may not contribute to enrich patients with benefit from chemotherapy with bevacizumab.
RUBreathing (2015)

The respiration rate of a person provides critical information about their well-being. Conventionally, contact sensing is used for breathing monitoring; however, it is expensive, uncomfortable, and immobile. In-home non-contact breathing monitoring is now possible via Doppler radar and motion capture video sensors, yet these technologies are limited in mobility, among other limitations. When monitoring a patient who is free to move around his or her home, it is dificult to scale current non-contact sensors to cover the large area. Our RUBreathing sensor system uses RF received signal strength (RSS) in a network to estimate breathing rate in real-time with high accuracy over a wide area. In this demonstration, we show the sensor continuously estimating a patient's respiration rate from non-contact RSS measurements between wireless devices.
Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin α1 (2010)

Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin α1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved the crystal structures of CENTA1 in ligand-free, KIF13B-FHA domain-bound, and PIP3 head group (IP4)-bound conformations, and the CENTA1/KIF13B-FHA/IP4 ternary complex. The first pleckstrin homology (PH) domain of CENTA1 specifically binds to PIP3, while the second binds to both PIP3 and phosphatidylinositol 3,4-biphosphate (PI(3,4)P(2)). The FHA domain of KIF13B interacts with the PH1 domain of one CENTA1 molecule and the ArfGAP domain of a second CENTA1 molecule in a threonine phosphorylation-independent fashion. We propose that full-length KIF13B and CENTA1 form heterotetramers that can bind four phosphoinositide molecules in the vesicle and transport it along the microtubule.
Antigen Retrieval for Immunohistochemical Reactions in Routinely Processed Paraffin Sections (2003)

Immunohistochemistry is an essential adjunct of modern diagnostic pathology. In the majority of cases, pathological tissue samples are fixed in formal dehyde and embedded in paraffin wax for examination of microscopic morphology. A major limitation of routinely processed tissues for immunohistochemistry is that many potentially interesting antigens are altered during tissue fixation and processing. As an alternative, sections of snap-frozen tissues can be used to detect most of these antigens. Nevertheless, paraffin sections offer well-preserved tissue architecture and cytomorphology superior to that obtained in frozen sections and thus allow more accurate antigen localization. Furthermore, paraffin-embedded tissues represent an invaluable source of human tissues, easily accessible for retrospective studies back decades. Thus, for diagnostic and research purposes, paraffin sections are preferred for immunohistochemical analysis by most laboratories.
A Two-Stage Three-Phase Integrated Charger for Electric Vehicles With Dual Cascaded Control Strategy (2018)

A new three-phase integrated onboard charger and derivative control strategy are proposed and implemented in this paper. The integrated charger is composed of a three-phase interface and the traction propulsion system of the vehicle. The three-phase interface is derived based on the traditional three-phase three-switch buck ac-dc converter and is integrated with the propulsion system to construct an integrated buck-boost charger, in which the inverter is reconfigured to operate as an interleaved converter. The motor windings are used as the inductors of the integrated buck-boost charger. A dual cascaded control strategy is designed for the two-stage charger. The first cascaded control regulates the battery voltage and the motor-winding currents, while the second cascaded control modulates the input filter inductor current and the input filter capacitor voltage. The integrated charger is modeled and analyzed to design the controllers, considering the sensitivities of duty cycle to the input filter inductor current and to the input filter capacitor voltage, and the sensitivity of the modulation index to the motor-winding currents. A 1.5-kW prototype is designed and developed to verify the feasibility of the proposed integrated charger and the control strategy.
Electronic transport in field-effect transistors of sexithiophene (2004)

The electronic conduction of thin-film field-effect-transistors (FETs) of sexithiophene was studied. In most cases the transfer curves deviate from standard FET theory; they are not linear, but follow a power law instead. These results are compared to conduction models of “variable-range hopping” and “multi-trap-and-release”. The accompanying IV curves follow a Poole-Frenkel (exponential) dependence on the drain voltage. The results are explained assuming a huge density of traps. Below 200 K, the activation energy for conduction was found to be ca. 0.17 eV. The activation energies of the mobility follow the Meyer-Neldel rule. A sharp transition is seen in the behavior of the devices at around 200 K. The difference in behavior of a micro-FET and a submicron FET is shown.
Evaluating the FOKS Error Model (2004)

