gebhart/patrepeval huggingface dataset:
Therapeutic Strategies for Immune Transformation in Parkinson’s Disease (2022)

Dysregulation of innate and adaptive immunity can lead to alpha-synuclein (α-syn) misfolding, aggregation, and post-translational modifications in Parkinson's disease (PD). This process is driven by neuroinflammation and oxidative stress, which can contribute to the release of neurotoxic oligomers that facilitate dopaminergic neurodegeneration. Strategies that promote vaccines and antibodies target the clearance of misfolded, modified α-syn, while gene therapy approaches propose to deliver intracellular single chain nanobodies to mitigate α-syn misfolding, or to deliver neurotrophic factors that support neuronal viability in an otherwise neurotoxic environment. Additionally, transformative immune responses provide potential targets for PD therapeutics. Anti-inflammatory drugs represent one strategy that principally affects innate immunity. Considerable research efforts have focused on transforming the balance of pro-inflammatory effector T cells (Teffs) to favor regulatory T cell (Treg) activity, which aims to attenuate neuroinflammation and support reparative and neurotrophic homeostasis. This approach serves to control innate microglial neurotoxic activities and may facilitate clearance of α-syn aggregates accordingly. More recently, changes in the intestinal microbiome have been shown to alter the gut-immune-brain axis leading to suppressed leakage of bacterial products that can promote peripheral inflammation and α-syn misfolding. Together, each of the approaches serves to interdict chronic inflammation associated with disordered immunity and neurodegeneration. Herein, we examine research strategies aimed at improving clinical outcomes in PD.
Digital microstructures matching statistical distributions of features in real materials – example of forgings (2010)

International audience
Acoustic actuation of bioinspired microswimmers (2016)

Acoustic actuation of bioinspired microswimmers is experimentally demonstrated. Microswimmers are fabricated in situ in a microchannel. Upon acoustic excitation, the flagellum of the microswimmer oscillates, which in turn generates linear or rotary movement depending on the swimmer design. The speed of these bioinspired microswimmers is tuned by adjusting the voltage amplitude applied to the acoustic transducer. Simple microfabrication and remote actuation are promising for biomedical applications.
Matrix Matters: novel insights for the extraction, preparation, and quantitation of microplastics in a freshwater mesocosm study (2023)

Abstract The extraction and characterization of secondary microplastics, those formed through subjection to the environment, must continuously improve in accuracy and applicability in order to generate robust microplastics exposure and risk assessments. Currently, there is a dearth of reliable extraction and quantitation methods for solid microplastic particles in sediment with chemical specificity. Herein we present advances in methodologies to extract and quantify microplastic particles from sediment, utilizing an outdoor mesocosm to model a freshwater coastal environment. Model secondary microplastics of crosslinked polyurethane (PU) were studied in comparison to model secondary polypropylene (PP) microplastics. Techniques to characterize particles in sediment included pyrolysis gas chromatography mass spectrometry (py GC/MS), stereoscope microscopy, and scanning electron microscopy. To complement particle analysis, plastic-associated leachable molecules were extracted from sediment and analyzed semi-quantitatively by high performance liquid chromatography with high-resolution mass spectrometry (HPLC/HR-MS). After developing and optimizing extraction and analytical methods we quantitated PU microparticles by count and weight and discovered that model PU particles fell from the water column into the sediment over the course of a year, while no PP particles were located in sediment samples. In addition, target small molecules associated with the crosslinked PU were identified in sediment by HPLC/HR-MS but leachable molecules associated with polypropylene could not be identified in sediment samples. We share the new py GC/MS method to quantify highly crosslinked PUs in complex environmental matrices containing both inorganic and organic components. In the process of generating robust extraction methods for microplastics in sediment, we discovered important considerations for the quantitation of microplastics by py GC/MS and the impacts of sample matrix on the quantitation of PU and PP specifically. We provide guidance for the preparation of microplastics from complex environmental matrices (e.g., sediment and soil) for analysis by py GC/MS. Graphical Abstract
Developing Solid Particulate Vaccine Adjuvants: Surface Bound Antigen Favours a Humoural Response, whereas Entrapped Antigen Shows a Tendency for Cell Mediated Immunity (2013)

