gebhart/patrepeval huggingface dataset:
Abstract 1694: Systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment increases T cell receptor diversity in localized and metastatic prostate cancer patients (2017)

Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) is frequently utilized as an adjuvant in cancer immunotherapies, and has known effects as a growth factor. However the extent to which GM-CSF modulates the adaptive immune response, including possible effects on the antigenic repertoire, remains unclear. We used next-generation sequencing of T cell receptor (TCR) beta chain sequences amplified from total RNA from peripheral blood mononuclear cells using consensus primers to assess changes in the circulating antigenic repertoire of prostate cancer patients treated with GM-CSF in multiple clinical trials. Administration of systemic GM-CSF monotherapy to patients with localized prostate cancer prior to planned radical prostatectomy (NCT00305669) results in a significant decline in clonality from the pre-treatment timepoint to the 2-week timepoint on treatment, indicative of increased early repertoire diversity (p=0.039 by Wilcoxon signed rank test). In a separate clinical trial (NCT00064129), the combination of systemic GM-CSF (250 μg/m2/day on days 1-14 of each cycle) with ipilimumab in metastatic castrate-resistant prostate cancer (mCRPC) patients also resulted in a significant decline in clonality from pre-treatment samples to the 2-week timepoint on treatment (p=0.002). In contrast, mCRPC patients who received ipilimumab alone in a separate study (NCT00323882) did not experience a similar decline in clonality after 3 weeks on treatment (p=0.625). In addition, comparison of the dynamics of specific clonotypes between the paired timepoints in the two mCRPC studies demonstrates that while there is no significant difference in the ratios of post-treatment to pre-treatment clonality between studies, patients treated with the combination of iplilimumab and GM-CSF show more repertoire change, with lower Morisita’s distance for all clones found at either timepoint (p=0.023), smaller intraclass correlation coefficient (p=0.028), and a smaller proportion of clonotypes that remain unchanged (defined by +/- 2-fold change for clones found at both timepoints) (p=0.002). These results indicate increased repertoire turnover when GM-CSF is combined with checkpoint inhibition. Hence data from both localized and metastatic prostate cancer, and from monotherapy and combination therapy regimens, supports a role for GM-CSF in inducing early diversification of the TCR repertoire. Citation Format: David Y. Oh, Li Zhang, Jason Cham, Alan Paciorek, Mark Klinger, Malek Faham, Susan F. Slovin, Lawrence Fong. Systemic granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment increases T cell receptor diversity in localized and metastatic prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1694. doi:10.1158/1538-7445.AM2017-1694
Purified interleukin-1 (IL-1) from human monocytes stimulates acute-phase protein synthesis by rodent hepatocytes in vitro. (1987)

A universal component of inflammation is the increased synthesis of a series of plasma proteins (acute-phase proteins) by the liver. The postulated messenger of acute-phase protein induction is released by leucocytes at the site of inflammation and has been shown to co-purify with endogenous pyrogen or lymphocyte-activating factor. Interleukin-1, molecular weight 17,000, pI 6 X 8-7 X 2, was purified to homogeneity from adherent human blood monocytes by a combination of affinity chromatography, gel filtration and isoelectric focusing. We examined the direct effect of pure IL-1 on the induction of acute-phase protein synthesis in vitro using rat and mouse hepatocytes. IL-1 caused significant increased synthesis of alpha 1-acid glycoprotein and smaller increases in the synthesis of other acute-phase proteins, and significant decreased synthesis of albumin. The pattern of induction of acute-phase proteins differs from that seen with a separate 30,000 molecular weight hepatocyte-stimulating factor from human monocytes described previously. We conclude that human IL-1 is one of the mediators responsible for the acute-phase protein response of the liver in inflammation and can directly cause stimulation of specific gene expression in normal hepatocytes.
Path planning for UAVs (2000)

