gebhart/patrepeval huggingface dataset:
C-105 Clinical trial of HER2 cancer vaccine shows benefit in 45% of evaluable patients in phase I study (2019)

We have developed and tested therapeutic cancer vaccine targeting HER2-expressing cancers based on autologous dendritic cells (DCs) transduced with an adenovirus expressing the non-signaling extracellular and transmembrane domains of HER2, a driver oncogene in many cancers including breast, ovarian, lung, colorectal, gastroesophageal, and bladder, among others. In mice, the homologous vaccine cured virtually all mice with large established tumors up to 2 cm and with established macroscopic lung metastases. In mice, the protection was dependent on antibodies to HER2 that inhibited HER2 phosphorylation, but was FcR (ADCC) independent, and thus different from the main recognized mechanism of the clinically approved anti-HER2 monoclonal antibody, trastuzumab. A phase I trial is ongoing in patients with advanced metastatic cancers who have failed at least one line of standard therapy, whose tumors scored HER2 1+, 2+ or 3+ by immunohistochemistry or have a HER2 FISH score ≥1.8. Part 1 of the trial was carried out in patients naïve to trastuzumab or other HER2-directed therapies, as it is important to demonstrate safety in the absence of complicating effects of prior HER2-targeted therapies. In Part 1, although no responses were seen in 6 patients at the lowest dose of 5 million DCs, at the second and third dose escalations (10 and 20 million DCs), of 11 evaluable patients, 5 (45%) had clinical benefit, including one CR lasting 89 weeks, one PR lasting 24 weeks, and 3 cases of stable disease, seen in patients with metastatic ovarian, gastroesophageal or colorectal cancers. Adverse reactions were mainly injection site reactions that did not require treatment in most patients. Serial echocardiograms did not show any evidence of cardiotoxicity. The number of circulating tumor cells also decreased in 40% (8/20), 83% (5/6) and 100% (2/2) at 12, 28 and 48 weeks on study, respectively. Based on these results and safety data, the FDA and IRB have approved increasing the maximum dose to 40 million DCs and opening Part 2 of the trial in patients who have failed prior HER2-directed therapies like trastuzumab, mostly metastatic breast and gastric cancer patients. Early results in Part II starting at 20 million DCs already showed 2/6 patients with stable disease. Thus, we have translated a cancer vaccine from mice to human clinical trials with very promising early results, and intend to combine this vaccine with checkpoint inhibitors, as vaccines can induce T cell responses that turn “cold” tumors into “hot” ones amenable to checkpoint blockade immunotherapy.
Versatile synthesis of nanometer sized hollow silica spheresElectronic supplementary information (ESI) available: experimental; IR and XPS; AFM, SEM and TEM images. See http://www.rsc.org/suppdata/cc/b2/b212811j/ (2003)

Using the controlled precipitation of silicic acid on functionalized polystyrene latexes, nanometer sized silica-coated spheres could be prepared and subsequently modified to allow dispersion in non-aqueous solvents; removal of the interior polymer by calcination resulted in the formation of hollow silica spheres.
Influence of length on cytotoxicity of multi-walled carbon nanotubes against human acute monocytic leukemia cell line THP-1 in vitro and subcutaneous tissue of rats in vivo (2005)

Carbon nanotubes (CNTs) are single- or multi-cylindrical graphene structures that possess diameters of a few nanometers, while the length can be up to a few micrometers. These could have unusual toxicological properties, in that they share intermediate morphological characteristics of both fibers and nanoparticles. To date, no detailed study has been carried out to determine the effect of length on CNT cytotoxicity. In this paper, we investigated the activation of the human acute monocytic leukemia cell line THP-1 in vitro and the response in subcutaneous tissue in vivo to CNTs of different lengths. We used 220 nm and 825 nm-long CNT samples for testing, referred to as "220-CNTs" and "825-CNTs", respectively. 220-CNTs and 825-CNTs induced human monocytes in vitro, although the activity was significantly lower than that of microbial lipopeptide and lipopolysaccharide, and no activity appeared following variation in the length of CNTs. On the other hand, the degree of inflammatory response in subcutaneous tissue in rats around the 220-CNTs was slight in comparison with that around the 825-CNTs. These results indicated that the degree of inflammation around 825-CNTs was stronger than that around 220-CNTs since macrophages could envelop 220-CNTs more readily than 825-CNTs. However, no severe inflammatory response such as necrosis, degeneration or neutrophil infiltration in vivo was observed around both CNTs examined throughout the experimental period.
Reproducing Quantum Probability Distributions at the Speed of Classical Dynamics: A New Approach for Developing Force-Field Functors (2018)

