gebhart/patrepeval huggingface dataset:
Targeted inhibition of IRAK-4 with emavusertib on immune remodeling in metastatic brain melanoma. (2023)

e21547 Background: The incidence of metastatic melanoma is on the rise, and 40-60% of patients will develop melanoma brain metastases (MBM). Frontline treatment consists of stereotactic radiosurgery given concurrently with immune checkpoint inhibition (ICI) or BRAF/MEK inhibition in BRAF mutated patients. While this therapy is effective at local control, the immune-suppressive nature of the CNS creates a permissive environment that facilitates distal intracranial relapse in over half of patients within 1 year. An improved understanding of the CNS tumor microenvironment (TME) is critical for designing effective treatments that improve MBM response to ICI. MyD88 is part of the inflammasome complex downstream of toll-like receptor or IL-1R receptor activation, and is aberrantly activated in the MBM TME. While critical for mediating innate immune activation, unrelenting stimulation of this pathway can trigger immune suppression through the reflexive recruitment of suppressive myeloid cells. Emavusertib (CA-4948) is a CNS permeable inhibitor of IRAK-4, a rate-limiting factor in the myddosome cascade. Thus, emavusertib may recondition the immunologic landscape of MBM through inhibition of myddosome induced myeloid infiltration, improving tumor response to ICI. Materials and Methods: Patient MBM tissues were examined by IHC to validate myddosome activation in the TME. Immunologic profiling of preclinical MBM tumors and PBMCs was performed via flow cytometry in response to anti-PD-1 ICI alone and in combination with emavusertib. Geospatial profiling of lymphocyte and myeloid cell distribution in single and combination treated MBM tumors was done using 3D imaging of cleared brain tissue. Overall survival was assessed in response to anti-PD-1 ICI treatment in combination with emavusertib. Results: In addition to promoting lymphocyte recruitment to MBM tumors, anti-PD-1 ICI significantly increases tumor infiltration by myeloid cells. Surface expression of PD-L1 was also elevated on myeloid cells in response to anti-PD-1 ICI. Microglia demonstrated no change in overall PD-L1 expression in response to either therapy, suggesting that peripheral myeloid cells are the principle target of therapy. Concomitant treatment with emavusertib alleviated ICI induced peripheral myeloid recruitment and reduced PD-L1 expression in MBM tumors while preserving effector lymphocyte infiltration. Emavusertib treatment also improved overall survival of mice when treated in combination with anti-PD-1 as compared to anti-PD-1 therapy alone. Conclusions: Emavusertib reconditions the MBM TME by mitigating the recruitment of infiltrating suppressive myeloid cells that likely confer resistance to anti-PD-1 ICI. This improves the anti-tumor efficacy of anti-PD-1 ICI, resulting in increased overall survival. Thus, emavusertib may be an effective adjuvant for improving treatment response to ICI in patients with MBM.
Limits to the power conversion efficiency of vertical-cavity surface-emitting lasers (1996)

Summary form only given. Reduction of electrical and optical losses in vertical-cavity surface-emitting lasers (VCSELs) through improved design, growth, and fabrication techniques has produced dramatic improvements in power conversion efficiency (PCE). In this paper simple analytical formulae based on realistic linear models are presented for maximum PCE as a function of electrical parameters, material gain coefficients, and optical losses, and optimum values are derived for design variables. The theoretical results are compared with published experimental data for high-efficiency vertical-cavity surface emitting lasers, and a comprehensive figure-of-merit, which relates directly to maximum theoretical PCE is discussed.
Porous ceramics for multistage Knudsen micropumps—modeling approach and experimental evaluation (2011)

This paper describes the evaluation of four types of porous ceramics for use as thermal transpiration materials in Knudsen pumps that operate at atmospheric pressure. Knudsen pumps are motionless gas pumps that utilize thermal transpiration along a channel or a set of channels; the channels must have a temperature gradient and must constrain the flow to remain within the free molecular or transitional flow regimes. Of the ceramics evaluated, a clay-based, 15 bar synthetic ceramic (15PC) presents the most favorable properties for Knudsen pumps. For an input power of 3.4 W, a 25 _ 25 mm 2 nine-stage Knudsen pump that uses this material provides a maximum pressure head of 12 kPa and a maximum gas flow rate of ≈3.7 µL min _1 . Reliability tests demonstrate more than 11 750 h of continuous operation without any deterioration in their gas pumping capabilities. A fitted model suggests that the temporal evolution of pressure at the sealed outlet of a Knudsen pump can be captured adequately using four parameters. These parameters correspond to various nonidealities that play dominant roles in the transient response of these pumps.
Harmonic Linearization Method for Computing the Motions of a Specific Type of Three-Joint Arms (2020)

