gebhart/patrepeval huggingface dataset:
Abstract 4233: Generation of a Bicycle NK-TICA™, a novel NK cell engaging molecule designed to induce targeted tumor cytotoxicity (2022)

Abstract The tumor specific activation of natural killer (NK) cells is an area of active investigation in immune oncology, but to date has relied on complex biologic modalities (e.g., antibodies, fusion proteins, or cell therapies). NK cells are highly responsive immune cells that can detect and eliminate tumor cells and bridge innate to adaptive immune responses. Bicycles® are small (ca.1.5kDa), chemically synthetic, structurally constrained peptides discovered via phage display and optimized using structure-driven design and medicinal chemistry approaches. We have applied the Bicycle platform technology to identify Bicycles® that bind specifically to the key activating receptor, NKp46. When chemically coupled to tumor antigen binding Bicycles, this results in highly potent, antigen-dependent receptor activation and NK cell activation. We term this new class of fully synthetic molecules NK-TICAs and we will describe herein their discovery and evaluation.We demonstrate potent, selective binding of our Bicycles to receptor-expressing cells and the capability of the bifunctional molecule to induce NK cell function in vitro. With Bicycle’s novel NK-TICA™ compound, we demonstrate the engagement of NK cells, the specific activation and function of NK cells, and enhanced tumor cytotoxicity in a tumor target- and dose-dependent manner.In conclusion, NK-TICAs drive NK cell-mediated tumor cell killing and cytokine production in vitro and as such have the potential to catalyze the development of durable anti-tumor immunity in tumor types not well served by current therapies. We hypothesize that utilization of Bicycle NK-TICA™ as a multifunctional immune cell engager will promote the modulation of NK cells, as well as the infiltration and anti-tumor activity of NK cells in solid tumors. The data presented here provide initial proof of concept for the application of our Bicycle technology to drive NK cell-mediated tumor immunity. Citation Format: Fay J. Dufort, Christopher J. Leitheiser, Gemma Mudd, Julia Kristensson, Alexandra Rezvaya, Katie Gaynor, Sandra Uhlenbroich, Liudvikas Urbonas, Heather Scott, Liuhong Chen, Helen Harrison, Michael Skynner, Kevin McDonnell, Philip E. Brandish, Nicholas Keen. Generation of a Bicycle NK-TICA™, a novel NK cell engaging molecule designed to induce targeted tumor cytotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4233.
Heterogeneous Cellular Networks (2013)

This detailed, up-to-date introduction to heterogeneous cellular networking introduces its characteristic features, the technology underpinning it and the issues surrounding its use. Comprehensive and in-depth coverage of core topics catalogue the most advanced, innovative technologies used in designing and deploying heterogeneous cellular networks, including system-level simulation and evaluation, self-organisation, range expansion, cooperative relaying, network MIMO, network coding and cognitive radio. Practical design considerations and engineering tradeoffs are also discussed in detail, including handover management, energy efficiency and interference management techniques. A range of real-world case studies, provided by industrial partners, illustrate the latest trends in heterogeneous cellular networks development. Written by leading figures from industry and academia, this is an invaluable resource for all researchers and practitioners working in the field of mobile communications.
Camphor‐Enabled Transfer and Mechanical Testing of Centimeter‐Scale Ultrathin Films (2018)

Camphor is used to transfer centimeter-scale ultrathin films onto custom-designed substrates for mechanical (tensile) testing. Compared to traditional transfer methods using dissolving/peeling to remove the support-layers, camphor is sublimed away in air at low temperature, thereby avoiding additional stress on the as-transferred films. Large-area ultrathin films can be transferred onto hollow substrates without damage by this method. Tensile measurements are made on centimeter-scale 300 nm-thick graphene oxide film specimens, much thinner than the ≈2 μm minimum thickness of macroscale graphene-oxide films previously reported. Tensile tests were also done on two different types of large-area samples of adlayer free CVD-grown single-layer graphene supported by a ≈100 nm thick polycarbonate film; graphene stiffens this sample significantly, thus the intrinsic mechanical response of the graphene can be extracted. This is the first tensile measurement of centimeter-scale monolayer graphene films. The Young's modulus of polycrystalline graphene ranges from 637 to 793 GPa, while for near single-crystal graphene, it ranges from 728 to 908 GPa (folds parallel to the tensile loading direction) and from 683 to 775 GPa (folds orthogonal to the tensile loading direction), demonstrating the mechanical performance of large-area graphene in a size scale relevant to many applications.
1306Fast simulation of standard 12-lead ECG and 3d ventricular activation (2017)

