gebhart/patrepeval huggingface dataset:
Nitrogenase Reveals Its Inner Secrets (2002)

Nitrogen-fixing bacteria contain the enzyme nitrogenase that enables them to convert atmospheric nitrogen into ammonia, which can then be used by plants for growth. In a Perspective,
 Smith
 discusses a new structural analysis of the MoFe protein of nitrogenase, which reveals the existence of an interstitial atom in the active site that may be nitrogen. This unexpected finding could help chemists to design a more efficient method for producing ammonia from atmospheric nitrogen.
Inhibition of graft-versus-host disease. Use of a T cell-controlled suicide gene (1997)

Graft-vs-host disease (GVHD) after allogeneic bone marrow transplantation is associated with significant morbidity and mortality. T cell depletion of the marrow graft, which is currently used to prevent GVHD, has been shown to result in increased graft failure and leukemia relapse. To explore the feasibility of controlling GVHD, transgenic mice with the herpes simplex virus thymidine kinase suicide gene linked to the IL-2 promoter were used as a source of T cells to induce GVHD, which would be modulated with ganciclovir. Injection of herpes simplex virus thymidine kinase transgenic B10.A(5R) spleen cells into lethally irradiated DBA/2 mice resulted in severe acute GVHD. Treatment of the recipient mice with ganciclovir significantly inhibited GVHD-mediated weight loss and mortality and reduced the severity of inflammation in the target organs of GVHD.
p21ras links Fc ε RI to NF-AT family member in mast cells. The AP3-like factor in this cell type is an NF-AT family member (1995)

Very recently, an AP3-like transcription factor regulating the chemokine gene MARC and an NF-AT family member regulating IL-5 were the first components of the transcription factor repertoire to be described as activated in mast cells after an allergic triggering. In this study, we show that with respect to cross-competition in a gel shift analysis using an NF-AT consensus oligonucleotide binding site, the antigenicity to a recently generated serum against T cell NF-AT, and the sensitivity to macrolide immunosuppressants, the AP3-like activity on the MARC promoter is indistinguishable from that described for NF-AT in T cells. Additionally, we show that this factor functions on the MARC chemokine promoter without the AP1 cofactor, a situation reminiscent of the function of NF-AT in Th2-type T cells. In all of these aspects, and strengthened further by a gel shift competition analysis, the AP3-like transcription factor is identical to the NF-AT family member recently described by an analogous set of experiments as regulating IL-5 in mast cells. Our finding that p21ras, but probably not protein kinase C, is necessary to activate this factor after Fc epsilon RI triggering indicates a situation in which a common transcription factor denominator in mast cells induces chemokine (MARC) and lymphokine (IL-5) gene expression in a manner closely similar to Th2-type T cells, which are induced along the ras/raf signal pathway.
Behavioural specification using XML (2003)

Active networks are an example of a wide area distributed system. The objects in this system require platform independent machine-readable, flexible behaviour specifications. Current mechanisms in CORBA, DCOM and similar technologies are not adequate. We demonstrate for the first time how specifications with the required properties can be written in XML, the new language of the WWW.
P/sup 2/ codes: pragmatic trellis codes utilizing punctured convolutional codes (2002)

A pragmatic approach to trellis codes is described whereby the core of the trellis decoder is a Viterbi decoder for punctured versions of the de facto standard, rate 1/2, 64, convolutional code.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Human Arylamine N -Acetyltransferase Genes: Isolation, Chromosomal Localization, and Functional Expression (1990)

N-Acetylation by hepatic arylamine N-acetyltransferase (NAT, EC 2.3.1.5) is a major route in the metabolism and detoxification of numerous drugs and foreign chemicals. NAT is the target of a common genetic polymorphism of clinical relevance in human populations. We have used our recently isolated rabbit cDNA rnat to clone three human NAT genes from human leukocyte DNA. None of the three genomic coding sequences was interrupted by introns. Two genes, designated NAT1 and NAT2, each possessed open reading frames of 870 bp. Both genes have been assigned to human chromosome 8, pter-q11. Following transfection they were transiently expressed in monkey kidney COS-1 cells. NAT1 and NAT2 gave rise to functional NAT proteins, as judged by their NAT enzyme activity with the arylamine substrate sulfamethazine. Western blots with NAT-specific antisera detected proteins of apparent molecular weight of 33 and 31 kD in NAT1- and NAT2-transfected cultures, respectively. The product of NAT2 had an identical apparent molecular weight as that of NAT detected in human liver cytosol. The deduced amino acid sequence of NAT2 also contained 6 peptide sequences which had previously been determined from tryptic peptides of the polymorphic NAT purified from human liver. These data suggest that NAT2 encodes the polymorphic NAT protein. The third gene, NATP, had multiple deleterious mutations and did not encode a functional NAT protein; it most likely represents a pseudogene.
Self-Assembled “Dock and Lock” System for Linking Payloads to Targeting Proteins (2006)

Random conjugation of therapeutic or diagnostic payloads to targeting proteins generates functionally heterogeneous products. Conjugation of payloads to an adapter that binds to a peptide tag engineered into a targeting protein provides an alternative strategy. To progress into clinical development, an adapter/docking tag system should include humanized components and be stable in circulation. We describe here an adapter/docking tag system based on mutated fragments of human RNase I that spontaneously bind to each other and form a conjugate with a disulfide bond between complimentary cysteine residues. This self-assembled "dock and lock" system utilizes the previously described fusion C-tag, a 1-15 aa fragment of human RNase I with the R4C amino acid substitution, and a newly engineered adapter protein (Ad-C), a 21-127-aa fragment of human RNase I with the V118C substitution. Two vastly different C-tagged recombinant proteins, human vascular endothelial growth factor (VEGF) and a 254-aa long N-terminal fragment of anthrax lethal factor (LFn), retain functional activities after spontaneous conjugation of Ad-C to N-terminal or C-terminal C-tag, respectively. Ad-C modified with pegylated phospolipid and inserted into the lipid membrane of drug-loaded liposomes (Doxil) retained the ability to conjugate C-tagged proteins, yielding targeted liposomes decorated with functionally active proteins. To further optimize the system, we engineered an adapter with an additional cysteine residue at position 88 for site-specific modification, conjugated it to C-tagged VEGF, and labeled with a near-infrared fluorescent dye Cy5.5, yielding a unique functionally active probe for in vivo molecular imaging. We expect that this self-assembled "dock and lock" system will provide new opportunities for using functionally active proteins for biomedical purposes.
Membrane disrupting antimicrobial peptide dendrimers with multiple amino termini (2011)

Antimicrobial peptide dendrimer H1 Leu8(Lys-Leu)4(Lys-Phe)2Lys-LysNH2 (Lys = branching lysine) was identified by screening a 6750-membered combinatorial library by the bead-diffusion assay. Sequence variations also revealed dendrimer bH1 Leu8(Dap-Leu)4(Dap-Phe)2Dap-LysNH2 (Dap = branching 2,3-diaminopropanoic acid) as a more potent analog. H1 and bH1 showed good antimicrobial activities mediated by membrane disruption (MIC = 2–4 μg mL−1 on Bacillus subtilis and Escherichia coli) but low hemolytic activity (MHC = 310 μg mL−1 respectively >2000 μg mL−1).
Human skin interactive self-powered wearable piezoelectric bio-e-skin by electrospun poly-l-lactic acid nanofibers for non-invasive physiological signal monitoring (2017)

Flexible and wearable piezoelectric bio e-skin (PBio-e-skin) based on electrospun poly(l-lactic acid) PLLA nanofiber membrane is demonstrated for non-invasive human physiological signal monitoring and detecting dynamic tactile stimuli. The molecular orientations of the C[double bond, length as m-dash]O dipoles by electrospinning technique result in a longitudinal piezoelectric charge co-efficient (d<sub>33</sub>) value of ∼(3 ± 1) pm V<sup>-1</sup> realized by piezoresponse force microscopy, allowing the PBio-e-skin for pressure sensing applications. The robust mechanical strength (Young's modulus ∼50 MPa) of nanofiber membrane ensures PBio-e-skin's superior operational stability over 375 000 cycles. Owing to the superior mechanosensitivity of ∼22 V N<sup>-1</sup>, PBio-e-skin has the ability to measure subtle movement of muscle in the internal organs such as esophagus, trachea, motion of joints and arterial pressure by recognition of strains on human skin. This flexible and light weight PBio-e-skin precisely detects vital signs and provides important clinical insights without using any external power source. Eventually, the low cost, environmental friendly PBio-e-skin will have a huge impact in a broad range of applications including self-powered wearable health care systems, human-machine interfacing devices, artificial intelligence and prosthetic skin.
Værdi er ikke noget, der popper op i en pop-up: Det er noget, vi skaber sammen (2016)

Et kvalitativt studie af hvordan værdi skabes gennem konsumering af<br/>kommercielle pop-up aktiviteter set fra moderne forbrugeres synspunkt.
An Investigation on Electrorheological Fluid-assisted Polishing Process for Tungsten Carbide (2012)

The surface roughness and material removal is investigated in electrorheological (ER) fluid-assisted polishing of tungsten carbide die. In this study, the microstructure of fibrous columns formed by particles perpendicular to the electrodes is observed by CCD when the electrical field is applied. The distribution of the electric field strength on the surface of workpiece was analyzed by ANSYS and theoretical equation. The force acting on ER particles and abrasive particles is calculated in an electric field. According to Preston’s equation, a model for material removal of the polished conductive workpiece is derived. Polishing experiments with Al2O3 and diamond particles for tungsten carbide is conducted. The influential regularities of the polishing time, rotational speed of micro-tool, voltage, concentrations of abrasive particles and gap of electrodes on the surface roughness and material removal are obtained. The profile of machined area is measured by WYKO and the experimental results are compared with the theoretical predictions, which confirm the validity of the presented model.
Structural Evidence of Functional Divergence in Human Alkaline Phosphatases (2002)

The evolution of the alkaline phosphatase (AP) gene family has lead to the existence in humans of one tissue-nonspecific (TNAP) and three tissue-specific isozymes, i.e. intestinal (IAP), germ cell (GCAP), and placental AP (PLAP). To define the structural differences between these isozymes, we have built models of the TNAP, IAP, and GCAP molecules based on the 1.8-structure of PLAP(1) and have performed a comparative structural analysis. We have examined the monomer-monomer interface as this area is crucial for protein stability and enzymatic activity. We found that the interface allows the formation of heterodimers among IAP, GCAP, and PLAP but not between TNAP with any of the three tissue-specific isozymes. Secondly, the active site cleft was mapped into three regions, i.e. the active site itself, the roof of the cleft, and the floor of the cleft. This analysis led to a structural fingerprint of the active site of each AP isozyme that suggests a diversification in substrate specificity for this isozyme family.
Recombinant Immunomodulating Lentogenic or Mesogenic Oncolytic Newcastle Disease Virus for Treatment of Pancreatic Adenocarcinoma (2015)

Oncolytic Newcastle disease virus (NDV) might be a promising new therapeutic agent for the treatment of pancreatic cancer. We evaluated recombinant NDVs (rNDVs) expressing interferon (rNDV-hIFNβ-F₀) or an IFN antagonistic protein (rNDV-NS1-F₀), as well as rNDV with increased virulence (rNDV-F₃aa) for oncolytic efficacy in human pancreatic adenocarcinoma cells. Expression of additional proteins did not hamper virus replication or cytotoxic effects on itself. However, expression of interferon, but not NS1, resulted in loss of multicycle replication. Conversely, increasing the virulence (rNDV-F₃aa) resulted in enhanced replication of the virus. Type I interferon was produced in high amounts by all tumor cells inoculated with rNDV-hIFNβ -F₀, while inoculation with rNDV-NS1-F₀ resulted in a complete block of interferon production in most cells. Inoculation of human pancreatic adenocarcinoma cells with rNDV-F₃aa caused markedly more cytotoxicity compared to rNDV-F₀, while inoculation with rNDVβ-hIFN -F₀ and rNDV-NS1-F₀ induced cytotoxic effects comparable to those induced by the parental rNDV-F₀. Evaluation in vivo using mice bearing subcutaneous pancreatic cancer xenografts revealed that only intratumoral injection with rNDV-F₃aa resulted in regression of tumors. We conclude that although lentogenic rNDVs harboring proteins that modulate the type I interferon pathway proteins do have an oncolytic effect, a more virulent mesogenic rNDV might be needed to improve oncolytic efficacy.
A method of imaging viscoelastic parameters with acoustic radiation force (2000)