Abstract The paper presents a three-joint arm that has two translational fifth-class kinematic pairs and a rotational one. The first two kinematic pairs are axially orthogonal, while the second and the third one are axially parallel. Such robots find use in machinery handling for arc welding. Systems of three nonlinear second-order differential equations were obtained to describe the motions of this arm. As it was necessary to assess the moment of load emerging on the control-drive shaft, the external generalized forces were reduced to a corresponding generalized coordinate. Harmonic linearization of nonlinearities was applied to analyze the arm system. This method can be used to fine the core properties of the system (frequency, amplitude, and phase of the oscillations; dependence of the form of nonlinearities or on the parameters of the linear part; etc.) without studying the transient.Ratios were obtained to find the parameters of natural oscillational motion occurring in such arms. These rations can be used to design and set up such an arm. The finding is that where the system of equations describing the motion of such an arm (including the drive motion equations) contains no prominent nonlinearities, these rations are a system of two algebraic frequency equations: a sixth-degree one and a fifth-degree one.
EUV resist development in Selete (2008)

The main development issue regarding EUV resist has been how to concurrently achieve high sensitivity, high resolution, and low line width roughness (LWR). This paper describes the current status of EUV resist development at Selete with a small field exposure tool (SFET). Selete standard resist 2 (SSR2) can simultaneously resolve 26-nm dense and isolated lines with the SFET. Our top data for resolution with annular illumination shows a 25-nm half-pitch. In evaluating resist performance, resist blur should be estimated separately from exposure tool fluctuations. By considering the aberration, flare, and actual illumination shape, resist blur can be estimated more accurately. We estimate the resist blur for SSR2 to be between 9.5 and 10.4 nm as sigma of the Gaussian convolution. We also present benchmarking results for suppliers' samples. Though sensitivity has been improved somewhat in some resists, further improvement is necessary. Further reduction of LWR is especially needed.
CCDC 1458994: Experimental Crystal Structure Determination (2016)

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
HIV-1 escapes from N332-directed antibody neutralization in an elite neutralizer by envelope glycoprotein elongation and introduction of unusual disulfide bonds (2016)

In the individual studied here, HIV-1 escaped from N332-glycan directed NAb responses without changing the epitope itself, but by elongating a variable loop that shields this epitope.
Data from Lentiviral-Driven Discovery of Cancer Drug Resistance Mutations (2023)

&lt;div&gt;Abstract&lt;p&gt;Identifying resistance mutations in a drug target provides crucial information. Lentiviral transduction creates multiple types of mutations due to the error-prone nature of the HIV-1 reverse transcriptase (RT). Here we optimized and leveraged this property to identify drug resistance mutations, developing a technique we term LentiMutate. This technique was validated by identifying clinically relevant EGFR resistance mutations, then applied to two additional clinical anticancer drugs: imatinib, a BCR-ABL inhibitor, and AMG 510, a KRAS G12C inhibitor. Novel deletions in BCR-ABL1 conferred resistance to imatinib. In KRAS-G12C or wild-type KRAS, point mutations in the AMG 510 binding pocket or oncogenic non-G12C mutations conferred resistance to AMG 510. LentiMutate should prove highly valuable for clinical and preclinical cancer-drug development.&lt;/p&gt;Significance:&lt;p&gt;LentiMutate can evaluate a drug's on-target activity and can nominate resistance mutations before they occur in patients, which could accelerate and refine drug development to increase the survival of patients with cancer.&lt;/p&gt;&lt;/div&gt;
Collaborative Enhancement of Endothelial Targeting of Nanocarriers by Modulating Platelet-Endothelial Cell Adhesion Molecule-1/CD31 Epitope Engagement (2015)