classic HRV approach and for this reason should be used with caution.
Synthesis and structure-activity relationships for tetrahydroisoquinoline-based inhibitors of Mycobacterium tuberculosis (2020)

A series of 5,8-disubstituted tetrahydroisoquinolines were shown to be effective inhibitors of M. tb in culture and modest inhibitors of M. tb ATP synthase. There was a broad general trend of improved potency with higher lipophilicity. Large substituents (e.g., Bn) at the tetrahydroquinoline 5-position were well-tolerated, while N-methylpiperazine was the preferred 8-substituent. Structure-activity relationships for 7-linked side chains showed that the nature of the 7-linking group was important; -CO- and -COCH<sub>2</sub>- linkers were less effective than -CH<sub>2</sub>- or -CONH- ones. This suggests that the positioning of a terminal aromatic ring is important for target binding. Selected compounds showed much faster rates of microsomal clearance than did the clinical ATP synthase inhibitor bedaquiline, and modest inhibition of mycobacterial ATP synthase.
Highly transparent, bright green, sol–gel-derived monolithic silica-(Tb,Ce)PO4 glass-ceramic phosphors (2014)

A cosolvent-free sol–gel method yields monolithic silica glasses containing (Tb,Ce)PO<sub>4</sub> nanocrystals, free from Rayleigh scattering, and exhibiting ultraviolet-induced bright green photoluminescence.
Enhanced light extraction in wafer-bonded p-side-up thin-film AlGaInP light emitting diodes via zinc oxide nanorods (2016)

ZnO nanorods grown via hydrothermal method on the aluminum-doped zinc oxide (AZO) thin film were used to fabricate high-brightness p-side-up thin-film AlGaInP light-emitting diodes (LEDs). The AZO thin film was not only used as current spreading layers but also as a seed layer of ZnO nanorods. The AZO thin film was prepared using atomic layer deposition. The ZnO nanorods improved light extraction, thus increasing the light output power of the LEDs. The output powers of LEDs with optimum ZnO nanorod structures were increased by 32% at an injection current of 700 mA, as compared with that of an LED with AZO thin film. The emission wavelength shifts of LEDs with an AZO thin film and optimum ZnO nanorod structure were 18 and 11 nm, respectively, when the injection current was increased from 20 to 1000 mA. The ZnO nanorods not only provide more light extraction but also keep the thermal stability of the LED device without any degradation. The results are promising for the developed high brightness AlGaInP LED applications with low fabrication cost through ZnO nanorods grown by hydrothermal method to enhance the light extraction efficiency.
72 The Choice of Hypoallergens for Fish and Peach to Develop Food Allergy Specific Immunotherapy (TheFAST Project) (2012)

BACKGROUND: Classical allergen-specific immunotherapy (SIT), using subcutaneous injections with food extracts, may be effective but dangerous due to anaphylactic side-effects. The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting persistent and severe allergy to fish (cod) and fruit (peach). Both are caused by a single major allergen, parvalbumin (Cyp c 1) and lipid transfer protein (Pru p 3), respectively. FAST will apply hypo-allergenic recombinant major allergens for SIT. METHODS: Two approaches were evaluated for achieving hypo-allergenicity, i.e. site-directed mutagenesis and chemical modification. Wildtype (wt) natural and recombinant allergens and the hypo-allergens were extensively purified and characterized physico-chemically. Their stability was tested and allergenicity was compared by CAP-inhibition and histamine release experiments while immunogenicity was tested in T-cell proliferation experiments and rabbit and mice immunizations. RESULTS: For Cyp c 1, the mutant without calcium-binding site showed up to a 1000 times reduced allergenicity, while secondary fold and immunogenicity (tested in human PBMC stimulations and by immunization of laboratory animals) were retained. Chemically modified Cyp c 1 demonstrated a reduced capacity to stimulate T-cells and showed less immunogenicity in rabbits. The calcium-binding mutant has been produced under GMP conditions. For Pru p 3, 5 potential hypoallergens were compared. The allergenicity was reduced to a similar extent (∼1000-fold) for both variants in which disulfide bridges were disrupted, i.e. either by mutagenesis or by reduction/alkylation. The modification resulted in loss of alpha-helical secondary structure. However, unexpectedly, the immunogenicity was also significantly lowered/absent. CONCLUSIONS: For the Cyp c 1 calcium-binding mutant we are preparing to enter Phase I clinical trials. For Pru p 3, we need to evaluate new molecules to generate a hypoallergenic mutant that retains immunogenicity.
Synthesis of Phosphorothioate Oligonucleotides with Stereodefined Phosphorothioate Linkages (2003)

A method for solid-phase synthesis of stereodefined PS-oligos via an oxathiaphospholane approach using pure P-diastereomers of nucleoside oxathiaphospholane monomers is described. The oxathiaphospholane monomers are synthesized by phosphitylation of 5'-O-DMTr-N-protected deoxyribonucleosides with 2-chloro-spiro-4,4-pentamethylene-1,3,2-oxathiaphospholane followed by sulfurization. The procedure is general and may be applied to other analogs, depending on the aldehyde (or mercaptoalcohol) used. Starting from an 18O-labeled mercaptoalcohol, the corresponding 18O-labeled phosphitylating reagent and nucleoside monomers can be obtained and used for synthesis of labeled stereodefined PS-oligos, which are useful for studying mechanisms of enzymatic reactions. Details are provided for chromatographic separation of the 5'-O-DMTr-N-protected-deoxyribonucleoside-3'-O-(2-thio-spiro-4,4-pentamethylene-1,3,2-oxathiaphospholane)s into their P-diastereomers, and for manual solid-phase synthesis of PS-oligos. Oxidation of 5'-O-DMTr-N-protected-deoxyribonucleoside-3'-O-(2-thio-spiro-4,4-pentamethylene-1,3,2-oxathiaphospholane)s with selenium dioxide yields their 2-oxo-analogs, which are suitable either for elongation of stereodefined PS-oligos with segments consisting of unmodified nucleotide units possessing phosphate internucleotide linkages, or for generating isotopomeric 18O-labeled PO-oligos of predetermined P-chirality.
GUIDELINES FOR PLACEMENT OF LONGITUDINAL BARRIERS ON SLOPES. VOLUME I: EXECUTIVE SUMMARY. FINAL REPORT (1984)

This research was undertaken to investigate longitudinal barrier impact performance when placed on nonlevel terrain. Tasks performed in this study included: a determination of typical conditions for which longitudinal barriers are placed on nonlevel terrain; an evaluation of the impact behavior of widely used barrier systems when placed on nonlevel terrain; and the development of guidelines for selection and placement of barriers on nonlevel terrain. This volume is an executive summary of the three-volume research report.
Multichannel Signal Enhancement Algorithms for Assisted Listening Devices: Exploiting spatial diversity using multiple microphones (2015)

In everyday environments, we are frequently immersed by unwanted acoustic noise and interference while we want to listen to acoustic signals, most often speech. Technology for assisted listening is then desired to increase the efficiency of speech communication, reduce listener fatigue, or just allow for enjoying undisturbed sounds (e.g., music). For people with normal hearing, assisted listening devices (ALDs) mainly aim to achieve hearing protection or increase listening comfort; however, for hearing-impaired individuals, as the most prominent user group so far, further progress of assisted listening technology is crucial for better inclusion into our world of pervasive acoustic communication.
IRF6 in development and disease: A mediator of quiescence and differentiation (2008)