Learners of Japanese face great difficulty when trying to lookup words containing kanji in a dictionary, due to the requirement of knowing the correct reading of the target word. We propose a system that imitates the cognitive process learners go through in generating readings for novel kanji strings, and provide direct access to the dictionary entries based on the generated readings. In doing so we remove the correct reading requirement. The system described here is implemented in a web-based environment and freely available for general use. In this paper we provide an analysis of query and error data collected by our server. 1.
The Effect of Predisinfection with Chlorine Dioxide on the Formation of Haloacetic Acids and Trihalomethanes in a Drinking Water Supply (2001)

In an effort to maintain compliance with current and future United States Environmental Protection Agency regulations governing haloacetic acids (HAAs) and trihalomethanes (THMs), the Blacksburg, Christiansburg, VPI (BCVPI) Water Authority in Radford, Virginia elected to eliminate prechlorination and replace it with preoxidation using chlorine dioxide (ClO2). Prior to full-scale application at the BCVPI Water Treatment Plant, jar testing was done to determine the effects of ClO2 on the formation of HAAs and THMs. Jar testing results showed a significant reduction in THM formation potential when 2.0 mg/L ClO2 was applied to raw water and chlorination was delayed. Chlorine dioxide doses less than 2.0 mg/L were statistically insignificant in the reduction of THM formation potentials below samples that were prechlorinated according to the BCVPI Water Treatment Plants current practice. Likewise, ClO2 did not alter HAA formation potentials in such a way that statistical differences could be detected between ClO2 pretreatment and prechlorination, even at a dose of 2.0 mg/L ClO2. The two inorganic byproducts of ClO2, chlorite and chlorate, were also measured following jar tests. Chlorite concentrations increased with an increased ClO2 dose, but remained below 1.0 mg/L. Chlorate was formed in all jar-test samples. iii
Action as an innate bias for visual learning (2012)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Prove-It: A Proof Assistant for Organizing and Verifying General\n Mathematical Knowledge (2020)

We introduce Prove-It, a Python-based general-purpose interactive\ntheorem-proving assistant designed with the goal of making formal theorem\nproving as easy and natural as informal theorem proving (with moderate\ntraining). Prove-It uses a highly-flexible Jupyter notebook-based user\ninterface that documents interactions and proof steps using LaTeX. We review\nProve-It's highly expressive representation of expressions, judgments,\ntheorems, and proofs; demonstrate the system by constructing a traditional\nproof-by-contradiction that $\\sqrt{2}\\notin\\mathbb{Q}$; and discuss how the\nsystem avoids inconsistencies such as Russell's and Curry's paradoxes.\nExtensive documentation is provided in the appendices about core elements of\nthe system. Current development and future work includes promising applications\nto quantum circuit manipulation and quantum algorithm verification.\n
Lung Deposition of Formoterol HFA (Atimos ® /Forair ® ) in Healthy Volunteers, Asthmatic and COPD Patients (2007)

In this study, the influence of lung function on lung deposition of a radioactively labeled Formotoerol HFA MDI (Forair) was investigated. Eighteen subjects were measured: 6 healthy subjects (FEV(1) = 107% pred), 6 patients with Asthma (FEV(1) = 72% pred), and 6 patients with COPD (FEV(1) = 40% pred). The lung deposition of the radioactive-labeled drug was measured with a gamma camera. The lung deposition relative to the emitted dose was 31% for healthy subjects, 34% for asthmatics, and 35% for COPD patients. These data suggest a comparable lung deposition in the different populations. There was no significant correlation between lung function (FEV(1)) and lung deposition. The extrathoracic deposition was around 50%. The finding were that lung deposition of the inhaled Formoterol did not depend on lung function and the relative high values of lung deposition can be explained by the small particle size (0.8 microm) of the HFA-Formoterol-Formulation and the slow inhalation (30 L/min flow) used in this study. It can be concluded, that with this modern HFA drug formulation, the deposition is high, even in obstructed lungs.
A Metalens Array on a 12-inch Glass Wafer for Optical Dot Projection (2020)