Nanocarriers (NCs) coated with antibodies (Abs) to extracellular epitopes of the transmembrane glycoprotein PECAM (platelet endothelial cell adhesion molecule-1/CD31) enable targeted drug delivery to vascular endothelial cells. Recent studies revealed that paired Abs directed to adjacent, yet distinct epitopes of PECAM stimulate each other's binding to endothelial cells in vitro and in vivo ("collaborative enhancement"). This phenomenon improves targeting of therapeutic fusion proteins, yet its potential role in targeting multivalent NCs has not been addressed. Herein, we studied the effects of Ab-mediated collaborative enhancement on multivalent NC spheres coated with PECAM Abs (Ab/NC, ∼180 nm diameter). We found that PECAM Abs do mutually enhance endothelial cell binding of Ab/NC coated by paired, but not "self" Ab. In vitro, collaborative enhancement of endothelial binding of Ab/NC by paired Abs is modulated by Ab/NC avidity, epitope selection, and flow. Cell fixation, but not blocking of endocytosis, obliterated collaborative enhancement of Ab/NC binding, indicating that the effect is mediated by molecular reorganization of PECAM molecules in the endothelial plasmalemma. The collaborative enhancement of Ab/NC binding was affirmed in vivo. Intravascular injection of paired Abs enhanced targeting of Ab/NC to pulmonary vasculature in mice by an order of magnitude. This stimulatory effect greatly exceeded enhancement of Ab targeting by paired Abs, indicating that '"collaborative enhancement"' effect is even more pronounced for relatively large multivalent carriers versus free Abs, likely due to more profound consequences of positive alteration of epitope accessibility. This phenomenon provides a potential paradigm for optimizing the endothelial-targeted nanocarrier delivery of therapeutic agents.
Operations of and Future Plans for the Pierre Auger Observatory (2009)

Contributions to the 31st ICRC, Lodz, Poland, July 2009
Self-Align-Gated GaN Field Emitter Arrays Sharpened by a Digital Etching Process (2021)

Field emitters are attracting much attention recently because of their potential for high-frequency and harsh-environment applications. Although silicon is the most studied semiconductor for field emitters, III-Nitrides are also very promising thanks to their tunable electron affinities. Two main challenges exist for low turn-on-voltage III-Nitrides field emitters: lack of a self-aligned gate and tip-sharpening technologies. In this work, we demonstrate self-aligned-gated GaN field emitter arrays whose tips are sharpened by a wet-based digital etching technology. This technology allows to reduce the tip size from 40 nm down to 20 nm. Gated GaN field emitters with a turn-on voltage (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">GE,ON</sub> ) of 20 V and current density of 150 mA/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">GE</sub> = 50 V have been demonstrated.
Multicentre, prospective, randomised study comparing the diagnostic yield of colon capsule endoscopy versus CT colonography in a screening population (the TOPAZ study) (2020)

ClinicalTrials.gov no: NCT02754661.
A Structure from Motion Approach using Constrained Deformable Models and Appearance Prediction (2002)

In this technical report, we address the problem of recovering 3-D models from sequences of uncalibrated images with unknown correspondence. To that end, we integrate tracking, structure from motion with geometric constraints, and use of deformable 3-D models in a single framework. The key to making the proposed approach work is the use of appearance-based model matching and refinement. This appearance-based constrained structure from motion (AbCSfm) approach is especially useful in recovering shapes of objects whose general structure is known but which may have little discernable texture in significant parts of their surfaces. We applied the proposed approach to 3D face modeling from multiple images to create new 3-D faces for DECface, a synthetic talking head developed at Cambridge Research Laboratory, Digital Equipment Corporation. The DECface model comprises a collection of 3-D triangular and rectangular facets, with nodes as vertices. In recovering the DECface model, we assume tha...
Supplementary Table S4 from Identification and Validation of Colorectal Neoplasia–Specific Methylation Markers for Accurate Classification of Disease (2023)

Supplementary Table S4 from Identification and Validation of Colorectal Neoplasia–Specific Methylation Markers for Accurate Classification of Disease
Effects of historical withdrawals on advective transport of contaminated ground waters in a glacial-drift aquifer, Milford, New Hampshire (1997)

