gebhart/patrepeval huggingface dataset:
The anti–PD-1 antibody spartalizumab in combination with dabrafenib and trametinib in advanced <i>BRAF</i> V600–mutant melanoma: Efficacy and safety findings from parts 1 and 2 of the Phase III COMBI-i trial. (2020)

10028 Background: Treatment (tx) with checkpoint inhibitors or targeted therapy improves outcomes in patients (pts) with BRAF V600–mutant advanced melanoma; however, many pts subsequently progress and die. Preliminary evidence suggests that targeted therapy may enhance the impact of checkpoint inhibitors and improve efficacy compared with either treatment alone. Methods: COMBI-i is investigating first-line spartalizumab 400 mg every 4 wk + dabrafenib 150 mg twice daily + trametinib 2 mg once daily in pts with unresectable or metastatic BRAF V600–mutant melanoma (NCT02967692). We report efficacy and safety data from parts 1 (run-in cohort) and 2 (biomarker cohort), with a median follow-up of 24.3 mo. Response was assessed per RECIST v1.1. The randomized part 3 is ongoing. Results: 36 pts were enrolled (part 1: n = 9; part 2: n = 27); 20 (56%) had stage IV M1c disease and 15 (42%) had elevated lactate dehydrogenase (LDH) levels (≥ upper limit of normal). At the data cutoff (August 19, 2019), tx was ongoing in 10 pts (28%). The confirmed investigator-assessed objective response rate (ORR) was 78% (n = 28), with 16 complete responses (CRs; 44%) and 12 partial responses (33%). Median duration of response (DOR; 10/28 responders with events) was not reached (NR); 24-mo DOR rate was 53.4% (95% CI, 29%-73%). Median progression-free survival (PFS) was 22.7 mo; 24-mo PFS rate was 41.4% (95% CI, 23%-59%). At the cutoff, median overall survival (OS) was NR, with a 24-mo OS rate of 74.1% (95% CI, 56%-86%). In pts with elevated LDH, ORR was 67%, with 4 CRs (27%); median PFS was 10.7 mo (95% CI, 4.6-19.1 mo), and median OS was NR. The estimated 24-mo PFS and OS rates in these pts were 26.7% and 52.5%, respectively. All pts had ≥ 1 tx-related adverse event (TRAEs); 26 (72%) had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs were pyrexia (17%), increased lipase (11%), neutropenia (11%), increased blood creatine phosphokinase (8%), and increased γ-glutamyltransferase (8%). AEs leading to discontinuation of all 3 study drugs occurred in 6 pts (17%). All-causality grade ≥ 3 AEs requiring immunosuppressive medication occurred in 19 pts (53%). One pt died of cardiac arrest that was not considered tx related. Conclusions: The combination of spartalizumab + dabrafenib + trametinib resulted in high ORR and CR rates, with a high frequency of durable responses, including in patients with poor prognostic factors. Clinical trial information: NCT02967692.
Age-Related Differences in Remote Pointing Performance (1997)

The present study investigated age-related differences in remote pointing performance. Three age groups (i.e., the Young adult. Middle-aged, and Elderly) performed cursor positioning tasks by using a remote pointing device. The time taken to reposition the cursor was collected. The result showed that age groups had differences in movement time. Further analysis on the submovement duration times showed that movement time for the Young-adult group was mostly travel time, while the Elderly subjects spent most of their movement time on fine adjustment. This study supports the proposition that different age groups exhibit different kinds of movement patterns.
Major Implantation‐Induced Defects in Conventional and Rapid Annealed, Silicon Implanted LEC‐Grown GaAs (1991)

A major deep donor besides EL2 is found in Si implanted . This level emerges to be an implantation‐induced defect and lies at an energy between and . The EL2 defect distributions in conventional and rapid thermal annealed samples were also investigated. From the experimental defect distribution data, stress is believed to create dislocations which promote EL2 formation in rapid annealed samples, a stoichiometric process is found to be the major mechanism for creating EL2. The dependence of EL2 on the annealing temperature and implantation fluence are also obtained.
&lt;title&gt;New tunable lasers for potential use in lidar systems&lt;/title&gt; (1996)