Modeling nuclear quantum effects is required for accurate molecular dynamics (MD) simulations of molecules. The community has paid special attention to water and other biomolecules that show hydrogen bonding. Standard methods of modeling nuclear quantum effects like Ring Polymer Molecular Dynamics (RPMD) are computationally costlier than running classical trajectories. A force-field functor (FFF) is an alternative method that computes an effective force field that replicates quantum properties of the original force field. In this work, we propose an efficient method of computing FFF using the Wigner-Kirkwood expansion. As a test case, we calculate a range of thermodynamic properties of Neon, obtaining the same level of accuracy as RPMD, but with the shorter runtime of classical simulations. By modifying existing MD programs, the proposed method could be used in the future to increase the efficiency and accuracy of MD simulations involving water and proteins.
Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model (2001)

We studied the effects of bypass circuit surface heparinization on kallikrein-kinin, coagulation, fibrinolytic and complement activation in a closed model system for simulating veno-venous bypass (WBP) in orthotopic liver transplantation (OLT). The circuits were identical to those in routine use during clinical OLT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at a non-pulsatile flow (2 l/min) and at a constant temperature (37.5 degrees C) for 12 h. In 10 experiments, the entire inner surface of the circuits was coated with end-point attached heparin (HC). In the remaining 10, non-treated PVC tubing was used (NC). Components of the plasma kallikrein-kinin, coagulation, fibrinolytic and complement systems were analyzed using functional techniques (chromogenic peptide substrate assays) and enzyme immunoassays at baseline, 3 and 12 h. Significant activation of the initial (C3bc) and terminal (TCC) components of the complement system were found in both the NC and HC groups after 3 and 12 h: C3bc: NC: baseline = 4 (3.5-7.7), 3 h = 17.3* (12.5-27), 12h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8), 3h = 9* (6-14.4), 12h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3h = 5*(0.8-11.9), 12 h: 13.1* (4.2-25.7). HC: baseline = 0.5 (0.1-0.6), 3 h = 0.6* (0.1-0.8), 12 h = 1.2* (0.3-2) AU/ml; median and range (*: p < 0.05). The C3bc and TCC concentrations were significantly higher in the NC group at 3 and 12 h, compared to the HC group: C3bc (NC vs. HC group): 3 h, p < 0.001; 12 h, p < 0.001. TCC (NC vs. HC group): 3h, p < 0.001; 12 h, p < 0.001. Significant increases in the values of thrombin-antithrombin complexes (p = 0.003), prothrombin fragment 1 + 2 (p = 0.006) and plasmin-alpha2-antiplasmin complexes (p = 0.016) were found in the non-coated group, but not in the heparin-coated group during the observation period, showing that the coagulation and fibrinolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorporeal perfusion circuit used for WBP reduces activation of the plasma cascade systems in a closed venous system in vitro.
Xanthine-based acyclic nucleoside phosphonates with potent antiviral activity against varicella-zoster virus and human cytomegalovirus (2018)

While noncanonic xanthine nucleotides XMP/dXMP play an important role in balancing and maintaining intracellular purine nucleotide pool as well as in potential mutagenesis, surprisingly, acyclic nucleoside phosphonates bearing a xanthine nucleobase have not been studied so far for their antiviral properties. Herein, we report the synthesis of a series of xanthine-based acyclic nucleoside phosphonates and evaluation of their activity against a wide range of DNA and RNA viruses. Two acyclic nucleoside phosphonates within the series, namely 9-[2-(phosphonomethoxy)ethyl]xanthine (PMEX) and 9-[3-hydroxy-2-(phosphonomethoxy)propyl]xanthine (HPMPX), were shown to possess activity against several human herpesviruses. The most potent compound was PMEX, a xanthine analogue of adefovir (PMEA). PMEX exhibited a single digit µM activity against VZV (EC<sub>50</sub> = 2.6 µM, TK<sup>+</sup> Oka strain) and HCMV (EC<sub>50</sub> = 8.5 µM, Davis strain), while its hexadecyloxypropyl monoester derivative was active against HSV-1 and HSV-2 (EC<sub>50</sub> values between 1.8 and 4.0 µM). In contrast to acyclovir, PMEX remained active against the TK<sup>-</sup> VZV 07-1 strain with EC<sub>50</sub> = 4.58 µM. PMEX was suggested to act as an inhibitor of viral DNA polymerase and represents the first reported xanthine-based acyclic nucleoside phosphonate with potent antiviral properties.
Top-gated Ge-Si<inf>x</inf>Ge<inf>1&#x2212;x</inf> core-shell nanowire field-effect transistors with highly doped source and drain (2009)