This present study compares the efficacy of microsphere formulations, and their method of antigen presentation, for the delivery of the TB sub-unit vaccine antigen, Ag85B-ESAT-6. Microspheres based on poly(lactide-coglycolide) (PLGA) and chitosan incorporating dimethyldioctadecylammonium bromide (DDA) were prepared by either the w/o/w double emulsion method (entrapped antigen) or the o/w single emulsion method (surface bound antigen), and characterised for their physico-chemical properties and their ability to promote an immune response to Ag85B-ESAT-6. The method of preparation, and hence method of antigen association, had a pronounced effect on the type of immune response achieved from the microsphere formulations, with surface bound antigen favouring a humoural response, whereas entrapped antigen favoured a cellular response.
Estimation of a time delay spread for wireless lan service environments (2003)

The wireless LAN service is becoming the hottest issue in these days. The reason is that any person can move freely and many computers can be connected to radio internet at the same time through a wireless LAN access point (AP)Consequently, the wireless LAN service is actively progressing, and being researched[1]. The wireless LAN service environment is mainly limited in indoors, unlike outdoor radio service of PCS. So, researches for the indoor propagation characteristics are being made lively. For high speed data transfer, wideband is required at the wireless LAN service. But in the indoor propagation characteristics, a time delay spread by multi-path due to the inter symbol interference (ISI) which takes place and degrades the whole system. Thus, researches on a time delay spread have been presented[2][3]. But the measurement analysis on various service environments has limits. So, in this work, model which can estimate a time delay spread through the 3D ray-tracing method is proposed and compared with the measurement results for various wireless LAN service environments.
Design and experiment of heuristic adaptive HVDC supplementary damping controller based on online Prony analysis (2007)

Adaptive damping controller is a challenging issue in the area of power system stability and control because of the difficulties in identification and design in real system. In this paper, a heuristic adaptive HVDC supplementary damping controller (AHDC) is designed based on online Prony analysis. Parameters of the controller are tuned according to the damping ratios of the weak-damped inter-area oscillation estimated by an improved Prony algorithm. The adaptive controller can achieve a desired damping effect without model-identification when the operating condition is changed. Numerical simulations of a real bulk power system and experimental results using real time digital simulator (RTDS) are presented to show its effectiveness. In the physical experiments, the adaptive controller is implemented by hardware, and phasor measurement unit (PMU) is also applied to acquire the selected feedback signal for a primary research of wide area damping control.
Effects of Pipeline Elevation Changes on Optimum Expelling Procedures for Gas Pipelines (2016)

Expeller performance has been evaluated in terms of the capability to create suction pressure at the throat. This formulation has been used to assess the effectiveness of evacuating combustible gases from an isolated, depressurized, pipeline section involving mainline block valves up to two times normal spacing with an intermediate vent stack. Additionally, the effects of elevation changes that promote buoyancy driven flows are accounted for in time as the interface between air and gas travels along the pipeline section during expelling. Two expelling strategies were introduced and assessed. These are simultaneous expelling, in which gas is expelled from the pipeline section from both ends, and sequential expelling, in which an intermediate vent stack is used to expel gas from the upstream and downstream segments. The effects of elevation changes and the location of the intermediate vent stack determine the best strategy for expelling so as to maximize the purge velocity in the section of a pipeline to be purged, while maintaining the mean flow velocity in the pipe above the minimum purge velocity to prevent air-gas stratification. It was found that for a ‘Flat-’ or a ‘Cusp-type’ elevation profile it is advantageous to follow a sequential expelling procedure using one expeller at the intermediate vent stack location. In the case of a ‘Vee-type’ elevation profile, a simultaneous expelling procedure is a better option in terms of expelling time, at the cost of needing to deploy two expellers to different sites quite far apart. Air ingress location depends on the expelling strategy and elevation profile.
Low cutoff G.657-compatible fibers for data center interconnects operating in the 1064 and 1310 nm windows (2020)