We discuss the optical and laser properties of two new tunable laser crystals, Ce:LiSAF and Cr:ZnSe. These crystals are unique in that they provide a practical alternative to optical parametric oscillators as a means of generating tunable radiation in the near ultraviolet and mid-infrared regions (their tuning ranges are at least 285 - 315 nm and 2.2 - 2.8 microns, respectively). While these crystals are relatively untested in field deployment, they are promising and likely to be useful in the near future.
The Effectiveness of Whitelisting: a User-Study. (2008)

We believe this paper is the first extensive user-study of whitelisting email addresses. While whitelists are common in social networking and instant messaging (e.g., buddylists), they have not caught on in email systems. Instead, most of us use spam filters that try to identify all the senders we do not want to accept email from. With whitelists we only need to identify the much smaller set of users who can legitimately send us email- generally most of these users are known to us. In our study we built and deployed a whitelisting email service- named DOEmail- along with a Thunderbird add-on to try and make whitelists easy to manage. During the past two years, over 120 users have used DOEmail. As expected, we find that almost no spam makes it to users ’ inboxes, and less than 1 % of legitimate email is misclassified. We measure how hard it is for users to manage their whitelists, and conclude that after initial setup, the burden is very low. Our system uses challenge-response to identify whether unknown senders are legitimate. We give a quantitative evaluation of how effective challenge-response is, and the level of burden it places on the sender. 1
Ultra-fast correlation techniques using efficient third-harmonic generation in organic films (2003)

Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text M. Cha, G. Ramos-Ortiz, B. Kippelen, S. Thayumanavan, X. -. Y. Wang, S. R. Marder, and J. Mendez, "Ultra-fast correlation techniques using efficient third-harmonic generation in organic films," in Frontiers in Optics, OSA Technical Digest (CD) (Optica Publishing Group, 2003), paper MAA2. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Repeated Testing With the Hypertonic Saline Assay in Mice for Screening of Analgesic Activity (2018)

The repetition of i.pl. HS produces consistent reproducible responses without tissue damage. This results in efficient, rapid detection of analgesic activity, reducing the number of animals required.
Acoustic and perceptual speech characteristics of native Mandarin speakers with Parkinson's disease (2017)

This study examines acoustic features of speech production in speakers of Mandarin with Parkinson's disease (PD) and relates them to intelligibility outcomes. Data from 11 participants with PD and 7 controls are compared on several acoustic measures. In speakers with PD, the strength of association between these measures and intelligibility is investigated. Speakers with PD exhibited significant differences in fundamental frequency, pitch variation, vowel space, and rate relative to controls. However, in contrast to the English studies, speech rate was consistently slow and most strongly correlated with intelligibility. Thus, acoustic cues that strongly influence intelligibility in PD may vary cross-linguistically.
The immunotherapy prize! (2018)

Lelia Delamarre



The idea of stimulating the immune system to recognize and destroy cancer is more than 100 years old, but the development of effective immunotherapies has been challenging. The breakthrough came from the work of James Allison and colleagues, who elucidated that regulatory mechanisms fine tune the immune responses to ensure maximal efficacy against infected or abnormal cells without harming healthy tissues. Allison’s group and others showed that CD28 and CTLA-A4 are key molecules with opposite roles in the regulation of CD8 T cells, the primary population of immune cells responsible for recognizing and killing cancer cells and infected cells: CD28 enhances T cell activation, whereas CTLA-4 acts …
Effects of Physical Plasma on Biotechnological Processes in Mycelia of the Cultivated Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) (2016)