Post utero development of the mammary gland is a complex developmental process characterized by states of rapid cell proliferation (branching morphogenesis) followed by functional differentiation (lactation) and the consequent apoptosis (involution) of the secretory mammary epithelial cell. This process is cyclical, such that involution returns the mammary gland to a near-virgin-like state capable of responding to morphogenic cues with each consecutive pregnancy. Importantly, many of the regulatory processes which oversee mammary gland development are corrupted or otherwise compromised during the development of breast cancer. For example, Interferon Regulatory Factor 6 (IRF6) is a novel protein with growth inhibitory properties that was initially identified in mammary epithelial cells through its interaction with maspin, a known tumor suppressor in normal breast tissue. Recent findings from our laboratory suggest that IRF6 functions synergistically with maspin to regulate mammary epithelial cell differentiation by acting on the cell cycle. This perspective focuses on the possible involvement of IRF6 in promoting differentiation by regulating exit from the cell cycle and entry into the G(0) phase of cellular quiescence, and how these new findings shed light on normal mammary gland development and the initiation and progression of breast cancer.
Laser Telemetric System (2020)

This chapter presents a design study of scanning laser-based measurement system suitable for industrial in-process measurement. The internal components of an Laser Telemetric System (LTS) are normally grouped into distinct subsystems: the transmitter, the receiver, and the controller, as shown in the diagram. The ultimate performance of the system is, of course, based on the composite effect of both types of error sources. Systematic noise may also cause dimensions that are exact multiples of the noise period to appear more stable than dimensions. The windows are necessary to protect the internal components of the LTS from environmental contaminants and air turbulence. The windows on an LTS are subjected to the same constraints as the other optical components of the system. The ideal motor for this system may be a brushless DC motor with a very accurate, high-resolution encoder and phase-locked speed control system.
Rylene and Related Diimides for Organic Electronics (2010)

Organic electron-transporting materials are essential for the fabrication of organic p-n junctions, photovoltaic cells, n-channel field-effect transistors, and complementary logic circuits. Rylene diimides are a robust, versatile class of polycyclic aromatic electron-transport materials with excellent thermal and oxidative stability, high electron affinities, and, in many cases, high electron mobilities; they are, therefore, promising candidates for a variety of organic electronics applications. In this review, recent developments in the area of high-electron-mobility diimides based on rylenes and related aromatic cores, particularly perylene- and naphthalene-diimide-based small molecules and polymers, for application in high-performance organic field-effect transistors and photovoltaic cells are summarized and analyzed.
ChemInform Abstract: New P‐Chiral Phosphates, Phosphorothioates, and Phosphoroselenothiates. (1987)

Abstract The P‐N bonds in the phosphoramidates (I), (IV), (VII), and (IX) are cleaved using sodium hydride in carbon disulfide.
Reach-Dependent Capacity in Optical Networks Enabled by OFDM (2009)

In today’s optical networks, the channel capacity is designed for the system’s maximum reach. By using OFDM, reach dependent capacity can be realized which improves the network performance substantially.
Managed-Pressure Drilling: What It Is and What It Is Not (2009)

Abstract Within the context of broad industry recognition of two drilling technologies, Underbalanced Drilling predates Managed Pressure Drilling (MPD) by at least a decade. While there are some similarities in some of the equipment and possibly in some of the techniques, the applications are different in their intent. This paper will discuss methodologies comparing Conventional, Underbalanced, and Managed Pressure Drilling Operations with respect to objectives, planning, drilling equipment and operations, and well control. The application of Managed Pressure Drilling was specifically created to give it an identity apart from Conventional Drilling and apart from Underbalanced Drilling. There appears to be some confusion with respect to methodology for Managed Pressure Drilling. What constitutes a Managed Pressure Drilling Operation? What constitutes an Underbalanced Drilling Operation? Are they actually the same? Does it matter? Figure 1 illustrates the general domains of Conventional Drilling Operations, Managed Pressure Drilling Operations, and Underbalanced Drilling Operations.
Modeling the Cathodic Region in Crevice Corrosion under a Thin Electrolyte Film Including Particulates (2006)