Semiconductor (e.g. silicon, germanium) nanowires have gained interest as an attractive platform to fabricate field effect transistors devices because of their reduced short channel effects by comparison to planar devices. The realization of high performance nanowire devices however has been stymied primarily by large source (5) and drain (D) contact resistances. Here we report the fabrication and electrical characterization of the top-gated Ge-Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1-x</sub> core-shell nanowire field-effect transistors (NWFETs) with highly doped S/D. The highly doped S/D, realized using low energy ion implantation, allows an efficient carrier injection into the NWFET channel.
Fieldable Platform for Large-Scale Deposition of Concrete Structures (2024)

Oak Ridge National Laboratory’s Manufacturing Demonstration Facility is developing a novel, large-scale additive manufacturing, or 3D printing, system. The Sky Big Area Additive Manufacturing (SkyBAAM) system will ultimately be a fieldable concrete deposition machine with pick and place abilities that will allow for full-scale, automated construction of buildings. The system will be implemented with existing construction equipment meaning conventional cranes will be used to suspend the printhead. SkyBAAM will be cable-driven by four base stations and suspended from a single crane. The elimination of a gantry system, found commonly in large-scale additive manufacturing systems, will enable SkyBAAM to be quickly set up with minimal site preparation. The medium-scale version of SkyBAAM is currently in development. The system design, cable stiffness analysis, and tactics for freezing rotational degrees-of-freedom (DOF), detailed in this paper, will provide a basis for the final, large-scale version of the SkyBAAM system.
Transmembrane interactions and the mechanisms of transport of proteins across membranes (1978)

We have made observations, by double fluorescence staining of the same cell, of the distributions of surface receptors, and of intracellular actin and myosin, on cultured normal fibroblasts and other flat cells, and on lymphocytes and other rounded cells. The binding of multivalent ligands (a lectin or specific antibodies) to a cell surface receptor on flat cells clusters the cell receptors into small patches, which line up directly over the actin- and myosin-containing stress fibers inside the cell. Similar ligands binding to rounded cells can cause their surface receptors to be collected into caps on the surface, and these caps are invariably found to be associated with concentrations of actin and myosin under the capped membrane. Although these ligand-induced surface phenomena appear to be different on flat and rounded cells, we propose that in both cases clusters of receptors become linked across the membrane to actin- and myosin-containing structures. In flat cells these structures are very long stress fibers; therefore, when clusters of receptors become linked to these fibers, the clusters are immobilized. In round cells, membrane-associated actin- and myosin-containing structures are apparently much less extensive than in flat cells; therefore, clusters of receptors linked to these structures are still mobile in the plane of the membrane. We suggest that in this case the clusters are then actively collected into a cap by an analogue of the muscle sliding filament mechanism. To explain the transmembrane linkage, we propose that actin is associated with the plasma membrane as a peripheral protein which is directly or indirectly bound to an integral protein (or proteins) X of the membrane. Individual molecules of any receptor are not bound to X, but after they are specifically clustered into patches, a patch of receptors then becomes bound to S and hence to actin/myosin.
BioTherapeutics, Education and Research Foundation position paper: Assessing the competency of clinicians performing maggot therapy (2021)