Physical plasma as the fourth state of matter comprises highly reactive particles (e.g., reactive species) and different types of radiation. It can be generated under standardized conditions at atmospheric pressure and low temperatures. Plasma is able to generate high-yielding bacterial strains, but this technique has not previously been applied to improve biotechnological processes in medicinal mushrooms. Our study investigated the influences of plasma on the growth and productivity of mycelial cultures of Ganoderma lucidum. Mycelia of G. lucidum were treated as solid pieces or suspended in Hagem medium using 3 different plasma sources: surface dielectric barrier discharge (DBD) plasma source, volume DBD plasma source, and the kINPen09 plasma jet. Treated mycelia were analyzed for biomass production, extract yield, and secondary metabolites. The plasma jet increased total triterpene content. Both DBD plasma sources led to elevated ergosterol content. Increased Β-l-3-D-glucan content was found after exposure to the volume DBD- or kINPen09-treated medium. The changes observed seemed to be dependent on total energy input by the plasma sources and the kind of mycelial treatment (solid piece or suspension; direct treatment or application of plasma-treated medium). In conclusion, physical plasma might be a useful tool for optimizing biotechnological processes in medicinal mushrooms. Further investigations are necessary to clarify whether these changes are stable and heritable, and whether effects can be achieved with other fungal species.
Evaluation of the mosaic model for polymer single crystals (1979)

Abstract By analogy with observed alteration of electron diffraction intensities from other crystalline long‐chain materials (e.g., paraffins) the mosaic model for polymer single crystals is evaluated. When many strong diffracted beams are excited simultaneously, the two‐beam dynamical diffraction theory (which then must be a consequence of the mosaic model) is shown not to be an adequate explanation of the electron diffraction intensities from such crystals; the n ‐beam dynamical theory is much more adequate. Further, observed bend contours in these crystals indicate significant bend distortion. This is confirmed by observed modulation of diffraction intensities which are well explained by Cowley's model for diffraction from elastically bent crystals. Other experiments on these crystals reveal the bends to be irregular. Rocking curves reveal that bends also explain diffraction line broadening, as also proposed by White. The most accurate description of molecular organic microcrystals is therefore that of a deformed foil and not a mosaic.
Role of Serum Factors and Adherent Cells in Cloning of Human T Lymphocytes in Agar Culture (1979)

In the presence of serum, 2-mercaptoethanol-treated bovine serum albumin enhances T cell colony formation as does 2-mercaptoethanol. The factor only partially substitutes for FCS, but neither for the mitogen phytohemagglutinin nor for conditioned medium derived from cultures of adherent cells.
Reexamination of the Jahn-Teller instability in<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mi mathvariant="normal">C</mml:mi><mml:mn>6</mml:mn></mml:msub><mml:mmultiscripts><mml:mi mathvariant="normal">H</mml:mi><mml:mn>6</mml:mn><mml:none/><mml:none/><mml:mo>+</mml:mo></mml:mmultiscripts></mml:mrow></mml:math>and<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mi mathvariant="normal">C</mml:mi><mml:mn>6</mml:mn></mml:msub><mml:mmultiscripts><mml:mi mathvariant="normal">H</mml:mi><mml:mn>6</mml:mn><mml:none/><mml:none/><mml:mo>−</mml:mo></mml:mmultiscripts></mml:mrow></mml:math> (2005)

The benzene cation $({\mathrm{C}}_{6}\mathrm{H}_{6}{}^{+})$ has a doublet $({e}_{1g})$ ground state in hexagonal ring $({D}_{6h})$ geometry. Therefore a Jahn-Teller (JT) distortion will lower the energy. The present theoretical study yields a model H\"uckel-type Hamiltonian that includes an electron-phonon coupling of the ${e}_{1g}$ electronic ground state with the two ${e}_{2g}$ vibrational modes: in-plane ring-bending and C-C bond-stretching. We treat also a third ${e}_{2g}$ C-H bending mode which has less influence. We obtain the electron-phonon couplings from density functional theory which gives a JT energy lowering of $1024\phantom{\rule{0.3em}{0ex}}{\mathrm{cm}}^{\ensuremath{-}1}$ in agreement with previous quantum chemistry calculations. We find a nonadiabatic solution for vibrational spectra and predict frequencies shifts of both the benzene cation and anion.
Epitaxial Bi<sub>5</sub>Ti<sub>3</sub>FeO<sub>15</sub>–CoFe<sub>2</sub>O<sub>4</sub> Pillar–Matrix Multiferroic Nanostructures (2013)