The long-term persistence of some contaminants in the subsurface causes contaminant plumes in ground water to incorporate the effects of previous longterm trends in ground-water recharge and withdrawals. If changes in these aquifer stresses are significant during the period of contamination, the size of the contaminant plume will increase. Therefore, it is important to understand the relation between the current distribution of contaminants and previous aquifer stresses.
Reactivity of [{M(C6F5)2(μ-OH)}2]2- (M = Pd or Pt) toward Aromatic Amines and Malononitrile (1999)

Binuclear μ-hydroxo-μ-arylamido complexes [Pd2(C6F5)4(μ-OH)(μ-NHR)]2- (R = C6H5, C6H4Cl-p, C6H4F-p) and di-μ-arylamido complexes [M2(C6F5)4(μ-NHR)2]2- (M = Pd, R = C6H5, C6H4Cl-p, C6H4F-p, C6H4NO2-p, C6F5; M = Pt, R = C6H4NO2-p, C6F5) have been prepared by reaction of [M2(C6F5)4(μ-OH)2]2- with the corresponding arylamine RNH2 in 1:1 or 1:2 molar ratio, respectively. The reaction of [Pd2(C6F5)4(μ-NHPh)2]2- with CS2 leads to the formation of the mononuclear dithiocarbamate complex [Pd(C6F5)2(S2CNHPh)]-. Malononitrile and methyl cyanoacetate react with [Pd2(C6F5)4(μ-OH)2]2- in methanol to give the binuclear complexes [Pd2(C6F5)4{μ-CH(CN)CN}2]2- and [Pd2(C6F5)4{μ-CH(CO2Me)CN}2]2-. However the reaction of [Pd2(C6F5)4(μ-OH)2]2- with malononitrile in boiling methanol gives the mononuclear diiminato complex [Pd(C6F5)2{NHC(OMe)CHC(OMe)NH}]-. In wet toluene [Pd2(C6F5)4(μ-OH)2]2- produces the cyclotrimerization of malononitrile, giving 4,6-diamino-2-cyanomethyl-3,5-pyridinedicarbonitrile. The structures of [Pd2(C6F5)4(μ-NHC6F5)2]2- and [Pd2(C6F5)4{μ-CH(CN)CN}2]2- have been determined by X-ray diffraction.
Synthesis of a multiple-peak spatial degree of coherence for imaging through absorbing media (2005)

The synthesis of a multiple-peak spatial degree of coherence is demonstrated. This degree of coherence enables us to scan different sample points on different altitudes simultaneously and thus decreases the acquisition time. The multipeak degree of coherence is also used for imaging through an absorbing layer with different thicknesses or different indices of refraction along the layer. All our experiments are performed with a quasi-monochromatic light source. Therefore problems of dispersion and inhomogeneous absorption are avoided. Our experimental results are presented.
Continuously-tunable-bandwidth acoustic-wave resonator-based bandstop filters and their multi-mode modeling (2016)

This paper reports on high-quality-factor (Q) acoustic-wave resonator (AWR)-based bandstop filters (BSFs) with continuously-variable stopband bandwidth (BW). They are based on mixed-technology resonant branches that are shaped by one acoustic-wave-lumped-element resonator (AWLR) and two lumped-element (LE) impedance inverters that are in-parallel cascaded to an all-pass-type network. Despite the use of AWRs, transfer functions with fractional bandwidths (FBWs) that are wider than the electromechanical coupling coefficient (k t 2) of the AWRs can be created and controlled through the integration of variable LE capacitors that preserve the AWR's high-Q characteristics. A coupling-matrix-based design approach that facilitates the prediction of high- and low-frequency spurious modes — typically present in a realistic AWR filter response — already at the synthesis level is presented for the first time for AWR-based BSFs. An experimental BSF prototype constructed with commercially-available surface acoustic wave (SAW) resonators was built and tested at 418 MHz for proof-of-concept purposes. It exhibits tunable BW between 0.18–0.71 MHz (0.55–2.2k t 2), passband insertion loss (IL) between 0.55–2 dB and maximum stopband attenuation between 25–40 dB (i.e., Q>8,000).
Phosphorescent OLED Materials with Breakthrough Spectral Line Shape and Operational Stability for Automotive Applications (2020)