In this paper, a two step path-planning algorithm for UAVs is proposed. The algorithm generates a stealthy path through a set of enemy radar sites of known location, and provides an intuitive way to trade-off stealth versus path length. In the first step, a suboptimal rough-cut path is generated through the radar sites by constructing and searching a graph based on Voronoi polygons. In the second step, a set of nonlinear ordinary differential equations are simulated, using the graph solution as an initial condition. The ODEs describe the dynamics of a set of virtual masses located in a virtual force field. The virtual forces push the masses away from the radar and toward one another. The ODEs are simulated to find a locally, exponentially stable equilibrium solution, which is interpreted as the optimal path. A simulation is provided to illustrate the idea.
Evaluation of predictive biomarkers for nivolumab in patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC) from the CheckMate-025 (CM-025) trial. (2020)

5023 Background: We previously showed that levels of CD8+ tumor infiltrating cells (TIC) expressing PD-1 but not TIM-3 and LAG-3 (CD8 + PD1 + TIM3 − LAG3 − ) were associated with response to nivolumab (nivo) in pretreated mccRCC pts (Pignon et al, 2019). Here, we sought to validate these findings in a randomized Phase III trial of nivo versus everolimus (evero) (CM-025) and explore the association of the biomarker with transcriptomic profiles. Methods: Tumor tissues from the CM-025 trial were analyzed (nivo arm: n = 116, evero arm: n = 107). Density/percentage of CD8 + PD1 + TIM3 − LAG3 − TIC was evaluated by immunofluorescence (IF) and PD-L1 expression on tumor cells (TC) was evaluated by IHC. Linear association with outcomes was assessed using binary logistic (ORR, clinical benefit (CB) defined as CR/PR and PFS≥12 months) and Cox PH (PFS, OS) regression models (1-sided p-values shown). Bulk RNA-seq was performed in a subset of samples (n = 71) and data analyzed using ssGSEA and Gene Signature Scores (GSS). Results: In the nivo arm, density of CD8 + PD1 + TIM3 − LAG3 − TIC (IF biomarker) was associated with ORR (OR = 1.43, p = 0.03) and CB (OR = 1.54, p = 0.02) while a trend was observed with PFS (HR = 0.87, p = 0.06). At an optimized cutoff, nivo treated pts with high IF biomarker (24/116, 20.7%) had higher ORR (45.8% vs 19.6%, p = 0.01) and CB (33.3% vs 14.1%, p = 0.03) and longer median PFS (9.6 vs 3.7 months, p = 0.03) than pts with low IF biomarker. A significant interaction between the IF biomarker and treatment was seen for both PFS and OS (2-sided p = 0.02 and 2-sided p = 0.08, respectively; significance determined as p &lt; 0.15). By bulk RNA-seq, several inflammatory pathways (FDR q &lt; 0.1) and inflammatory GSS (FDR q &lt; 0.05) were enriched in the high IF biomarker group. When combined with the IF biomarker, TC PD-L1 expression (≥1%) further separated clinical outcomes (ORR, CB and PFS) in the nivo arm. In the evero arm, the IF biomarker was neither prognostic nor predictive of any clinical outcome. Conclusions: High levels of CD8 + PD1 + TIM3 − LAG3 − TIC predicted response to nivo (but not to control evero) in mccRCC pts and were associated with activation of inflammatory response. Combination with TC PD-L1 further improved its predictive value, confirming our previous findings (Pignon et al, 2019). Further validation in the setting of first-line anti-PD-1 therapy is ongoing.
Density of states of a binary Lennard-Jones glass (2003)

We calculate the density of states of a binary Lennard-Jones glass using a recently proposed Monte Carlo algorithm. Unlike traditional molecular simulation approaches, the algorithm samples distinct configurations according to self-consistent estimates of the density of states, thereby giving rise to uniform internal-energy histograms. The method is applied to simulate the equilibrium, low-temperature thermodynamic properties of a widely studied glass former consisting of a binary mixture of Lennard-Jones particles. We show how a density-of-states algorithm can be combined with particle identity swaps and configurational bias techniques to study that system. Results are presented for the energy and entropy below the mode coupling temperature.
A class of exact solutions of the Navier-Stokes equations in three and four dimensions (2022)

A few basic, intuitive, properties of the Navier-Stokes system of equations for incompressible fluid flows are discussed in this paper. We present a rephrased interpretation of the Navier-Stokes equation in a space having an arbitrary number of dimensions. We then derive spatially periodic solutions for the velocity and pressure fields that span an unbounded domain in three and four dimensions, given a smooth solenoidal initial velocity vector field. In these solutions all velocity components depend non-trivially on all coordinate directions.
Effects of thermal stress on amount, composition, and antibacterial properties of coral mucus (2019)

The surface mucus layer of reef-building corals supports feeding, sediment clearing, and protection from pathogenic invaders. As much as half of the fixed carbon supplied by the corals' photosynthetic symbionts is incorporated into expelled mucus. It is therefore reasonable to expect that coral bleaching (disruption of the coral-algal symbiosis) would affect mucus production. Since coral mucus serves as an important nutrient source for the entire reef community, this could have substantial ecosystem-wide consequences. In this study, we examined the effects of heat stress-induced coral bleaching on the composition and antibacterial properties of coral mucus. In a controlled laboratory thermal challenge, stressed corals produced mucus with higher protein (<i>β</i> = 2.1, <i>p</i> < 0.001) and lipid content (<i>β</i> = 15.7, <i>p</i> = 0.02) and increased antibacterial activity (likelihood ratio = 100, <i>p</i> < 0.001) relative to clonal controls. These results are likely explained by the expelled symbionts in the mucus of bleached individuals. Our study suggests that coral bleaching could immediately impact the nutrient flux in the coral reef ecosystem via its effect on coral mucus.
Damage mechanisms of random fibrous networks (2015)

Published under licence in Journal of Physics: Conference Series by IOP Publishing Ltd. Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.” It was published in the Journal of Physics: Conference Series (JPCS), Conference 628:012093, doi: 10.1088/1742-6596/628/1/012093.
ChemInform Abstract: Synthesis of 4,8‐Substitutednaphtho[2,1‐b]thiophene Threading Intercalators. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Developments in Centrifugal Compressor Surge Control: A Technology Assessment (1993)

There are a number of surge control schemes in current use for centrifugal compressors which are employed in natural gas transmission systems. Basically, these schemes consist of a set of detection devices which either anticipate surge or detect it at its inception, and a set of control devices which act to prevent surge from occurring. A patent search was conducted in an attempt to assess the level and direction of technology development over the last 20 years and to define the focus for future R&amp;D activities. In addition, the paper presents the current state of technology in three areas: surge control, surge detection and surge suppression. Patent data obtained from on-line databases showed that most of the emphasis has been on surge control rather than on detection and control and that the current trend in surge control will likely continue towards incremental improvement of a basic or conventional surge control strategy. Various surge suppression techniques can be grouped in two categories: i) those which are focused on better compressor interior design, and ii) others which attempt to suppress surge by external and operational means.
REAPER: A Reflexive Architecture For Perceptive Agents (2001)

This article describes the winning entries in the 2000 Association for the Advancement of Artificial Intelligence Mobile Robot Competition. The robots, developed by Swarthmore College, all used a modular hybrid architecture designed to enable reflexive responses to perceptual input. Within this architecture, the robots integrated visual sensing, speech synthesis and recognition, the display of an animated face, navigation, and interrobot communication. In the Hors d'Oeuvres, Anyone? event, a team of robots entertained the crowd while they interactively served cookies; and in the Urban Search-and-Rescue event, a single robot autonomously explored a section of the test area, identified interesting features, built an annotated map, and exited the test area within the allotted time.
Bicyclic Analogues of d-myo-Inositol 1,4,5-Trisphosphate Related to Adenophostin A:  Synthesis and Biological Activity (2001)

The high affinity of adenophostin A for 1D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] receptors may be related to an alteration in the position of its 2'-phosphate group relative to the corresponding 1-phosphate group in Ins(1,4,5)P(3). To investigate this possibility, two bicyclic trisphosphates 9 and 10, designed to explore the effect of relocating the 1-phosphate group of Ins(1,4,5)P(3) using a novel fused-ring system, were synthesized from myo-inositol. Biological evaluation of 9 and 10 at the Ins(1,4,5)P(3) receptors of hepatocytes showed that both were recognized by hepatic Ins(1,4,5)P(3) receptors and both stimulated release of Ca(2+) from intracellular stores, but they had lower affinity than Ins(1,4,5)P(3). This finding may be explained by considering the three-dimensional structures of 9 and 10 in light of recent studies on the conformation of adenophostin A.
UV, Blue and Green Vertical Cavity Lasers. (1995)

Abstract : Many potential military and commercial applications exist for compact visible lasers, such as high density storage and readout, and high definition, high brightness displays. At present there are no reliable compact laser sources available operating at shorter wavelengths than red. Blue and green lasers using II-VI materials been demonstrated but only last a few minutes at best. New developments in material growth, fabrication and laser device design have made near UV, blue and green semiconductor lasers a realistic possibility. In particular, vertical cavity lasers (VCLs) have some inherent properties which allow for the formation of these visible lasers. Vertical cavity lasers can be used to form efFicient frequency doubling structures. Vertical cavity lasers have been made which operate CW at room temperature at wavelengths from 650 to 1050 nm., therefore it is possible to produce second harmonic light at wavelengths between 325 and 525 nm. Efficient internal second harmonic conversion is made possible in a vertical cavity laser structure for two major reasons. First the structures can be made with near 100% reflectors so that the photon density is extremely high inside the cavity, and second the mirrors inherently transmit at the second harmonic. (MM)
Pole-by-Pole d-q Model of a Linear Induction Machine (1979)

The concept of d-q coupled circuits representing stator and rotor magnetic poles is widely used in the analysis of symmetrical round-rotor induction machines. In this paper conventional round-rotor theory is extended to the analysis of linear induction machines. In particular, a tenth order set of differential equations are derived which describe a basic model for a four pole machine. Higher order systems of equations are discussed which better incorporate leading and trailing end effects. The parameters used in the model are readily derived from classical round-rotor theory. The resulting model is inherently capable of simulating both steady-state and transient behavior.
Design of potent linear .alpha.-melanotropin 4-10-analogs modified in positions 5 and 10 (1989)

alpha-Melanocyte stimulating hormone (alpha-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) that has diverse physiological functions in addition to its reversible darkening of amphibian skins by stimulating melanosome dispersion within melanophores. On the basis of theoretical and experimental results from our laboratory and others, we have designed a group of 1-13, 4-13, and especially 4-10 analogues related to the superpotent analogue [Nle4,D-Phe7]alpha-MSH in which the Glu5 has been replaced with Asp5, and the Gly10 has been replaced with Lys10 and other basic amino acid residues in the 4-10 analogues, and in which Gly10 and Lys11 were interchanged in the longer peptide analogues. In the 1-13 and 4-13 series the Lys10, Gly11 analogues generally retained superpotency for the D-Phe7-containing analogues. Most interestingly, synthesis of Ac-[Nle4,Xxx5,Yyy7,Zzz10]alpha-MSH4-10-NH2 analogues where Xxx = Asp or Glu, Yyy = Phe or D-Phe, and Zzz = basic amino acids (Lys, Orn, alpha,gamma-diaminobutyric acid (Dab), and alpha,beta-diaminopropionic acid (Dpr] provided melanotropins with potencies up to 10 times that of the native hormone in stimulating frog (Rana pipiens) skin darkening and 8-50 times more potent than alpha-MSH in stimulating lizard (Anolis carolinensis) skin melanophores in vitro. To our knowledge, Ac-[Nle4,Asp5,D-Phe7,Dab10]alpha-MSH4-10-NH2, the most potent analogue, is the most potent melanotropin obtained thus far for the Anolis assay system. These results provide new insights into the structural and conformational requirements for biological potency of alpha-MSH and the differential structural and conformational requirements of alpha-MSH and its analogues at two different types of pigment cell receptors.
Packaging silicon photonics with polymer waveguides for 3D electro-optical integration (2017)

We have demonstrated packaging of a silicon photonic chip with polymer multimode waveguides on a package substrate in a face-up electro-optic 3D integration scheme. The optical loss at the die-to-package interface in O-band was measured to be 7.6dB, which agrees well with simulation.
Energy-efficiency in Decentralized Wireless Networks: A Game-theoretic\n Approach inspired by Evolutionary Biology (2014)

Energy efficiency is gaining importance in wireless communication networks\nwhich have nodes with limited energy supply and signal processing capabilities.\nWe present a numerical study of cooperative communication scenarios based on\nsimple local rules. This is in contrast to most of the approaches in the\nliterature which enforce cooperation by using complex algorithms and require\nstrategic complexity of the network nodes. The approach is motivated by recent\nresults in evolutionary biology which suggest that, if certain mechanism is at\nwork, cooperation can be favoured by natural selection, i. e. even selfish\nactions of the individual nodes can lead to emergence of cooperative behaviour\nin the network. The results of the simulations in the context of wireless\ncommunication networks verify these observations and indicate that\nuncomplicated local rules, followed by simple fitness evaluation, can generate\nnetwork behaviour which yields global energy efficiency.\n
Automated Assessment of Bone Age Using Deep Learning and Gaussian Process Regression (2018)

Bone age is an essential measure of skeletal maturity in children with growth disorders. It is typically assessed by a trained physician using radiographs of the hand and a reference model. However, it has been described that the reference models leave room for interpretation leading to a large inter-observer and intra-observer variation. In this work, we explore a novel method for automated bone age assessment to assist physicians with their estimation. It consists of a powerful combination of deep learning and Gaussian process regression. Using this combination, sensitivity of the deep learning model to rotations and flips of the input images can be exploited to increase overall predictive performance compared to only using the deep learning network. We validate our approach retrospectively on a set of 12611 radiographs of patients between 0 and 19 years of age.
Accelerating pathway evolution by increasing the gene dosage of chromosomal segments (2018)

Experimental evolution is a critical tool in many disciplines, including metabolic engineering and synthetic biology. However, current methods rely on the chance occurrence of a key step that can dramatically accelerate evolution in natural systems, namely increased gene dosage. Our studies sought to induce the targeted amplification of chromosomal segments to facilitate rapid evolution. Since increased gene dosage confers novel phenotypes and genetic redundancy, we developed a method, Evolution by Amplification and Synthetic Biology (EASy), to create tandem arrays of chromosomal regions. In <i>Acinetobacter baylyi</i>, EASy was demonstrated on an important bioenergy problem, the catabolism of lignin-derived aromatic compounds. The initial focus on guaiacol (2-methoxyphenol), a common lignin degradation product, led to the discovery of <i>Amycolatopsis</i> genes (<i>gcoAB</i>) encoding a cytochrome P450 enzyme that converts guaiacol to catechol. However, chromosomal integration of <i>gcoAB</i> in <i>Pseudomonas putida</i> or <i>A. baylyi</i> did not enable guaiacol to be used as the sole carbon source despite catechol being a growth substrate. In ∼1,000 generations, EASy yielded alleles that in single chromosomal copy confer growth on guaiacol. Different variants emerged, including fusions between GcoA and CatA (catechol 1,2-dioxygenase). This study illustrates the power of harnessing chromosomal gene amplification to accelerate the evolution of desirable traits.
Flupentixol in der Therapie bei Suchterkrankungen (1996)

Neben den klassischen Indikationsbereichen für den Einsatz des Neuroleptikums Flupentixol bei schizophrenen Psychosen sind in den letzten Jahren eine Reihe weiterer möglicher Indikationsbereiche diskutiert und erforscht worden. Dazu gehören zum Beispiel Angsterkrankungen und affektive Störungen. Besonderes Interesse hat in den letzten Jahren aber auch der mögliche Einsatz von Flupentixol in der Therapie von Suchterkrankungen gefunden. Die Substanz ist bereits seit 1977 für die Behandlung von Suchterkrankungen registriert, wobei allerdings erst in den letzten Jahren systematische Therapiestudien initiiert wurden. Bevor der heutige Kenntnisstand zum Einsatz von Flupentixol bei Suchterkrankungen, wie Alkoholismus oder Kokainabhängigkeit, zusammenfassend dargestellt wird, soll ein theoretischer Überblick über die Bedeutung des dopaminergen Systems bei Suchterkrankungen gegeben werden.