Epitaxial self-assembled ferro(i)magnetic spinel (CoFe2O4 (CFO)) and ferroelectric bismuth layered perovskite (Bi5Ti3FeO15 (BTFO)) pillar-matrix nanostructures are demonstrated on (001) single-crystalline strontium titanate substrates. The CFO remains embedded in the BTFO matrix as vertical pillars (∼50 nm in diameter) up to a volume fraction of 50%. Piezoresponse force microscopy experiments evidence a weak out-of-plane and a strong in-plane ferroelectricity in the BTFO phase, despite previously reported paraelectricity along the c-axis in a pure BTFO film. Phenomenological Landau-Ginzburg-Devonshire-based thermodynamic computations show that the radial stress induced by the CFO nanopillars can influence these ferroelectric phases, thus signifying the importance of the nanopillars. The CFO pillars demonstrate robust ferromagnetic hysteresis loops with little degradation in the saturation magnetization (ca. 4 μB/f.u.). Thus BTFO-CFO nanocomposites show significant promise as a lead-free magnetoelectric materials system.
Are slot and sub-wavelength grating waveguides better than strip waveguides for sensing? (2018)

The unique ability of slot and sub-wavelength grating (SWG) waveguides to confine light outside of the waveguide core material has attracted significant interest in their application to chemical and biological sensing. However, high sensitivity to sidewall roughness induced scattering loss in these structures compared to strip waveguides casts doubt on their efficacy. In this article, we seek to settle the controversy by quantitatively comparing the sensing performance of various waveguide geometries through figures of merit that we derive for each mode of sensing. These methods take into account both modal confinement and roughness scattering loss, the latter of which is computed using a volume-current (Green's-function) method with a first Born approximation. For devices based on the standard 220 nm silicon-on-insulator (SOI) platform whose propagation loss is predominantly limited by random line-edge sidewall roughness scattering, our model predicts that properly engineered TM-polarized strip waveguides claim the best performance for refractometry and absorption spectroscopy, while optimized slot waveguides demonstrate >5x performance enhancement over the other waveguide geometries for waveguide-enhanced Raman spectroscopy.
Conditional-ready mouse embryonic stem cell derived macrophages enable the study of essential genes in macrophage function (2015)

The ability to differentiate genetically modified mouse embryonic stem (ES) cells into functional macrophages provides a potentially attractive resource to study host-pathogen interactions without the need for animal experimentation. This is particularly useful in instances where the gene of interest is essential and a knockout mouse is not available. Here we differentiated mouse ES cells into macrophages in vitro and showed, through a combination of flow cytometry, microscopic imaging, and RNA-Seq, that ES cell-derived macrophages responded to S. Typhimurium, in a comparable manner to mouse bone marrow derived macrophages. We constructed a homozygous mutant mouse ES cell line in the Traf2 gene that is known to play a role in tumour necrosis factor-α signalling but has not been studied for its role in infections or response to Toll-like receptor agonists. Interestingly, traf2-deficient macrophages produced reduced levels of inflammatory cytokines in response to lipopolysaccharide (LPS) or flagellin stimulation and exhibited increased susceptibility to S. Typhimurium infection.
RNA Interference Directed against the Transglutaminase Gene Triggers Dysbiosis of Gut Microbiota in Drosophila (2016)

We recently reported that transglutaminase (TG) suppresses immune deficiency pathway-controlled antimicrobial peptides (IMD-AMPs), thereby conferring immune tolerance to gut microbes, and that RNAi of the TG gene in flies decreases the lifespan compared with non-TG-RNAi flies. Here, analysis of the bacterial composition of the Drosophila gut by next-generation sequencing revealed that gut microbiota comprising one dominant genus of Acetobacter in non-TG-RNAi flies was shifted to that comprising two dominant genera of Acetobacter and Providencia in TG-RNAi flies. Four bacterial strains, including Acetobacter persici SK1 and Acetobacter indonesiensis SK2, Lactobacillus pentosus SK3, and Providencia rettgeri SK4, were isolated from the midgut of TG-RNAi flies. SK1 exhibited the highest resistance to the IMD-AMPs Cecropin A1 and Diptericin among the isolated bacteria. In contrast, SK4 exhibited considerably lower resistance against Cecropin A1, whereas SK4 exhibited high resistance to hypochlorous acid. The resistance of strains SK1-4 against IMD-AMPs in in vitro assays could not explain the shift of the microbiota in the gut of TG-RNAi flies. The lifespan was reduced in gnotobiotic flies that ingested both SK4 and SK1, concomitant with the production of reactive oxygen species and apoptosis in the midgut, whereas the survival rate was not altered in gnotobiotic flies that mono-ingested either SK4 or SK1. Interestingly, significant amounts of reactive oxygen species were detected in the midgut of gnotobiotic flies that ingested SK4 and SK2, concomitant with no significant apoptosis in the midgut. In gnotobiotic flies that co-ingested SK4 and SK1, an additional unknown factor(s) may be required to cause midgut apoptosis.
Development of High-Strain-Rate Superplastic Oxide Ceramics Based on Flow Mechanism (2012)

In order to attain high-strain-rate superplasticity (HSRS) in ceramics, flow behavior was examined with ZrO 2 reference sample. The results suggest that the enhancement of the accommodation processes of grain boundary sliding (GBS) is important in addition to the careful controlling the microstructural factors, such as stable fine grain structure, reducing residual pores and so on. The spinel particles dispersion can simultaneously provide the following positive factors to ZrO 2 : i) suppressed grain growth due to pinning effect of spinel particles, enhanced accommodation due to ii) accelerated relaxation of stress concentrations exerted by GBS through dislocation motion and iii) accelerated lattice diffusion caused by the dissolution of aluminum and magnesium into ZrO 2 from the spinel particles. The positive factors due to spinel dispersion make it possible to attain HSRS in ZrO 2 ceramics.
Oxygen‐Containing Compounds Identified in Groundwater from Fuel Release Sites Using GCxGC‐TOF‐MS (2019)

Abstract This research continues a 7‐year study of oxygen‐containing organic compounds present in groundwater at gasoline and diesel fuel release sites that are quantified as diesel‐range “total petroleum hydrocarbons” when measured by methods utilizing solvent extraction and gas chromatography. Two‐dimensional gas chromatography with time‐of‐flight mass spectrometry was used to tentatively identify 1162 compounds (TICs) in 113 groundwater samples from 22 sites. Samples were collected from wells either upgradient of the release, within the source zone, or downgradient of the source but still within the plume of dissolved organics associated with release. The names and formulas of all TICs found in samples from each well type are presented and the results from upgradient and downgradient locations are compared in detail. About 60% of the most frequently detected TICs in downgradient wells were also detected in upgradient wells. A majority of these were saturated straight chain alkyl acids, commonly called fatty acids, or fatty acid esters. Of TICs frequently detected in downgradient wells but not upgradient wells, over half were branched alkyl alcohols. Hierarchical cluster analysis results suggest about 80% of the chemical composition of downgradient samples is more similar to upgradient samples than to source area samples. This similarity is due to the presence of the same types of fatty acids and esters. Principal component analysis indicates a continuum of biodegradation between the source area and downgradient samples with the latter becoming more consistent with upgradient samples. Results suggest some TICs may not be petroleum degradation intermediates but compounds synthesized by microorganisms through secondary production and carbon cycling.
Oil-in-Water Emulsification Induced by Ellipsoidal Hematite Colloids:  Evidence for Hydrolysis-Mediated Self-Assembly (2007)

We report on the preparation of a novel type of particle-stabilized oil-in-water emulsions. The emulsification mechanism comprises partial hydrolysis of the oil phase promoted by the alkaline surface of ellipsoidal hematite colloids stabilized by tetramethylammonium hydroxide. This mechanism yields monodisperse oil droplets with embedded single ellipsoidal particles. The emulsions, which are stable for at least several months, can be polymerized by radical initiation, to yield latex-like particles with interesting optical and magnetic properties due to their anisotropic hematite cores. Moreover, we show that complex composite core-shell colloids can be prepared by PMMA growth and silica deposition on polymerized emulsion droplets. Finally, as an example of a possible application for our system, we have measured translational and rotational diffusion coefficients of hematite-stabilized oil droplets by depolarized dynamic light scattering. The latter technique can also be employed to monitor the spontaneous emulsification in time.
Supplementary Table 7 from Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in &lt;i&gt;EGFR&lt;/i&gt;-Mutant NSCLC (2023)

&lt;p&gt;Platform-match 18 cases&lt;/p&gt;