We report the first demonstration of a metalens array fabricated on a 12-inch glass wafer for dot projection. Good uniformity in dot size is achieved, with a maximum deviation of 8% to the simulated value.
The Social and External Benefits of Education (2004)

This major Handbook comprehensively surveys the rapidly growing field of the economics of education. It is unique in that it comprises original contributions on an exceptional range of topics from a review of human capital, signalling and screening models, to consideration of issues such as educational externalities and economic growth, funding models, determinants of educational success, the educational production function, educational standards and efficiency measurement. Labour market issues such as the market for teachers and the transition of students from school to work are also explored.
Increased plant quality and water savings in Pelargonium × hortorum in response to reduced irrigation frequency (2017)

Limiting irrigation frequency may present an alternative approach to conventional irrigation practices, leading to water savings whilst maintaining crop yield and/or quality.This may be particularly relevant in commercial nurseries with appropriate irrigation technology.Pelargonium x hortorum Bullseye Cherry plants were grown under glasshouse conditions under either well-watered (WW; daily replacement of 100% of evapotranspiration (ET)), frequent (FDI), or infrequent (IDI) deficit irrigation regimes (50% of ET supplied daily or cumulatively every 4 days, respectively) for 24 days.Stomatal conductance (gs) and leaf water potential (Ψleaf) were measured as indicators of plant water relations.Plant quality was determined by canopy volume.Water use efficiency (WUE) was established as the ratio of shoot dry biomass to total water applied.Both FDI and IDI decreased gs but there were treatment differences in Ψleaf.FDI resulted in a more positive Ψleaf, whilst IDI decreased Ψleaf over the experimental period.Deficit irrigation frequency had no effect on either plant volume or biomass during the initial 12 days of the experiment, although by Day 24, both IDI and FDI were significantly lower than WW plants (albeit FDI plants had a greater biomass than IDI plants).This corresponded with IDI and FDI showing a higher WUE than WW plants during the first half of the experiment, but this effect was diminished as growth decreased under both deficit irrigation treatments.During deficit irrigation, irrigation frequency had two main effects on P.hortorum.FDI prevents the onset of leaf water deficit and partially maintains biomass accumulation.However, IDI reduces growth compared to FDI and produces more compact plants, thereby increasing ornamental quality, whilst also enhancing WUE during the early stages of the experiment.This suggests that irrigation frequency can be altered to deliver specific grower objectives.
Large-area molecular junctions (2007)

Although still a relatively new field, molecular electronics can be regarded as the next evolutionary stage for plastic electronics. Molecular electronics holds the potential to fabricate elements for electronics circuits with a functionality that is embedded in just a single layer of molecules. Instead of using photolithography or printing techniques to etch or print nano-scale circuit features, molecular electronics can be engineered to use organic molecules that spontaneously form the correct structures via self-organization. Especially the theoretical prediction of unipolar rectifiers has led to a worldwide effort on the experimental verification. Transport through single molecules has been investigated by scanning probes, break-junctions and metallic cross bar devices. Molecular devices have been reported showing intriguing phenomena as rectification, negative differential resistances, stochastic switching, the Kondo-effect and conductance switching. The reproducibility however, is doubtful. Rectification is due to contacts and not related to the functionality of the molecule; negative differential resistances appear to be due to irreversible electrochemical reactions and stochastic switching due to molecular diffusion. Progress in the field of molecular electronics is hampered by the lack of reliable and reproducible data. In this presentation we will present a novel technology to fabricate in high yield large-area metal/self-assembled monolayer/metal junctions. The technology is based on the use of a conducting barrier in between the monolayer and the top metal to prevent the formation of shorts, and on processing junctions in photolithographically defined via holes to prevent cross talk. The technology is optimized for alkane(di)thiols to benchmark the electrical transport.
Hyperpiliation reduces Pseudomonas aeruginosa pathogenicity by impeding type III secretion (2021)

