gebhart/patrepeval huggingface dataset:
Discovery and Optimization of a STING Agonist Platform for Application in Antibody Drug Conjugates (2023)

While STING agonists have proven to be effective preclinically as anti-tumor agents, these promising results have yet to be translated in the clinic. A STING agonist antibody-drug conjugate (ADC) could overcome current limitations by improving tumor accessibility, allowing for systemic administration as well as tumor-localized activation of STING for greater anti-tumor activity and better tolerability. In line with this effort, a STING agonist ADC platform was identified through systematic optimization of the payload, linker, and scaffold based on multiple factors including potency and specificity in both in vitro and in vivo evaluations. The platform employs a potent non-cyclic dinucleotide STING agonist, a cleavable ester-based linker, and a hydrophilic PEG8-bisglucamine scaffold. A tumor-targeted ADC built with the resulting STING agonist platform induced robust and durable anti-tumor activity and demonstrated high stability and favorable pharmacokinetics in nonclinical species.
Role of Pirh2 in Mediating the Regulation of p53 and c-Myc (2011)

Ubiquitylation is fundamental for the regulation of the stability and function of p53 and c-Myc. The E3 ligase Pirh2 has been reported to polyubiquitylate p53 and to mediate its proteasomal degradation. Here, using Pirh2 deficient mice, we report that Pirh2 is important for the in vivo regulation of p53 stability in response to DNA damage. We also demonstrate that c-Myc is a novel interacting protein for Pirh2 and that Pirh2 mediates its polyubiquitylation and proteolysis. Pirh2 mutant mice display elevated levels of c-Myc and are predisposed for plasma cell hyperplasia and tumorigenesis. Consistent with the role p53 plays in suppressing c-Myc-induced oncogenesis, its deficiency exacerbates tumorigenesis of Pirh2(-/-) mice. We also report that low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival. Collectively, our data reveal the in vivo roles of Pirh2 in the regulation of p53 and c-Myc stability and support its role as a tumor suppressor.
Optical and Electronic Approaches to Restoration of Sight to the Blind (2013)

Retinal degeneration leads to blindness due to loss of photoreceptors. I will review current approaches to restoration of sight based on optical and electrical stimulation of the inner retinal neurons, their achievements, challenges and perspectives.
Advancing Critical Chemical Processes for a Sustainable Future: Challenges for Industry and the Max Planck–Cardiff Centre on the Fundamentals of Heterogeneous Catalysis (FUNCAT) (2022)

Abstract Catalysis is involved in around 85 % of manufacturing industry and contributes an estimated 25 % to the global domestic product, with the majority of the processes relying on heterogeneous catalysis. Despite the importance in different global segments, the fundamental understanding of heterogeneously catalysed processes lags substantially behind that achieved in other fields. The newly established Max Planck–Cardiff Centre on the Fundamentals of Heterogeneous Catalysis (FUNCAT) targets innovative concepts that could contribute to the scientific developments needed in the research field to achieve net zero greenhouse gas emissions in the chemical industries. This Viewpoint Article presents some of our research activities and visions on the current and future challenges of heterogeneous catalysis regarding green industry and the circular economy by focusing explicitly on critical processes. Namely, hydrogen production, ammonia synthesis, and carbon dioxide reduction, along with new aspects of acetylene chemistry.
A microcomputer-based control and simulation of an advanced IPM (Interior Permanent Magnet) synchronous machine drive system for electric vehicle propulsion (1987)

Advanced digital control and computer-aided control system design techniques are playing key roles in the complex drive system design and control implementation. The paper describes a high performance microcomputer-based control and digital simulation of an inverter-fed interior permanent magnet (IPM) synchronous machine which uses Neodymium-Iron-Boron magnet. The fully operational four-quadrant drive system includes constant-torque region with zero speed operation and high speed field-weakening constant-power region. The control uses vector or field-oriented technique in constant-torque region with the direct axis aligned to the stator flux, whereas the constant-power region control is based on torque angle orientation of the impressed square-wave voltage. All the key feedback signals for the control are estimated with precision. The drive system is basically designed with an outer torque control loop for electric vehicle appliation, but speed and position control loops can be added for other industrial applications. The distributed microcomputer-based control system is based on Intel-8096 microcontroller and Texas Instruments TMS32010 type digital signal processor. The complete drive system has been simulated using the VAX-based simulation language SIMMON to verify the feasibility of the control laws and to study the performances of the drive system. The simulation results are found to have excellent correlation with themore » laboratory breadboard tests. 19 refs., 14 figs., 5 tabs.« less
SMARCA2-deficiency confers sensitivity to targeted inhibition of SMARCA4 in esophageal squamous cell carcinoma cell lines (2019)