Crevice corrosion may be limited by the capacity of the external cathodic region to support anodic dissolution currents within the crevice. The analysis here focuses on behavior of metal surfaces covered by a thin (~microns) layer of the electrolyte film including particulates. The particulates can affect the cathode current capacity (Itotal) by increasing the solution resistance (volume effect) and by decreasing the electrode area (surface effect). This work simulates and characterizes the effect of a uniform particulate monolayer on the cathode current capacity for steady state conditions in the presence of a thin electrolyte film. Particulate configurations with varying particle size, shape, arrangement, volume fraction, and electrode area coverage were numerically modeled as a function of the properties of the system. It is observed that the effects of particles can be fully accounted for in terms of two corrections: the volume blockage effect on the electrolyte resistivity can be correlated using Bruggeman's equation, and the electrode coverage effect can be modeled in terms of a simple area correction to the kinetics expression. For the range of parameters analyzed, applying these two correction factors, cathodes covered with thin electrolyte films that contain particles can be represented in terms of equivalent homogenous electrolytes that can then be analyzed using simpler approaches. Continuing work will examine the effects of greater volume fractions of particles and multiple particle layers.
Earthquake Response of Five Story Reinforced Concrete Masonry Test Building (1986)

In 1986, a full-scale five story reinforced masonry test building is to be constructed in the Japan Building Research Institute Large-Scale Structure Test Laboratory, and through 1987 to 1988, tests will be carried out in order to evaluate its seismic performance. At present, preliminary design and analyses of the test building are being carried out. In this paper, results of ineleastic dynamic response analyses of the test building are introduced.
An Input-Powered Vibrational Energy Harvesting Interface Circuit With Zero Standby Power (2011)

This paper presents an input-powered energy-harvesting interface circuit that eliminates standby power consumption by automatically shutting down when the ac input voltage amplitude is too low for successful energy reclamation. This feature eliminates the need for precharging the load and allows for indefinitely long intervals between energy harvesting cycles. The interface comprises two subcircuits: an input-powered ac/dc converter and an input-powered dc/dc boost converter with regulated output. The two subcircuits are separately fabricated in the ON Semi 3M-2P 0.5 μm CMOS process. The entire interface circuit starts up when the ac input amplitude exceeds 1 V and supplies a regulated dc output up to 3 V. When the input amplitude drops below 600 mV, the interface automatically enters standby mode and consumes no power. The system achieves a maximum efficiency of 60% with 1.5-V ac input amplitude and 3 V regulated dc output, delivering 3.9 mW of output power. The interface also functions properly in tests with an electrodynamic (magnetic) vibrational energy harvester.
Supplementary Data from Global Targeting of Subcellular Heat Shock Protein-90 Networks for Therapy of Glioblastoma (2023)

Supplementary Data from Global Targeting of Subcellular Heat Shock Protein-90 Networks for Therapy of Glioblastoma
α-helix to β-hairpin transition of human amylin monomer (2013)

The human islet amylin polypeptide is produced along with insulin by pancreatic islets. Under some circumstances, amylin can aggregate to form amyloid fibrils, whose presence in pancreatic cells is a common pathological feature of Type II diabetes. A growing body of evidence indicates that small, early stage aggregates of amylin are cytotoxic. A better understanding of the early stages of the amylin aggregation process and, in particular, of the nucleation events leading to fibril growth could help identify therapeutic strategies. Recent studies have shown that, in dilute solution, human amylin can adopt an α-helical conformation, a β-hairpin conformation, or an unstructured coil conformation. While such states have comparable free energies, the β-hairpin state exhibits a large propensity towards aggregation. In this work, we present a detailed computational analysis of the folding pathways that arise between the various conformational states of human amylin in water. A free energy surface for amylin in explicit water is first constructed by resorting to advanced sampling techniques. Extensive transition path sampling simulations are then employed to identify the preferred folding mechanisms between distinct minima on that surface. Our results reveal that the α-helical conformer of amylin undergoes a transformation into the β-hairpin monomer through one of two mechanisms. In the first, misfolding begins through formation of specific contacts near the turn region, and proceeds via a zipping mechanism. In the second, misfolding occurs through an unstructured coil intermediate. The transition states for these processes are identified. Taken together, the findings presented in this work suggest that the inter-conversion of amylin between an α-helix and a β-hairpin is an activated process and could constitute the nucleation event for fibril growth.