Acoustic radiation force has been proposed as a method of interrogating the mechanical properties of tissue. One simple approach applies a series of focused ultrasonic pulses to generate an acoustic radiation force, then processes the echoes returned from these pulses to estimate the radiation-force-induced displacement as a function of time. This process can be repeated at a number of locations to acquire data for image formation. In previous work we have formed images of tissue stiffness by depicting the maximum displacement induced at each tissue location after a finite period of insonification. While these maximum displacement images are able to differentiate materials of disparate mechanical properties, they exploit only a fraction of the information available. In this paper we show that the time-displacement curves acquired from tissue mimicking phantoms exhibit a viscoelastic response which is accurately described by the Voigt model. We describe how the viscous and elastic parameters of this model may be determined from experimental data. Finally, we show phantom images that depict not only the maximum local displacement, but also the viscous and elastic model parameters. These images offer complementary information about the target.
NADPH Oxidase 4 (Nox4) Suppresses Mitochondrial Biogenesis and Bioenergetics in Lung Fibroblasts via a Nuclear Factor Erythroid-derived 2-like 2 (Nrf2)-dependent Pathway (2017)

Mitochondrial bioenergetics are critical for cellular homeostasis and stress responses. The reactive oxygen species-generating enzyme, NADPH oxidase 4 (Nox4), regulates a number of physiological and pathological processes, including cellular differentiation, host defense, and tissue fibrosis. In this study we explored the role of constitutive Nox4 activity in regulating mitochondrial function. An increase in mitochondrial oxygen consumption and reserve capacity was observed in murine and human lung fibroblasts with genetic deficiency (or silencing) of Nox4. Inhibition of Nox4 expression/activity by genetic or pharmacological approaches resulted in stimulation of mitochondrial biogenesis, as evidenced by elevated mitochondrial-to-nuclear DNA ratio and increased expression of the mitochondrial markers transcription factor A (TFAM), citrate synthase, voltage-dependent anion channel (VDAC), and cytochrome <i>c</i> oxidase subunit 4 (COX IV). Induction of mitochondrial biogenesis was dependent on TFAM up-regulation but was independent of the activation of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α). The enhancement of mitochondrial bioenergetics as well as the increase in mitochondrial proteins in Nox4-deficient lung fibroblasts is inhibited by silencing of nuclear factor erythroid-derived 2-like 2 (Nrf2), supporting a key role for Nrf2 in control of mitochondrial biogenesis. Together, these results indicate a critical role for both Nox4 and Nrf2 in counter-regulation of mitochondrial biogenesis and metabolism.
Threefold Increase in the Young’s Modulus of Graphite Negative Electrode during Lithium Intercalation (2010)

Density functional theory (DFT) is used to reveal that the polycrystalline Young's modulus of graphite triples as it is lithiated to . This behavior is captured in a linear relationship between and lithium concentration suitable for continuum-scale models aimed at predicting diffusion-induced deformation in battery electrode materials. Alternatively, Poisson's ratio is concentration-independent. Charge-transfer analyses suggest simultaneous weakening of carbon–carbon bonds within graphite basal planes and strengthening of interlayer bonding during lithiation. The variation in bond strength is shown to be responsible for the differences between elasticity tensor components, , of lithium–graphite intercalation (Li-GIC) phases. Strain accumulation during Li intercalation and deintercalation is examined with a core–shell model of a Li-GIC particle assuming two coexisting phases. The requisite force equilibrium uses different Young's moduli computed with DFT. Lithium-poor phases develop tensile strains, whereas Li-rich phases develop compressive strains. Results from the core–shell model suggest that elastic strain should be defined relative to the newest phase that forms during lithiation of graphite, and Li concentration-dependent mechanical properties should be considered in continuum level models.
Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells (2017)

Interleukin-2 (IL-2) is an established therapeutic agent used for cancer immunotherapy. Since treatment efficacy is mediated by CD8<sup>+</sup> and NK cell activity at the tumour site, considerable efforts have focused on generating variants that expand these subsets systemically, as exemplified by IL-2/antibody complexes and 'superkines'. Here we describe a novel determinant of antitumour activity using fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc) region. Generation of long-lived IL-2-Fc variants in which CD25 binding is abolished through mutation effectively prevents unwanted activation of CD25<sup>+</sup> regulatory T-cells (Tregs) and results in strong expansion of CD25<sup>-</sup> cytotoxic subsets. Surprisingly, however, such variants are less effective than wild-type IL-2-Fc in mediating tumour rejection. Instead, we report that efficacy is crucially dependent on depletion of Tregs through Fc-mediated immune effector functions. Our results underpin an unexpected mechanism of action and provide important guidance for the development of next generation IL-2 therapeutics.
Aesop: A Visual Storytelling Platform for Conversational AI (2018)

We present a new collaborative visual storytelling platform, Aesop, for direction and animation. Aesop consists of a language parser, human gesture monitoring, composition graphs, dialogue state manager, and an interactive 3D animation software. Aesop thus enables 3D spatial and temporal reasoning which are both essential for storytelling. Our key innovation is to enable conversational AI using both verbal and non-verbal communication, which enables research in language, vision, and planning.
Targeted Disruption of Gb3/CD77 Synthase Gene Resulted in the Complete Deletion of Globo-series Glycosphingolipids and Loss of Sensitivity to Verotoxins (2006)

To examine whether globotriaosylceramide (Gb3/CD77) is a receptor for verotoxins (VTs) in vivo, sensitivity of Gb3/CD77 synthase null mutant mice to VT-2 and VT-1 was analyzed. Although wild-type mice died after administration of 0.02 microg of VT-2 or 1.0 microg of VT-1, the mutant mice showed no reaction to doses as much as 100 times that administered to wild types. Expression analysis of Gb3/CD77 in mouse tissues with antibody revealed that low, but definite, levels of Gb3/CD77 were expressed in the microvascular endothelial cells of the brain cortex and pia mater and in renal tubular capillaries. Corresponding to the Gb3/CD77 expression, tissue damage with edema, congestion, and cytopathic changes was observed, indicating that Gb3/CD77 (and its derivatives) exclusively function as a receptor for VTs in vivo. The lethal kinetics were similar regardless of lipopolysaccharide elimination in VT preparation, suggesting that basal Gb3/CD77 levels are sufficient for lethal effects of VTs.
FoxM1B Regulates NEDD4-1 Expression, Leading to Cellular Transformation and Full Malignant Phenotype in Immortalized Human Astrocytes (2010)

Our recent studies have shown that the FoxM1B transcription factor is overexpressed in human glioma tissues and that the level of its expression correlates directly with glioma grade. However, whether FoxM1B plays a role in the early development of glioma (i.e., in transformation) is unknown. In this study, we found that the FoxM1B molecule causes cellular transformation and tumor formation in normal human astrocytes (NHA) immortalized by p53 and pRB inhibition. Moreover, brain tumors that arose from intracranial injection of FoxM1B-expressing immortalized NHAs displayed glioblastoma multiforme (GBM) phenotypes, suggesting that FoxM1B overexpression in immortalized NHAs not only transforms the cells but also leads to GBM formation. Mechanistically, our results showed that overexpression of FoxM1B upregulated NEDD4-1, an E3 ligase that mediates the degradation and downregulation of phosphatase and tensin homologue (PTEN) in multiple cell lines. Decreased PTEN in turn resulted in the hyperactivation of Akt, which led to phosphorylation and cytoplasmic retention of FoxO3a. Blocking Akt activation with phosphoinositide 3-kinase/Akt inhibitors inhibited the FoxM1B-induced transformation of immortalized NHAs. Furthermore, overexpression of FoxM1B in immortalized NHAs increased the expression of survivin, cyclin D1, and cyclin E, which are important molecules for tumor growth. Collectively, these results indicate that overexpression of FoxM1B, in cooperation with p53 and pRB inhibition in NHA cells, promotes astrocyte transformation and GBM formation through multiple mechanisms.
Wideband fibre dispersion equalisation up to fourth-order for long-distance sub-picosecond opticalpulse transmission (1999)

The authors demonstrate wideband dispersion compensation of a 85 km fibre link up to the fourth-order. The second-order and third-order dispersions of a standard singlemode fibre are simultaneously compensated for by a dispersion-compensation fibre, and the residual third-order dispersion and the fourth-order dispersion are precisely equalised by a frequency-resolved programmable dispersion compensator. A dispersion window wider than 30 nm is realised, and 0.2 ps pulse trains with 22 nm bandwidth can be transmitted with small dispersive distortion.