In its mission to optimise the quality of patient care and the level of clinician training within the fields of biotherapy, the BioTherapeutics, Education and Research (BTER) Foundation and its Maggot Therapy Competency Committee identified qualities and achievements assessed to be the minimum standards that health care professionals should attain in order to be deemed competent in maggot therapy. The set of six standards were selected to reflect the same high degree of professionalism that is used by the Accreditation Council of Graduate Medical Education for assessing other medical specialists, but with an emphasis on the principles and practice of maggot therapy. For each domain in which competency is expected, the rationale has been explained, specific competencies have been articulated, and methods for demonstrating or evaluating those competencies have been suggested. Applicable to any clinician applying maggot dressings professionally, these recommendations should assist those who wish to identify, assess, or achieve competency in maggot therapy. Specifically, these six competencies include: (1) knowledge about wound care in general and maggot therapy in particular; (2) skill in general patient care, to a level commensurate with their professional role; (3) ability to communicate effectively with colleagues, patients, and the general public; (4) professional and ethical behaviour; (5) ability to deliver systems-based health care; (6) incorporation of continuing education and quality improvement into their practice.
High-power fiber amplifier using a PM Yb-doped photodarkening-resistant LMA fiber with depressed-clad index profile design (2010)

Based on a depressed-clad index profile design, a PM Yb-doped large mode area (LMA) fiber with an effective mode area of 450 &mu;m<sup>2</sup> was designed and fabricated. The fiber was used to amplify 10-ns pulses at 1064 nm with a repetition rate of 100 kHz, and an output energy higher than 200 &mu;J was obtained, within a bandwidth of 0.5 nm. The fiber was coiled on a 12-cm diameter mandrel to obtain a single-mode output having a measured M<sup>2</sup> value of 1.04. The output polarization extinction ratio was higher than 20 dB. The photodarkening excess loss of the Ytterbium//Phosphorus Aluminum co-doped fiber was measured to be a factor 5 lower than that of a reference Ytterbium/Aluminum co-doped fiber. It is shown how a depressed-clad index profile design can improve higher-order mode filtering while keeping the coiling diameter practical for compact fiber amplifier packaging.
Building a Microkinetic Model from First Principles for Higher Amine Synthesis on Pd Catalyst (2019)

The hydrogenation of nitriles utilizing heterogeneous catalysis is a significant commercial process for the synthesis of primary, secondary, and tertiary amines. Periodic plane-wave density functional theory (DFT) is used to examine the hydrogenation of acetonitrile to primary, secondary, and tertiary amines on palladium catalysts. The quantified minimum energy reaction pathways, including activation barriers, for acetonitrile reaction to higher amines are discussed. The construction of a microkinetic model from first-principles for higher amine synthesis is presented. In addition, the microkinetic model simulations are discussed and compared to palladium-based catalyst experimental results for higher amine synthesis. For the first time, this novel and robust reactor model provides detailed insights into surface species coverage, as a function of process conditions (e.g., feedstock ratio, catalyst type, temperature, and pressure). More broadly, process engineers can leverage this valuable information to guide reaction engineering efforts, including process optimization, reactor design, and catalyst selection.
Autoimmunity conferred by chs3-2D relies on CSA1, its adjacent TNL-encoding neighbour (2015)

Plant innate immunity depends on the function of a large number of intracellular immune receptor proteins, the majority of which are structurally similar to mammalian nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) proteins. CHILLING SENSITIVE 3 (CHS3) encodes an atypical Toll/Interleukin 1 Receptor (TIR)-type NLR protein with an additional Lin-11, Isl-1 and Mec-3 (LIM) domain at its C-terminus. The gain-of-function mutant allele chs3-2D exhibits severe dwarfism and constitutively activated defense responses, including enhanced resistance to virulent pathogens, high defence marker gene expression, and salicylic acid accumulation. To search for novel regulators involved in CHS3-mediated immune signaling, we conducted suppressor screens in the chs3-2D and chs3-2D pad4-1 genetic backgrounds. Alleles of sag101 and eds1-90 were isolated as complete suppressors of chs3-2D, and alleles of sgt1b were isolated as partial suppressors of chs3-2D pad4-1. These mutants suggest that SAG101, EDS1-90, and SGT1b are all positive regulators of CHS3-mediated defense signaling. Additionally, the TIR-type NLR-encoding CSA1 locus located genomically adjacent to CHS3 was found to be fully required for chs3-2D-mediated autoimmunity. CSA1 is located 3.9 kb upstream of CHS3 and is transcribed in the opposite direction. Altogether, these data illustrate the distinct genetic requirements for CHS3-mediated defense signaling.
Phenyl Dichlorophosphate (2001)