Optical interconnects in data centers have traditionally used 850 nm GaAs-based vertical-cavity surface-emitting lasers (VCSELs) in combination with multimode fiber, having a reach up to 100 m in length. Longer links typically use standard single-mode fiber in conjunction with either InP-based edge-emitting lasers or silicon photonic transmitters operating in the 1310 nm or 1550 nm window. Single-mode GaAs-based VCSELs operating at 1064 nm offer another path for achieving longer system reach. Potential advantages of these VCSELs include better power efficiency, modulation speeds reaching 50 Gbps and large-scale fabrication volumes. The longer wavelength is also beneficial due to the lower attenuation and chromatic dispersion of optical fibers at that wavelength. However, one practical issue for single-mode transmission is that the G.657 standard for single-mode fiber requires that the 22-meter cable cutoff wavelength be less than 1260 nm, and these fibers are typically few-moded at 1064 nm. The large differences between the group velocities of the LP01 and LP11 modes can lead to degradation of the system performance due to multi-path interference if the higher order modes are present. To resolve this quandary, we have designed and validated the performance of a new optical fiber which is single-moded at wavelengths less than 1064 nm, but also has G.657- compliant mode field diameter and dispersion characteristics that enable it to be used in the 1310 nm window.
The Importance of Salt-Enhanced Electrostatic Repulsion in Colloidal Crystal Engineering with DNA (2019)

Realizing functional colloidal single crystals requires precise control over nanoparticles in three dimensions across multiple size regimes. In this regard, colloidal crystallization with programmable atom equivalents (PAEs) composed of DNA-modified nanoparticles allows one to program in a sequence-specific manner crystal symmetry, lattice parameter, and, in certain cases, crystal habit. Here, we explore how salt and the electrostatic properties of DNA regulate the attachment kinetics between PAEs. Counterintuitively, simulations and theory show that at high salt concentrations (1 M NaCl), the energy barrier for crystal growth increases by over an order of magnitude compared to low concentration (0.3 M), resulting in a transition from interface-limited to diffusion-limited crystal growth at larger crystal sizes. Remarkably, at elevated salt concentrations, well-formed rhombic dodecahedron-shaped microcrystals up to 21 μm in size grow, whereas at low salt concentration, the crystal size typically does not exceed 2 μm. Simulations show an increased barrier to hybridization between complementary PAEs at elevated salt concentrations. Therefore, although one might intuitively conclude that higher salt concentration would lead to less electrostatic repulsion and faster PAE-to-PAE hybridization kinetics, the opposite is the case, especially at larger inter-PAE distances. These observations provide important insight into how solution ionic strength can be used to control the attachment kinetics of nanoparticles coated with charged polymeric materials in general and DNA in particular.
Predictive Inter-Radio Access Technology Handover (2012)

Inter-Radio Access Technology (IRAT) handovers are performed for dual mode devices when the quality of one radio access technology (RAT) falls below a threshold and the quality of another radio access technology is above a threshold.
Full Profiling of GE81112A, an Underexplored Tetrapeptide Antibiotic with Activity against Gram-Negative Pathogens (2023)

After the first total synthesis combined with structure revision, we performed thorough <i>in vitro</i> and <i>in vivo</i> profiling of the underexplored tetrapeptide GE81112A. From the determination of the biological activity spectrum and physicochemical and early absorption-distribution-metabolism-excretion-toxicity (eADMET) properties, as well as <i>in vivo</i> data regarding tolerability and pharmacokinetics (PK) in mice and efficacy in an Escherichia coli-induced septicemia model, we were able to identify the critical and limiting parameters of the original hit compound. Thus, the generated data will serve as the basis for further compound optimization programs and developability assessments to identify candidates for preclinical/clinical development derived from GE81112A as the lead structure. <b>IMPORTANCE</b> The spread of antimicrobial resistance (AMR) is becoming a more and more important global threat to human health. With regard to current medical needs, penetration into the site of infection represents the major challenge in the treatment of infections caused by Gram-positive bacteria. Considering infections associated with Gram-negative bacteria, resistance is a major issue. Obviously, novel scaffolds for the design of new antibacterials in this arena are urgently needed to overcome this crisis. Such a novel potential lead structure is represented by the GE81112 compounds, which inhibit protein synthesis by interacting with the small 30S ribosomal subunit using a binding site distinct from that of other known ribosome-targeting antibiotics. Therefore, the tetrapeptide antibiotic GE81112A was chosen for further exploration as a potential lead for the development of antibiotics with a new mode of action against Gram-negative bacteria.
The Effects of Absorption and Recombination on Quantum Dot Multijunction Solar Cell Efficiency (2013)