We highlight recent breakthroughs enabling higher performance PHOLEDs for high efficacy automotive lighting and long operational lifetime automotive display applications. Red and amber emitters are demonstrated with high color purity (FWHM as low as 36nm) yielding high efficacy as well as long lifetime (LT). DCI-P3 green emission with 300,000 LT95 at 1,000 nits is demonstrated enabling long LT automotive displays.
Polyamide 6/silica hybrid materials by a coupled polymerization reaction (2015)

Polyamide 6/SiO<sub>2</sub>hybrid materials with an adjustable SiO<sub>2</sub>amount were produced by the coupled polymerisation of three monomeric components namely 1,1′,1′′,1′′′-silanetetrayltetrakis-(azepan-2-one), 6-aminocaproic acid and ε-caprolactam within one process.
High-Gradient Nanomagnets on Cantilevers for Sensitive Detection of Nuclear Magnetic Resonance (2012)

Detection of magnetic resonance as a force between a magnetic tip and nuclear spins has previously been shown to enable sub-10 nm resolution 1H imaging. Maximizing the spin force in such a magnetic resonance force microscopy (MRFM) experiment demands a high field gradient. In order to study a wide range of samples, it is equally desirable to locate the magnetic tip on the force sensor. Here we report the development of attonewton-sensitivity cantilevers with high-gradient cobalt nanomagnet tips. The damage layer thickness and saturation magnetization of the magnetic material were characterized by X-ray photoelectron spectroscopy and superconducting quantum interference device magnetometry. The coercive field and saturation magnetization of an individual tip were quantified in situ using frequency-shift cantilever magnetometry. Measurements of cantilever dissipation versus magnetic field and tip–sample separation were conducted. MRFM signals from protons in a polystyrene film were studied versus rf irradiation frequency and tip–sample separation, and from this data the tip field and tip-field gradient were evaluated. Magnetic tip performance was assessed by numerically modeling the frequency dependence of the magnetic resonance signal. We observed a tip-field gradient ∂B(z)(tip)/∂z estimated to be between 4.4 and 5.4 MT m(–1), which is comparable to the gradient used in recent 4 nm resolution 1H imaging experiments and larger by nearly an order of magnitude than the gradient achieved in prior magnet-on-cantilever MRFM experiments.
Local inhibition of microtubule dynamics by dynein is required for neuronal cargo distribution (2017)

Abnormal axonal transport is associated with neuronal disease. We identified a role for DHC-1, the C. elegans dynein heavy chain, in maintaining neuronal cargo distribution. Surprisingly, this does not involve dynein's role as a retrograde motor in cargo transport, hinging instead on its ability to inhibit microtubule (MT) dynamics. Neuronal MTs are highly static, yet the mechanisms and functional significance of this property are not well understood. In disease-mimicking dhc-1 alleles, excessive MT growth and collapse occur at the dendrite tip, resulting in the formation of aberrant MT loops. These unstable MTs act as cargo traps, leading to ectopic accumulations of cargo and reduced availability of cargo at normal locations. Our data suggest that an anchored dynein pool interacts with plus-end-out MTs to stabilize MTs and allow efficient retrograde transport. These results identify functional significance for neuronal MT stability and suggest a mechanism for cellular dysfunction in dynein-linked disease.
Potential involvement of IL-8 in the pathogenesis of human cytomegalovirus infection (1998)

The observations that several types of viruses induced interleukin (IL)-8 production prompted us to investigate the interrelationship between IL-8 and cytomegalovirus (CMV) infection. CMV infection caused IL-8 production in a human monocytic cell line, THP-1, in dose- and time-dependent manners. Moreover, CMV induced IL-8 gene expression by concurrently activating transcription factors, NF-kappaB and AP-1. Furthermore, CMV infection of human fibroblast cell lines increased gene expression of a specific receptor for IL-8, CXCR1. IL-8 in turn enhanced CMV replication in a human embryonic fibroblast, MRC-5, in dose- and time-dependent manners. Augmented replication eventually culminated in the increased production of infectious CMV virions. Moreover, IL-8 can attenuate the antiviral activity of interferon (IFN), particularly that of alpha-type against picornaviruses such as encephalomyocarditis virus and poliovirus. The inhibitory effects were associated with reduced 2',5'-A oligoadenylate synthetase activity. These results would imply that CMV can induce IL-8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN.