gebhart/patrepeval huggingface dataset:
A role for <i>Toxoplasma gondii</i> chloroquine resistance transporter in bradyzoite viability and digestive vacuole maintenance (2019)

ABSTRACT Toxoplasma gondii is a ubiquitous pathogen that can cause encephalitis, congenital defects, and ocular disease. T. gondii has also been implicated as a risk factor for mental illness in humans. The parasite persists in the brain as slow growing bradyzoites contained within intracellular cysts. No treatments exist to eliminate this form of parasite. Although proteolytic degradation within the parasite lysosomal-like vacuolar compartment (VAC) is critical for bradyzoite viability, whether other aspects of the VAC are important for parasite persistence remains unknown. An ortholog of Plasmodium falciparum CRT has previously been identified in T. gondii (TgCRT). To interrogate the function of TgCRT in chronic stage bradyzoites and its role in persistence, we knocked out TgCRT in a cystogenic strain and assessed VAC size, VAC digestion of host-derived proteins and parasite autophagosomes, and viability of in vitro and in vivo bradyzoites. We found that whereas parasites deficient in TgCRT exhibit normal digestion within the VAC, they display a markedly distended VAC and their viability is compromised both in vitro and in vivo . Interestingly, impairing VAC proteolysis in TgCRT deficient bradyzoites restored VAC size, consistent with a role for TgCRT as a transporter of products of digestion from the VAC. In conjunction with earlier studies, our current findings suggest a functional link between TgCRT and VAC proteolysis. This work provides further evidence of a crucial role for the VAC in bradyzoite persistence and a new potential VAC target to abate chronic Toxoplasma infection. IMPORTANCE Individuals chronically infected with the intracellular parasite Toxoplasma gondii are at risk of experiencing reactivated disease that can result in progressive loss of vision. No effective treatments exist for chronic toxoplasmosis due in part to a poor understanding of the biology underlying chronic infection and a lack of well validated potential targets. Here we show that a T. gondii transporter is functionally linked to protein digestion within the parasite lysosome-like organelle and that this transporter is necessary to sustain chronic infection in culture and in experimentally infected mice. Ablating the transporter results in severe bloating of the lysosome-like organelle. Together with earlier work, this study suggests the parasite’s lysosome-like organelle is vital for parasite survival, thus rendering it a potential target for diminishing infection and reducing the risk of reactivated disease.
Mn-Doped Zn Metal–Organic Framework-Derived Porous N-Doped Carbon Composite as a High-Performance Nonprecious Electrocatalyst for Oxygen Reduction and Aqueous/Flexible Zinc–Air Batteries (2023)

Developing low-cost, efficient, and stable oxygen reduction reaction (ORR) electrocatalysts is crucial for the commercialization of energy conversion devices such as metal-air batteries. In this study, we report a Mn-doped Zn metal-organic framework-derived porous N-doped carbon composite (30-ZnMn-NC) as a high-performance ORR catalyst. 30-ZnMn-NC exhibits excellent electrocatalytic activity, demonstrating a kinetic current density of 9.58 mA cm<sup>-2</sup> (0.8 V) and a half-wave potential of 0.83 V, surpassing the benchmark Pt/C and most of the recently reported non-noble metal-based catalysts. Moreover, the assembled zinc-air battery with 30-ZnMn-NC demonstrates high peak power densities of 207 and 66.3 mW cm<sup>-2</sup> in liquid and flexible batteries, respectively, highlighting its potential for practical applications. The excellent electrocatalytic activity of 30-ZnMn-NC is attributed to its unique porous structure, the strong electronic interaction between metal Zn/Mn and adjacent N-doped carbon, as well as the bimetallic Mn/Zn-N active sites, which synergistically promote faster reaction kinetics. This work offers a controllable design strategy for efficient electrocatalysts with porous structures and bimetallic active sites, which can significantly enhance the performance of energy conversion devices.
Molecular Recognition of Human CD1b Antigen Complexes: Evidence for a Common Pattern of Interaction with αβ TCRs (2000)