SMARCA4/BRG1 and SMARCA2/BRM, the two mutually exclusive catalytic subunits of the BAF complex, display a well-established synthetic lethal relationship in SMARCA4-deficient cancers. Using CRISPR-Cas9 screening, we identify SMARCA4 as a novel dependency in SMARCA2-deficient esophageal squamous cell carcinoma (ESCC) models, reciprocal to the known synthetic lethal interaction. Restoration of SMARCA2 expression alleviates the dependency on SMARCA4, while engineered loss of SMARCA2 renders ESCC models vulnerable to concomitant depletion of SMARCA4. Dependency on SMARCA4 is linked to its ATPase activity, but not to bromodomain function. We highlight the relevance of SMARCA4 as a drug target in esophageal cancer using an engineered ESCC cell model harboring a SMARCA4 allele amenable to targeted proteolysis and identify SMARCA4-dependent cell models with low or absent SMARCA2 expression from additional tumor types. These findings expand the concept of SMARCA2/SMARCA4 paralog dependency and suggest that pharmacological inhibition of SMARCA4 represents a novel therapeutic opportunity for SMARCA2-deficient cancers.
Conventional and organic cropping systems at Suitia VI: Insect populations in barley (1990)

In 1988, insects were sampled from tillers and by pitfall trapping in a long-term field experiment consisting of plots of organic and conventional barley. The organic crops suffered from lack of nitrogen and from draught stress, and growth and development were retarded. The stand characteristics were suggested to be the major determinants of the fourfold higher densities of Rhopalosiphum padi(L.) (Horn., Aphididae) and the 50 % lower densities of Frankliniella tenuicornis Uzel (Thys., Thripidae) in the conventional than in the organic barley. The 75 % lower catch rate of Bembidion spp. (Col., Carabidae) in the conventional barley was attributed to lower activity resulting from the more closed canopy and more dense crop. However, the effect of an aphicide applied to the conventional crop was confounded with the true habitat effects. The densities of Coccinella seplempunclata L. (Col., Coccinellidae) were almost three times higher in the conventional than in the organic barley, which in turn was attributed to the higher prey (aphid) densities.
Complete sequence and gene analysis of a cryptic plasmid pLU4 in Lactobacillus reuteri strain LU4 (KCTC 12397BP) (2017)

A cryptic plasmid, pLU4, was isolated and sequenced from Lactobacillus reuteri strain LU4, a probiotic strain isolated from human feces in Korea. pLU4 was 33,411 bp in size with a G + C content of 40.1% and contained 41 putative open reading frames (ORFs) of more than 120 bp. Functions were assigned to 24 of these ORFS by a homologous sequence search and domain characterization, and the rest were annotated as conserved hypothetical proteins or hypothetical proteins, based on highly similar proteins found in other Lactobacillus species. A region encoding a cluster of conjugative transfer genes (trs or tra) in pLU4 showed high similarity and co-linearity with the trs region of plca36 and tra region of pLgLA39 from L. casei str. Zhang and L. gasseri, respectively. This is the first report of a trs cluster sequence from plasmids found in L. reuteri species. Comparative gene analysis revealed that pLU4 also encodes highly conserved genes for plasmid replication and stability found in several other Lactobacillus plasmids, indicating that plasmids from the genus Lactobacillus may contribute to horizontal gene transfer and adaptation to the environment. The findings of this study provide important information about these industrially relevant phenotypes and give insight into the structure, function, and evolution of large Lactobacillus conjugative plasmids.
Implementation of AC analysis using an iterative method in the 2D device simulator HFIELDS (2002)

This paper presents SOR method for small signal AC analysis, which is implemented in the HFIELDS-2D simulator. Results obtained using SOR method will be compared with an exact method which solves the same problem.
Identification of Domains within Megalomicin and Erythromycin Polyketide Synthase Modules Responsible for Differences in Polyketide Production Levels in Escherichia coli (2004)

The megalomicin and erythromycin polyketide synthases (PKSs) produce the same aglycon product, 6-deoxyerythronolide B (6-dEB). Both PKSs were examined in an Escherichia coli strain metabolically engineered to support complex polyketide biosynthesis. Production of 6-dEB in shake flask fermentations was undetectable by mass spectrometry in the strain expressing the megalomicin (Meg) PKS genes, whereas 31 mg/L 6-dEB was produced by the strain with the erythromycin (DEBS) PKS. The genes for each of the three subunits comprising the PKSs were expressed in different combinations from three compatible expression vectors (e.g., DEBS1, DEBS2, and MegA3) to identify two Meg PKS subunits, MegA1 and MegA3, which conferred lower 6-dEB titers than their DEBS counterparts. Comparison of protein expression levels and 6-dEB titers by engineered hybrid DEBS/Meg PKS genes further defined regions within modules 2 and 6 of MegA1 and MegA3, respectively, which limit protein expression and 6-dEB production in E. coli. Meg module 2 + TE (M2 + TE) and a hybrid DEBS M2/Meg M2 + TE protein were engineered and purified for in vitro comparisons with DEBS M2 + TE. The specific activity of the hybrid M2 + TE was approximately 16-fold lower than DEBS M2 + TE and only twice as high as the Meg M2 + TE enzyme in diketide elongation assays. Since the hybrid M2 worked comparably to DEBS M2 in vivo, this suggests that boosting subunit concentration could serve as a useful approach to overcome enzyme deficiencies in heterologous polyketide production.
Dynamic Impact Testing and Model Development in Support of NASA’s Advanced Composites Program (2018)

The purpose of this paper is to provide an executive overview of the HEDI effort for NASA's Advanced Composites Program and establish the foundation for the remaining papers to follow in the 2018 SciTech special session NASA ACC High Energy Dynamic Impact. The paper summarizes the work done for the Advanced Composites Program to advance our understanding of the behavior of composite materials during high energy impact events and to advance the ability of analytical tools to provide predictive simulations. The experimental program carried out at GRC is summarized and a status on the current development state for MAT213 will be provided. Future work will be discussed as the HEDI effort transitions from fundamental analysis and testing to investigating sub-component structural concept response to impact events.
Al-2.19 Chromophore (2021)

As increasingly smaller molecular materials and material structures are devised or developed for technological applications, the demands on the processes of lithography now routinely include feature sizes that are of the order of 10 nm. In reaching such a fine level of resolution, the methods of lithography have increased markedly in sophistication and brought into play 2terminology that is unfamiliar, on the one hand, to scientists tasked with the development of new lithographic materials or, on the other, to the engineers who design and operate the complex equipment that is required in modern-day processing. Publications produced by scientists need to be understood by engineers and vice versa, and these commonly arise from collaborative research that draws heavily on the terminology of two or more of the traditional disciplines. It is developments in polymer science and material science that lead progress in areas that cross traditional boundaries, such as microlithography. This document provides the exact definitions of a selection of unfamiliar terms that researchers and practitioners from different disciplines might encounter.
Mechanical Reinforcement of Epoxy with Self-Assembled Synthetic Clay in Smectic Order (2014)

Epoxy films containing self-assembled 2D colloidal α-zirconium phosphate nanoplatelets (ZrP) in smectic order were prepared using a simple, energy-efficient fabrication process suitable to industrial processing. The ZrP nanoplatelets form a chiral smectic mesophase with simultaneous lamellar order and helical arrangements in epoxy. The epoxy nanocomposite films are transparent and flexible and exhibit exceptionally high tensile modulus and strength. The findings have broad implications for development of multifunctional materials for engineering applications.
Anti‐βc mAb CSL311 inhibits human nasal polyp pathophysiology in a humanized mouse xenograft model (2019)

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Electrocardiographic measures of left ventricular hypertrophy show greater heritability than echocardiographic left ventricular mass (2002)

Genetic factors may explain a substantial proportion of variability in quantitative electrocardiographic and echocardiographic measures of left ventricular hypertrophy. The greater heritability of Sokolow-Lyon voltage suggests that electrocardiographic phenotypes may be particularly important for the molecular investigation of the genetic susceptibility to cardiac hypertrophy.
Adhesion and Adhesion Distribution in a Model Toner System (2009)

In this work, we report the use of a micro-cantilever to measure the rolling resistance of toner particles on a silicon wafer, as a mean to model the Van Waals adhesion between a toner particle and a surface. Results show that there exists a distribution of adhesion in a given toner sample. For a batch of well-blended toner with 100% surface additive coverage, we observe relatively low adhesion with a narrow distribution of adhesion, which is in contrast to the base polymer particle where the adhesion is high and the distribution is broad. For toner with 10% surface area coverage, we observe a very broad distribution of adhesion. The adhesion ranges from high, comparable to the base polymer, to low, comparable to a toner with 100% additive coverage. The results suggest that there is a variation of adhesion on the toner surface for toner with &lt;100% surface area coverage. When the additive covered toner surface is landed on the Si wafer, low adhesion is resulted. When the bare toner surface is landed on the Si wafer, relatively high adhesion is obtained. The use of this rolling resistance technique to determine the distribution of adhesion within a toner sample is discussed.
A 28.3 mW PA-Closed Loop for Linearity and Efficiency Improvement Integrated in a $+$27.1 dBm WCDMA CMOS Power Amplifier (2012)

A wideband feedback linearization technique for a power amplifier (PA), PA-closed loop, is presented. In order to achieve wideband operation, it employs a two-path feedback scheme where the input and output phases and amplitudes are detected at RF and compared to directly control and linearize the PA. The wideband characteristic of the loop suppressed the adjacent channel leakage ratio (ACLR) for WCDMA standard by 6 dB. The advantage of the feedback is demonstrated by measuring the performance against the load variation. The required back-off is degraded by only 1 dB with a voltage standing wave ratio (VSWR) of 1.5, whereas it is 3 dB without the loop. The loop consumes 28.3 mW and it reduces the quiescent power consumption of the PA by 78 mW. The chip, which integrates the loop and PA, is fabricated in a 0.13 μm CMOS technology and the loop occupies 0.3 mm by 0.7 mm. The PA delivers WCDMA output power of 27.1 dBm with a power added efficiency (PAE) of 28% and ACLR of 40 dBc. This topology makes possible the wideband feedback linearization of a watt-level PA.
General and Direct Method for Preparing Oligonucleotide-Functionalized Metal-Organic Framework Nanoparticles* (2020)

Metal-organic frameworks (MOFs) are a class of modular, crystalline, and porous materials that hold promise for storage and transport of chemical cargoes. Though MOFs have been studied in bulk forms, ways of deliberately manipulating the external surface functionality 672of MOF nanoparticles are less developed. A generalizable approach to modify their surfaces would allow one to impart chemical functionality onto the particle surface that is independent of the bulk MOF structure. Moreover, the use of a chemically programmable ligand, such as DNA, would allow for the manipulation of interparticle interactions. Herein, we report a coordination chemistry-based strategy for the surface functionalization of the external metal nodes of MOF nanoparticles with terminal phosphate-modified oligonucleotides. The external surfaces of nine distinct archetypical MOF particles containing four different metal species (Zr, Cr, Fe, and Al) were successfully functionalized with oligonucleotides, illustrating the generality of this strategy. By taking advantage of the programmable and specific interactions of DNA, 11 distinct MOF particle–inorganic particle core–satellite clusters were synthesized. In these hybrid nanoclusters, the relative stoichiometry, size, shape, and composition of the building blocks can all be independently controlled. This work provides access to a new set of nucleic acid–nanoparticle conjugates, which may be useful as programmable material building blocks and as probes for measuring and manipulating intracellular processes.
Geological Models (2011)

A smart and accurate representation of geology is a key stage for obtaining, from the modelling process, reliable results on which costly investments can be decided. First of all, the predictive value of the model is strongly dependent on the quality of the general architecture of the model. Stacking pattern analysis on cores and logs wells data help to identify the significant sedimentary surfaces –sequence boundaries, maximum flooding surfaces - that bound the stratigraphic sequences. Sequence stratigraphy controls correlations from well-to-well, but also the stratigraphic architecture and sedimentary cycle development that drive the facies distribution in the reservoir. Obviously, stratigraphic units at reservoir scale give the main features for model layering, together with the identification of flow units, vertical permeability barriers, and well completions.
Equilibrium Exchange Processes of the Aqueous Tryptophan Dipeptide (2009)

The tryptophan dipeptide (NATMA) in D2O shows two conformers having distinctive acetyl end amide-I' transition frequencies. In 2D echo spectroscopy, cross peaks between these conformer transitions are used to show that they are undergoing exchange on the 1.5 ps time scale. Simulations suggest that the accessibility of the amide group to water is restricted in one of the conformations.
Simian Immunodeficiency Virus Infection of Chimpanzees (2005)

Simian immunodeficiency viruses (SIVs) are primate lentiviruses that infect no fewer than 36 different nonhuman primate species in sub-Saharan Africa ([4][1], [9][2], [62][3]). Two of these viruses, SIVcpz from chimpanzees ( Pan troglodytes ) and SIVsmm from sooty mangabeys ( Cercocebus atys ), have
Discovery of New Chemical Leads for Prostaglandin D2 Receptor Antagonists. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Competition between engrams influences fear memory formation and recall (2016)

Collections of cells called engrams are thought to represent memories. Although there has been progress in identifying and manipulating single engrams, little is known about how multiple engrams interact to influence memory. In lateral amygdala (LA), neurons with increased excitability during training outcompete their neighbors for allocation to an engram. We examined whether competition based on neuronal excitability also governs the interaction between engrams. Mice received two distinct fear conditioning events separated by different intervals. LA neuron excitability was optogenetically manipulated and revealed a transient competitive process that integrates memories for events occurring closely in time (coallocating overlapping populations of neurons to both engrams) and separates memories for events occurring at distal times (disallocating nonoverlapping populations to each engram).
The application of cell‐based label‐free technology in drug discovery (2008)

Cell-based assays are an important part of the drug discovery process allowing for interrogation of targets and pathways in a more physiological setting compared to biochemical assays. One of the main hurdles in the cell-based assay field is to design sufficiently robust assays with adequate signal to noise parameters while maintaining the inherent physiology of the pathway or target being investigated. Conventional label and reporter-based cell assays may be more prone to artifacts due to considerable manipulation of the cell either by the label or over-expression of targets or reporter proteins. Cell-based label-free technologies preclude the need for cellular labeling or over-expression of reporter proteins, utilizing the inherent morphological and adhesive characteristics of the cell as a physiologically relevant and quantitative readout for various cellular assays. Furthermore, these technologies utilize non-invasive measurements allowing for time resolution and kinetics in the assay. In this article, we have reviewed the various label-free technologies that are being used in drug discovery settings and have focused our discussion on impedance-based label-free technologies and its main applications in drug discovery.
Coherent Receiver Based on a Broadband Optical Phase-Lock Loop (2007)

We propose and demonstrate a 1.45GHz bandwidth optical phase-lock loop receiver for linear optical phase demodulation. Using the receiver in a link application, a spurious free dynamic range of 125 dBHz2/3is measured at 300MHz.
Neural Cross-Lingual Coreference Resolution and its Application to Entity Linking (2018)

We propose an entity-centric neural cross-lingual coreference model that builds on multi-lingual embeddings and language-independent features. We perform both intrinsic and extrinsic evaluations of our model. In the intrinsic evaluation, we show that our model, when trained on English and tested on Chinese and Spanish, achieves competitive results to the models trained directly on Chinese and Spanish respectively. In the extrinsic evaluation, we show that our English model helps achieve superior entity linking accuracy on Chinese and Spanish test sets than the top 2015 TAC system without using any annotated data from Chinese or Spanish.