[770-12-7] C6H5Cl2O2P (MW 210.98) InChI = 1S/C6H5Cl2O2P/c7-11(8,9)10-6-4-2-1-3-5-6/h1-5H InChIKey = TXFOLHZMICYNRM-UHFFFAOYSA-N (DMSO activation for Pfitzner–Moffatt oxidation;1 activation of carboxylic acids for acylation of amine, alcohol, and azide nucleophiles;4-7 acetal and thioacetal cleavage;8 phosphorylating agent10) Alternate Names: PDCP; phenyl phosphorochloridate. Physical Data: bp 241–243 °C; d 1.412 g cm−3. Solubility: sol ethyl acetate (50 mg mL−1), most organic solvents. Form Supplied in: colorless liquid; commercially available. Purification: redistil under reduced pressure. Handling, Storage, and Precautions: corrosive; irritant; moisture sensitive; incompatible with strong bases.
Joint Training of Generic CNN-CRF Models with Stochastic Optimization (2015)

We propose a new CNN-CRF end-to-end learning framework, which is based on joint stochastic optimization with respect to both Convolutional Neural Network (CNN) and Conditional Random Field (CRF) parameters. While stochastic gradient descent is a standard technique for CNN training, it was not used for joint models so far. We show that our learning method is (i) general, i.e. it applies to arbitrary CNN and CRF architectures and potential functions; (ii) scalable, i.e. it has a low memory footprint and straightforwardly parallelizes on GPUs; (iii) easy in implementation. Additionally, the unified CNN-CRF optimization approach simplifies a potential hardware implementation. We empirically evaluate our method on the task of semantic labeling of body parts in depth images and show that it compares favorably to competing techniques.
Altered Signaling and Cell Cycle Regulation in Embryonal Stem Cells with a Disruption of the Gene for Phosphoinositide 3-Kinase Regulatory Subunit p85α (2003)

The p85alpha regulatory subunit of class I(A) phosphoinositide 3-kinases (PI3K) is derived from the Pik3r1 gene, which also yields alternatively spliced variants p50alpha and p55alpha. It has been proposed that excess monomeric p85 competes with functional PI3K p85-p110 heterodimers. We examined embryonic stem (ES) cells with heterozygous and homozygous disruptions in the Pik3r gene and found that wild type ES cells express virtually no monomeric p85alpha. Although, IGF-1-stimulated PI3K activity associated with insulin receptor substrates was unaltered in all cell lines, p85alpha-null ES cells showed diminished protein kinase B activation despite increased PI3K activity associated with the p85beta subunit. Furthermore, p85alpha-null cells demonstrated growth retardation, increased frequency of apoptosis, and altered cell cycle regulation with a G(0)/G(1) cell cycle arrest and up-regulation of p27(KIP), whereas signaling through CREB and MAPK was enhanced. These phenotypes were reversed by re-expression of p85alpha via adenoviral gene transfer. Surprisingly, all ES cell lines could be differentiated into adipocytes. In these differentiated ES cells, however, compensatory p85beta signaling was lost in p85alpha-null cells while increased signaling by CREB and MAPK was still observed. Thus, loss of p85alpha in ES cells induced alterations in IGF-1 signaling and regulation of apoptosis and cell cycle but no defects in differentiation. However, differentiated ES cells partially lost their ability for compensatory signaling at the level of PI3K, which may explain some of the defects observed in mice with homozygous deletion of the Pik3r1 gene.
Two-dimensional beam steering using a thermo-optic silicon photonic optical phased array (2016)

Many components for free-space optical (FSO) communication systems have shrunken in size over the last decade. However, the steering systems have remained large and power hungry. Nonmechanical beam steering offers a path to reducing the size of these systems. Optical phased arrays can allow integrated beam steering elements. One of the most important aspects of an optical phased array technology is its scalability to a large number of elements. Silicon photonics can potentially offer this scalability using CMOS foundry techniques. A phased array that can steer in two dimensions using the thermo-optic effect is demonstrated. No wavelength tuning of the input laser is needed and the design allows a simple control system with only two inputs. A benchtop FSO link with the phased array in both transmit and receive mode is demonstrated.