Ag-specific T cell recognition is mediated through direct interaction of clonotypic TCRs with complexes formed between Ag-presenting molecules and their bound ligands. Although characterized in substantial detail for class I and class II MHC encoded molecules, the molecular interactions responsible for TCR recognition of the CD1 lipid and glycolipid Ag-presenting molecules are not yet well understood. Using a panel of epitope-specific Abs and site-specific mutants of the CD1b molecule, we showed that TCR interactions occur on the membrane distal aspects of the CD1b molecule over the alpha1 and alpha2 domain helices. The location of residues on CD1b important for this interaction suggested that TCRs bind in a diagonal orientation relative to the longitudinal axes of the alpha helices. The data point to a model in which TCR interaction extends over the opening of the putative Ag-binding groove, making multiple direct contacts with both alpha helices and bound Ag. Although reminiscent of TCR interaction with MHC class I, our data also pointed to significant differences between the TCR interactions with CD1 and MHC encoded Ag-presenting molecules, indicating that Ag receptor binding must be modified to accommodate the unique molecular structure of the CD1b molecule and the unusual Ags it presents.
A nicotinamide phosphoribosyltransferase–GAPDH interaction sustains the stress-induced NMN/NAD+ salvage pathway in the nucleus (2020)

All cells require sustained intracellular energy flux, which is driven by redox chemistry at the subcellular level. NAD<sup>+</sup>, its phosphorylated variant NAD(P)<sup>+</sup>, and its reduced forms NAD(P)/NAD(P)H are all redox cofactors with key roles in energy metabolism and are substrates for several NAD-consuming enzymes (<i>e.g.</i> poly(ADP-ribose) polymerases, sirtuins, and others). The nicotinamide salvage pathway, constituted by nicotinamide mononucleotide adenylyltransferase (NMNAT) and nicotinamide phosphoribosyltransferase (NAMPT), mainly replenishes NAD<sup>+</sup> in eukaryotes. However, unlike NMNAT1, NAMPT is not known to be a nuclear protein, prompting the question of how the nuclear NAD<sup>+</sup> pool is maintained and how it is replenished upon NAD<sup>+</sup> consumption. In the present work, using human and murine cells; immunoprecipitation, pulldown, and surface plasmon resonance assays; and immunofluorescence, small-angle X-ray scattering, and MS-based analyses, we report that GAPDH and NAMPT form a stable complex that is essential for nuclear translocation of NAMPT. This translocation furnishes NMN to replenish NAD<sup>+</sup> to compensate for the activation of NAD-consuming enzymes by stressful stimuli induced by exposure to H<sub>2</sub>O<sub>2</sub> or <i>S</i>-nitrosoglutathione and DNA damage inducers. These results indicate that by forming a complex with GAPDH, NAMPT can translocate to the nucleus and thereby sustain the stress-induced NMN/NAD<sup>+</sup> salvage pathway.
Cutting Edge: Intravenous Soluble Antigen Is Presented to CD4 T Cells by CD8− Dendritic Cells, but Cross-Presented to CD8 T Cells by CD8+ Dendritic Cells (2001)

Mouse spleen contains three distinct mature dendritic cell (DC) populations (CD4(+)8(-), CD4(-)8(-), and CD4(-)8(+)) which retain a capacity to take up particulate and soluble AGS: Although the three splenic DC subtypes showed similar uptake of injected soluble OVA, they differed markedly in their capacity to present this Ag and activate proliferation in OVA-specific CD4 or CD8 T cells. For class II MHC-restricted presentation to CD4 T cells, the CD8(-) DC subtypes were more efficient, but for class I MHC-restricted presentation to CD8 T cells, the CD8(+) DC subtype was far more effective. This differential persisted when the DC were activated with LPS. The CD8(+) DC are therefore specialized for in vivo cross-presentation of exogenous soluble Ags into the class I MHC presentation pathway.
Cadaveric Strain Gauge and Micromotion Analysis of a New Stem Design With Increased Surface Roughness of Proximal Coating (2013)

The design of the femoral prosthesis in cementless total hip arthroplasty is known to affect the initial strains in the cortex during implantation and in the early postoperative time period. High strains have a direct influence on periprosthetic fracture. This study compares the existing ABGII stem, which is proximally coated with a grit blasted titanium surface with hydroxyapatite coating with a prototype that has a rougher titanium plasma spray proximal coating. The Australian National Joint registry results 2011 reported the ABG2 femoral component cumulative percent revision (CPR) of 6.5 (93.5% survival), which compares favourably with equivalent stems with 10 year CPR data such as the Taperloc 6.6 and Corail 7.3. Six pairs of fresh-frozen cadaveric femurs were mounted in blocks according to ISO guidelines in single leg stance setup. Five strain gauges were attached around the neck of the femur and then prepared according to routine operative techniques to accept the femoral prosthesis. Cortical strains were measured during insertion of the prosthesis with an instrumented mallet attached to an accelerometer. Subsequently, force-displacement readings were taken during cyclical loading on a servo-hydraulic machine and finally the stems were tested to failure. Our results showed significantly less strain during cyclical loading of the stem with increased surface roughness (p
Pressure gradient measurement in the coronary artery using 4D PC-MRI: towards noninvasive quantification of fractional flow reserve (2014)

Background Fractional flow reserve (FFR) is an invasive procedure evaluating the functional significance of an intermediate stenosis by measurement of pressure drop across stenosis [1]. Noninvasive pressure measurement technique i.e. Phase-contrast (PC)-MRI has been studied in the cardiac chamber[2], aorta[3], and renal[4] arteries. The purpose of this study was to investigate the feasibility of pressure gradient quantification using 4DPC-MRI in the coronary arteries, which may allow for the derivation of FFR associated with stenosis.
Integrated-optical directional coupler biosensor (1996)

We present measurements of biomolecular binding reactions, using a new type of integrated-optical biosensor based on a planar directional coupler structure. The device is fabricated by Ag(+) - Na(+) ion exchange in glass, and definition of the sensing region is achieved by use of transparent fluoropolymer isolation layers formed by thermal evaporation. The suitability of the sensor for application to the detection of environmental pollutants is considered.
Electropolymerization of Aniline on Conductive Vulcanizates and Charge-Discharge Properties (1993)

Abstract To obtain electrode materials with good charge-discharge properties, the electrochemical polymerization of aniline on conductive vulcanizates containing Ketjin black was investigated along with the charge-discharge properties of these materials. When EPDM vulcanizates containing Ketjin black greater than 20 phr were used as working electrodes, the polymerization of aniline occurred easily and conductive laminates of vulcanizate and polyaniline were obtained. This required an EPDM vulcanizate conductivity of more than 0.1 S/cm. The selection of elastomers and solvents for the electrochemical reaction is important. A combination of EPDM and water solvent was found to be suitable for the electrochemical polymerization of aniline. Polyaniline products on vulcanizate electrodes had lower film densities than polypyrrole products, and exhibited greater adhesion to the vulcanizates than to Pt electrodes. Li battery cells, using these polyaniline vulcanizate electrodes, possessed remarkably higher charge-discharge capacity and greater cycles life than the polyaniline Pt electrode. The vulcanizate electrode retained good charge-discharge properties even at a current density exceeding 1.0 mA/cm 2 .
The isolation mode rejection ratio in bioelectric amplifiers (1991)

Galvanic isolation of a patient during a bioelectric recording is necessary to ensure the safety of the patient. In a typical measurement situation high interference voltages may be present across the isolation barrier. In this paper the necessity of a very high isolation mode rejection ratio--the ability of the amplifier to suppress feed-through from voltages across the isolation barrier to the output--is argued and a design of a multichannel amplifier with an isolation mode rejection ratio of 160 dB is described.
Abstract 2117: Lasonolide A-induced premature chromosome condensation is mediated by the proto-oncogene c-Raf (Raf1). (2013)

Abstract Lasonolide A (LSA) was originally identified in a screen for novel antitumor compounds from marine organisms with high and selective cytotoxicity against mesenchymal cancer cells. We recently demonstrated that LSA induces rapid and reversible premature chromosome condensation (PCC) associated with profound epigenetic alterations in different cell types, independently of cyclin-dependent kinases activation. In order to identify cellular targets involved in LSA sensitivity, we used a pool of kinases and phosphatases shRNAs in the human colon carcinoma HCT-116 cell line. Among the genes whose inactivation promotes the survival of LSA-treated cells, we observed an enrichment of genes involved in mitotic functions including Raf1, a well-known serine-threonine kinase regulating cell proliferation and survival. LSA induces the rapid and reversible phosphorylation of Raf1 on Ser338 in a time- and a dose-dependent manner. To establish a causal relationship between LSA-induced PCC and Raf1, we first used siRNA targeting Raf1. Knocking-down Raf1 decreased LSA-induced PCC. Furthermore, mouse embryonic fibroblasts depleted in Raf1 were found resistant to LSA-induced PCC. Our results suggest a novel role of Raf1 in chromatin condensation. They also demonstrate that the target of LSA affects the c-Raf pathway and a novel mechanism of action of LSA as an effective inducer of PCC and potential novel anticancer agent. Citation Format: Yong-Wei Zhang, Rozenn Josse, Arun Ghosh, Ji Luo, Yves Pommier. Lasonolide A-induced premature chromosome condensation is mediated by the proto-oncogene c-Raf (Raf1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2117. doi:10.1158/1538-7445.AM2013-2117 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Improvements of Coercivity and Corrosion Resistance in Nd-Fe-Co-B Sintered Magnet by Addition of V or Mo (1991)

The structure, magnetic properties and corrosion resistance of sintered anisotropic Nd-Dy-Fe-Co-B- (V or Mo) permanent magnets are reported. Addition of a few atomic percent V or Mo was found to be beneficial in that it enhances the intrinsic coercivity (H <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">cJ</inf> ) without significantly sacrificing the remanence or maximum energy product, especially when a substantial amount of Co (approximately 5 at%) is present. Thus the addition of V or Mo together with Co serves to improve both corrosion resistance and temperature stability of the magnetic properties. Possible reasons for the enhancement of H <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">cJ</inf> by V and Mo are also discussed.
CHAPERONE‐ASSISTED PROTEIN FOLDING IN THE CYTOSOL (2007)

The efficient folding of many newly‐synthesized proteins depends on assistance by molecular chaperones, which act to prevent protein misfolding and aggregation in the crowded environment of the cell. Nascent chain‐binding chaperones, including Trigger factor (TF) and Hsp70, stabilize elongating chains on ribosomes in a non‐aggregated state. Folding in the cytosol is achieved either on controlled chain release from these factors or following transfer of newly‐synthesized proteins to downstream chaperones, such as the cylindrical chaperonin complexes, GroEL and TRiC. The contribution of ribosome‐ and nascent chain‐binding chaperones to co‐ and post‐translational folding is not yet well understood. Recent evidence from our laboratory suggests that folding in the bacterial cytosol is geared towards a post‐translational mechanism, as a result of rapid translation speed and a delay in folding relative to translation caused by chaperones such as TF. In contrast, co‐translational and sequential domain folding are more efficiently supported by the eukaryotic translation‐chaperone machinery. We propose that this difference may have played a role in the explosive evolution of multi‐domain proteins in eukaryotes and can help explain why complex eukaryotic proteins often misfold and aggregate upon bacterial expression. Understanding the bacterial and eukaryotic translation‐folding machineries in more detail may provide the basis for engineering bacterial strains that are better adapted to the expression of eukaryotic proteins.
Phase III trial of high-dose interferon alpha-2b versus cisplatin, vinblastine, DTIC plus IL-2 and interferon in patients with high-risk melanoma (SWOG S0008): An intergroup study of CALGB, COG, ECOG, and SWOG. (2012)

8504 Background: High-dose interferon for one year (HDI) is the FDA approved adjuvant therapy for patients (pts) with high-risk melanoma (HRM). Efforts to modify IFN dose or schedule have not improved efficacy. A meta-analysis demonstrated that biochemotherapy (BCT) produced superior response rates compared with chemotherapy in pts with stage IV melanoma (Wheatley et al J Clin Oncol 25:5426, 2007). We sought to determine whether a short course of BCT would be more effective than HDI as adjuvant treatment in pts with HRM. Methods: S-0008 (an Intergroup Phase III trial) enrolled pts who were high risk (Stage III A-N2a thru Stage III C N3) and randomized them to receive either HDI or BCT consisting of dacarbazine 800 mg/m 2 day 1, cisplatin 20 mg/m 2 / days 1-4, vinblastine 1.2 mg/m 2 days 1-4, IL-2 9 MIU/m 2 /day continuous IV days 1-4, IFN 5 MU/m 2 /day sc days 1-4, 8,10,12, and G-CSF 5 ug/kg/day sc days 7-16. BCT cycles were given every 21 days x 3 cycles (9 weeks total). Pts were stratified for number of involved nodes (1-3 v ≥4), micro v macro metastasis, and ulceration of the primary. Co-primary endpoints were relapse free survival (RFS) and overall survival (OS) using a one-sided log rank test at p= 0.05. Results: 432 pts were enrolled between 8/2000 and 11/2007: 30 were ineligible or withdrew consent. Grade 3 and 4 adverse events occurred in 57% and 7% respectively of HDI pts and 36% and 40% of BCT pts. At a median f/up of 6 yrs, BCT improved RFS (p = 0.02, HR 0.77 [90% CI: 0.62 – 0.96]) with median RFS for BCT of 4.0 yrs (90% CI:1.9 – 5.9) v 1.9 yrs (90% CI: 1.4 – 2.5) and 5 yr RFS of 47% v 39%. Median OS was not different between the two arms (p = 0.49 HR 1.0 [90% CI: 0.78 – 1.27]) with median OS not yet reached for BCT v 8.4 yrs (90% CI: 4.5 – 9.3) for HDI and 5 yr survival 56% for both arms. Conclusions: In HRM pts, BCT provides a statistically significant improvement in RFS compared to HDI, but no discernable difference in OS and more grade IV toxicity. BCT represents a shorter, alternative treatment for pts with HRM, and a potential control arm and basis for future combinations in the adjuvant setting.
Evaluation of cartilage surface injuries using 3D-double echo steady state (3D-DESS): Effect of changing flip angle from 40° to 90° (2011)

In evaluating knee cartilage surface lesions with 3D-DESS sequences, a flip angle setting of 90° is more effective than the conventional setting of 40°.
Interactive modelling and tracking for mixed and augmented reality (2006)

Some tasks vital to many mixed and augmented reality systems are either too time consuming or complex to be carried out whilst the system is active. 3D scene modelling and labelling are two such tasks commonly performed by skilled operators in an off-line initialisation phase. Because this phase sometimes needs specialist software and/or expertise it can be a considerable limiting factor for new mixed reality system developers. If a mixed reality system is to operate in real-time, where artificial graphics are woven into real world live images, the way in which these off-line processes are tackled is critical. In this paper we propose a flexible new approach that reduces the time spent during the off-line initialisation phase by adopting an on-line interactive primitive modelling technique. Our solution combines two existing and freely available packages, the Augmented Reality Toolkit Plus (ARToolKitPlus) and the Mixed Reality Toolkit (MRT), to enable rapid interactive modelling over live video using a freely moving camera. As a demonstration we show how these can be used to rapidly seed an object appearance-based tracking algorithm.
Discrete-basis-set calculation for<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>e</mml:mi></mml:math>-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">N</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>scattering cross sections in the static-exchange approximation (1978)

Calculations are reported for low-energy $e$-${\mathrm{N}}_{2}$ scattering cross sections in the static-exchange approximation. Our approach involves solving the Lippman-Schwinger equation for the transition operator in a subspace of Gaussian functions. A new feature of the method is the analytical evaluation of matrix elements of the free-particle Green's function. Another development is the use of an analytical transformation to obtain single-center expansion coefficients for the scattering amplitude from our multicenter discrete-basis-set representation of the $T$ matrix. We present results for the total elastic and rotational excitation cross sections, and the momentum-transfer cross section, for incident electron energies from 0.5 to 10 eV. Comparison is made with other theoretical results and experimental data.
From the track to the ocean: Using flow control to improve marine bio-logging tags for cetaceans (2017)

Bio-logging tags are an important tool for the study of cetaceans, but superficial tags inevitably increase hydrodynamic loading. Substantial forces can be generated by tags on fast-swimming animals, potentially affecting behavior and energetics or promoting early tag removal. Streamlined forms have been used to reduce loading, but these designs can accelerate flow over the top of the tag. This non-axisymmetric flow results in large lift forces (normal to the animal) that become the dominant force component at high speeds. In order to reduce lift and minimize total hydrodynamic loading this work presents a new tag design (Model A) that incorporates a hydrodynamic body, a channel to reduce fluid speed differences above and below the housing and wing to redirect flow to counter lift. Additionally, three derivatives of the Model A design were used to examine the contribution of individual flow control features to overall performance. Hydrodynamic loadings of four models were compared using computational fluid dynamics (CFD). The Model A design eliminated all lift force and generated up to ~30 N of downward force in simulated 6 m/s aligned flow. The simulations were validated using particle image velocimetry (PIV) to experimentally characterize the flow around the tag design. The results of these experiments confirm the trends predicted by the simulations and demonstrate the potential benefit of flow control elements for the reduction of tag induced forces on the animal.