The key characteristics of quantum dot (QD)-enhanced multijunction solar cells (MJSC) are explored theoretically by focusing on the generation and recombination rates throughout the QD layers in the middle subcell. The quantum dots are modeled using an effective medium to describe light absorption, confinement, and recombination properties. We report an 8% increase in the short-circuit current density accompanied by a 3% drop in an open-circuit voltage for a QD- enhanced MJSC at 1 sun illumination (1 kW/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ) compared with a control MJSC without QD. The drop in an open-circuit voltage is due in part to the increased recombination rates in the depletion region, decreased carrier lifetimes in the QDs, and the increased recombination rates resulting from carrier escape and capture. Overall, these contribute to an absolute increase in efficiency of over 1% for the studied QD-enhanced MJSC design for a QD density of 125 QD/μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
Syntheses of Isoquinoline and Substituted Quinolines in Charged Microdroplets (2015)

A Pomeranz-Fritsch synthesis of isoquinoline and Friedländer and Combes syntheses of substituted quinolines were conducted in charged microdroplets produced by an electrospray process at ambient temperature and atmospheric pressure. In the bulk phase, all of these reactions are known to take a long time ranging from several minutes to a few days and to require very high acid concentrations. In sharp contrast, the present report provides clear evidence that all of these reactions occur on the millisecond timescale in the charged microdroplets without the addition of any external acid. Decreasing the droplet size and increasing the charge of the droplet both strongly contribute to reaction rate acceleration, suggesting that the reaction occurs in a confined environment on the charged surface of the droplet.
RFLP linkage map and genome analysis of Saccharum spontaneum (1993)

An RFLP linkage map of the wild sugarcane species Saccharum spontaneum L. (2n = 8x = 40-128) was constructed, comprising 216 loci, detected by 116 DNA probes, and distributed over 44 linkage groups. At a density of at least one marker every 25-cM interval, the coverage of the genome was estimated as 86%. For the generation of RFLP markers, probes were surveyed from seven DNA libraries: three sugarcane cDNA, one oat cDNA, one rice cDNA, and one barley cDNA, as well as one sugarcane genomic. Sixty-two maize genomic clones that were previously mapped on maize were used to initiate a comparative map between the sugarcane, sorghum, and maize genomes. Based on the RFLP segregation data, we conclude that this species is an autopolyploid, with an estimated genome size of 2107 cM.
Dual blockade of CXCL12‐CXCR4 and PD‐1–PD‐L1 pathways prolongs survival of ovarian tumor–bearing mice by prevention of immunosuppression in the tumor microenvironment (2019)