ABSTRACT Type IVa pili (T4aP) are important virulence factors for many bacterial pathogens. Previous studies suggested that the retraction ATPase, PilT, modulates pathogenicity due to its critical role in pilus dynamics and twitching motility. Here we use a Caenorhabditis elegans slow killing model to show that hyperpiliation, not loss of pilus retraction, reduces virulence of Pseudomonas aeruginosa strains PAK and PA14 by interfering with function of the contact-dependent type III secretion system (T3SS). Hyperactivating point mutations in the P. aeruginosa PilSR two-component system that controls transcription of the major pilin gene, pilA , increased levels of surface pili to the same extent as deleting pilT , without impairing twitching motility. These functionally hyperpiliated PilSR mutants had significant defects in pathogenicity that were rescued by deleting pilA or by increasing the length of T3SS needles via deletion of the needle-length regulator, PscP. Hyperpiliated pilT deletion or pilO point mutants showed similar PilA-dependent impairments in virulence, validating the phenotype. Together, our data support a model where a surfeit of pili prevents effective engagement of contact-dependent virulence factors. These findings suggest that the role of T4aP retraction in virulence should be revised. SIGNIFICANCE Pseudomonas aeruginosa is a major contributor to hospital-acquired infections and particularly problematic due to its intrinsic resistance to many front-line antibiotics. Strategies to combat this and other important pathogens include development of anti-virulence therapeutics. We show that the pathogenicity of P. aeruginosa is impaired when the amount of type IVa pili (T4aP) expressed on the cell surface increases, independent of the bacteria’s ability to twitch. We propose that having excess T4aP on the cell surface can physically interfere with productive engagement of the contact-dependent type III secretion toxin delivery system. A better understanding of how T4aP modulate interaction of bacteria with target cells will improve the design of therapeutics targeting components involved in regulation of T4aP expression and function, to reduce the clinical burden of P. aeruginosa and other T4aP-expressing bacteria.
Reactive Discovery of Point-to-Point Routes in Low-Power and Lossy Networks (2013)

This document specifies a point-to-point route discovery mechanism, complementary to the Routing Protocol for Low-power and Lossy Networks (RPL) core functionality. This mechanism allows an IPv6 router to discover "on demand" routes to one or more IPv6 routers in a Low-power and Lossy Network (LLN) such that the discovered routes meet specified metrics constraints.
The operative treatment of full thickness cartilage defects in the knee joint with autologous chondrocyte transplantation. (2000)

Autologous chondrocyte transplantation has to be considered a safe and effective method for the treatment of large full thickness cartilage defects. Alternative treatments are symptomatical: drilling, abrasion, lavage, chondroplasty, or osteotomies. The short term results are promising but a lot of patients have to be treated for osteoarthritis as a consequence of failure with total joint arthroplasty. Osteochondral transplantations have the disadvantage of limited harvesting sites and the impairment of the subchondral bone plate.
ChemInform Abstract: HIGHLY REDUCED ORGANOMETALLICS. 15. COORDINATIVELY UNSATURATED TETRANUCLEAR HYDRIDO CARBONYL CLUSTERS OF MOLYBDENUM AND TUNGSTEN. STRUCTURAL CHARACTERIZATION OF TETRAKIS(TETRAPROPYLAMMONIUM) TETRAKIS(TRICARBONYLHYDROMOLYBDATE) (((N‐C3H7)4N)4(HMO(CO)3)4) (1984)

Abstract Behandelt man die Komplexe (I) mit dem Borat (II) in THF, so werden nach anschließendem Kationenaustausch die vierkernigen Hydridocarbonylcluster (III) erhalten.