Blockade of immune-checkpoint programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 can enhance effector T-cell responses. However, the lack of response in many patients to checkpoint-inhibitor therapies emphasizes the need for combination immunotherapies to pursue maximal antitumor efficacy. We have previously demonstrated that antagonism of C-X-C chemokine receptor type 4 (CXCR4) by plerixafor (AMD3100) can decrease regulatory T (T<sub>reg</sub>)-cell intratumoral infiltration. Therefore, a combination of these 2 therapies might increase antitumor effects. Here, we evaluated the antitumor efficacy of AMD3100 and anti-PD-1 (αPD-1) antibody alone or in combination in an immunocompetent syngeneic mouse model of ovarian cancer. We found that AMD3100, a highly specific CXCR4 antagonist, directly down-regulated the expression of both C-X-C motif chemokine 12 (CXCL12) and CXCR4 <i>in vitro</i> and <i>in vivo</i> in tumor cells. AMD3100 and αPD-1 significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice when given as monotherapy. Combination of these 2 agents significantly enhanced antitumor effects compared with single-agent administration. Benefits of tumor control and animal survival were associated with immunomodulation mediated by these 2 agents, which were characterized by increased effector T-cell infiltration, increased effector T-cell function, and increased memory T cells in tumor microenvironment. Intratumoral T<sub>reg</sub> cells were decreased, and conversion of T<sub>reg</sub> cells into T helper cells was increased by AMD3100 treatment. Intratumoral myeloid-derived suppressor cells were decreased by the combined treatment, which was associated with decreased IL-10 and IL-6 in the ascites. Also, the combination therapy decreased suppressive leukocytes and facilitated M2-to-M1 macrophage polarization in the tumor. These results suggest that AMD3100 could be used to target the CXCR4-CXCL12 axis to inhibit tumor growth and prevent multifaceted immunosuppression alone or in combination with αPD-1 in ovarian cancer, which could be clinically relevant to patients with this disease.-Zeng, Y., Li, B., Liang, Y., Reeves, P. M., Qu, X., Ran, C., Liu, Q., Callahan, M. V., Sluder, A. E., Gelfand, J. A., Chen, H., Poznansky, M. C. Dual blockade of CXCL12-CXCR4 and PD-1-PD-L1 pathways prolongs survival of ovarian tumor-bearing mice by prevention of immunosuppression in the tumor microenvironment.
Transcriptional activation of Jun and Fos members of the AP‐1 complex is a conserved signature of immune aging that contributes to inflammaging (2023)

Diverse mouse strains have different health and life spans, mimicking the diversity among humans. To capture conserved aging signatures, we studied long-lived C57BL/6J and short-lived NZO/HILtJ mouse strains by profiling transcriptomes and epigenomes of immune cells from peripheral blood and the spleen from young and old mice. Transcriptional activation of the AP-1 transcription factor complex, particularly Fos, Junb, and Jun genes, was the most significant and conserved aging signature across tissues and strains. ATAC-seq data analyses showed that the chromatin around these genes was more accessible with age and there were significantly more binding sites for these TFs with age across all studied tissues, targeting pro-inflammatory molecules including Il6. Age-related increases in binding sites of JUN and FOS factors were also conserved in human peripheral blood ATAC-seq data. Single-cell RNA-seq data from the mouse aging cell atlas Tabula Muris Senis showed that the expression of these genes increased with age in B, T, NK cells, and macrophages, with macrophages from old mice expressing these molecules more abundantly than other cells. Functional data showed that upon myeloid cell activation via poly(I:C), the levels of JUN protein and its binding activity increased more significantly in spleen cells from old compared to young mice. In addition, upon activation, old cells produced more IL6 compared to young cells. In sum, we showed that the aging-related transcriptional activation of Jun and Fos family members in AP-1 complex is conserved across immune tissues and long- and short-living mouse strains, possibly contributing to increased inflammation with age.
Histological evidence supporting the durability of successful radiofrequency renal denervation in a normotensive porcine model (2022)

Reductions in renal NE, cortical axon density and downstream axonal loss caused by axonal destruction persisted through 180 days post-RDN in a normotensive swine model. These results suggest functional nerve regrowth after RF RDN is unlikely and support published clinical evidence that the procedure results in durable blood pressure reduction.
Parkinsonism mutations in DNAJC6 cause lipid defects and neurodegeneration that are rescued by Synj1 (2023)

Abstract Recent evidence links dysfunctional lipid metabolism to the pathogenesis of Parkinson’s disease, but the mechanisms are not resolved. Here, we generated a new Drosophila knock-in model of DNAJC6/Auxilin and find that the pathogenic mutation causes synaptic dysfunction, neurological defects and neurodegeneration, as well as specific lipid metabolism alterations. In these mutants, membrane lipids containing long-chain polyunsaturated fatty acids, including phosphatidylinositol lipid species that are key for synaptic vesicle recycling and organelle function, are reduced. Overexpression of another protein mutated in Parkinson’s disease, Synaptojanin-1, known to bind and metabolize specific phosphoinositides, rescues the DNAJC6/Auxilin lipid alterations, the neuronal function defects and neurodegeneration. Our work reveals a functional relation between two proteins mutated in Parkinsonism and implicates deregulated phosphoinositide metabolism in the maintenance of neuronal integrity and neuronal survival.