gebhart/patrepeval huggingface dataset:
Molecular mechanisms promoting progression of autoimmune myocarditis to dilated cardiomyopathy. (2017)

Abstract Myocarditis is an inflammatory disease of the myocardium, described by infiltration of immune cells and cardiomyocyte necrosis. It is a major cause of sudden death in young adults. Patients often progress to a more severe form of the disease termed dilated cardiomyopathy (DCM). It is characterized by extensive fibrosis leading to impaired cardiac function. Immunosuppressive treatments with corticosteroids (CSs) have not been effective in preventing the disease. We hypothesized that macrophage migration inhibitory factor (MIF), being the only known pro-inflammatory cytokine induced by CSs may play a role in resistance to CSs. Also, MIF counter-regulates CS-mediated immunosuppression. Using the experimental autoimmune myocarditis (EAM) animal model, we observed that MIF−/− mice treated with Dexamethasone (Dex) were highly resistant to EAM and progression to DCM. Furthermore, from a translational approach, treatment using small molecule inhibitors of MIF combined with Dex recapitulated this phenotype in wild type mice. We observed that treated mice showed decreased expression of key chemokines and extracellular matrix molecules compared with controls, implicating these molecules in disease progression. Currently, we are investigating these molecules by selectively inhibiting them in order to understand their contribution to disease pathogenesis. We observed that inhibition of CCL2 after, although not prior to establishment of EAM attenuated progression to DCM. Thereby, suggesting that CCL2 is predominantly involved during the fibrotic phase aiding in progression as opposed to the induction phase of the disease. Besides a novel approach to prevent DCM, our studies may provide new insights into the mechanisms driving DCM.
The Mechanism of Dedoping PEDOT:PSS by Aliphatic Polyamines (2019)

Poly(3,4-ethylenedioxythiophene) blended with polystyrenesulfonate and poly(styrenesulfonic acid), PEDOT:PSS, has found widespread use in organic electronics. Although PEDOT:PSS is commonly used in its doped electrically conducting state, the ability to efficiently convert PEDOT:PSS to its undoped nonconducting state is of interest for a wide variety of applications ranging from biosensors to organic neuromorphic devices. Exposure to aliphatic monoamines, acting as an electron donor and Brønsted-Lowry base, has been reported to be partly successful, but monoamines are unable to fully dedope PEDOT:PSS. Remarkably, some-but not all-polyamines can dedope PEDOT:PSS very efficiently to very low conductivity levels, but the exact chemical mechanism involved is not understood. Here, we study the dedoping efficacy of 21 different aliphatic amines. We identify the presence of two or more primary amines, which can participate in an intramolecular reaction, as the key structural motif that endows polyamines with high PEDOT:PSS dedoping strength. A multistep reaction mechanism, involving sequential electron transfer and deprotonation steps, is proposed that consistently explains the experimental results. Finally, we provide a simple method to convert the commonly used aqueous PEDOT:PSS dispersion into a precursor formulation that forms fully dedoped PEDOT:PSS films after spin coating and subsequent thermal annealing.
Drug resistance of oral bacteria to new antibacterial dental monomer dimethylaminohexadecyl methacrylate (2018)

Only two reports exist on drug-resistance of quaternary ammonium monomers against oral bacteria; both studies tested planktonic bacteria for 10 passages, and neither study tested biofilms or resins. The objectives of this study were to investigate the drug-resistance of Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii against dimethylaminohexadecyl methacrylate (DMAHDM), and to evaluate biofilms on resins with repeated exposures for 20 passages for the first time. DMAHDM, dimethylaminododecyl methacrylate (DMADDM) and chlorhexidine (CHX) were tested with planktonic bacteria. Biofilms were grown on a resin containing 3% DMAHDM. Minimum-inhibitory concentrations were measured. To detect drug-resistance, the survived bacteria from the previous passage were used as inoculum for the next passage for repeated exposures. S. gordonii developed drug-resistance against DMADDM and CHX, but not against DMAHDM. Biofilm colony-forming units (CFU) on DMAHDM-resin was reduced by 3-4 log; there was no difference from passages 1 to 20 (p > 0.1). No drug-resistance to DMAHDM was detected for all three bacterial species. In conclusion, this study showed that DMAHDM induced no drug-resistance, and DMAHDM-resin reduced biofilm CFU by 3-4 log, with no significant change from 1 to 20 passages. DMAHDM with potent antibacterial activities and no drug-resistance is promising for dental applications.
Effect of Low-viscosity Resin on the Micro-tensile Bond Strength of an 'All-in-one' Adhesive to Dentin (2000)

status: Published
Optimization of GaAs amplification photodetectors for 700% quantum efficiency (2003)

We investigate the device physics of novel GaAs waveguide photodetectors with integrated photon multiplication. Such detectors have the potential to achieve simultaneously high saturation power, high speed, high responsivity, and quantum efficiencies above 100%. Our device design vertically combines a bulk photodetector ridge waveguide region with laterally confined quantum wells for amplification. Measurements on the first device generation show quantum efficiencies of only 56%. Advanced device simulation is employed to analyze these devices and to reveal performance limitations. Excellent agreement between simulations and measurements is obtained. Device design optimization is proposed, promising more than 700% efficiency.
Quantitative Evaluation of CFTR Pre-mRNA Splicing Dependent on the (TG)mTn Poly-Variant Tract (2021)

Genetic analysis in cystic fibrosis (CF) is a difficult task. Within the many causes of variability and uncertainty, a major determinant is poor knowledge of the functional effect of most DNA variants of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. In turn, knowledge of the effect of a CFTR variant has dramatic diagnostic, prognostic and, in the era of CF precision medicine, also therapeutic consequences. One of the most challenging CFTR variants is the (TG)mTn haplotype, which has variable functional effect and controversial clinical consequences. The exact quantification of the anomalous splicing of CFTR exon 10 (in the HGVS name; exon 9 in the legacy name) and, consequently, of the residual wild-type functional CFTR mRNA, should be mandatory in clinical assessment of patients with potentially pathological haplotype of this tract. Here, we present a real time-based assay for the quantification of the proportion of exon 10+/exon 10- CFTR mRNA, starting from nasal brushing. Our assay proved rapid, economic and easy to perform. Specific primers used for this assay are either disclosed or commercially available, allowing any laboratory to easily perform it. A simplified analysis of the data is provided, facilitating the interpretation of the results. This method helps to enhance the comprehension of the genotype-phenotype relationship in CF and CFTR-related disorders (CFTR-RD), crucial for the diagnosis, prognosis and personalized therapy of CF.
Terahertz difference-frequency-generation quantum cascade lasers on silicon with wire grid current injectors (2022)

We propose the concept and experimentally verify the operation of terahertz quantum cascade laser sources based on intra-cavity Cherenkov difference-frequency generation on a silicon substrate with the current injection layer configured as a metal wire grid. Such a current injector configuration enables high transmission of TM-polarized terahertz radiation into the silicon substrate while simultaneously providing a low-resistivity metal contact for current injection.
Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging (2013)

X-ray fluoroscopy-guided endovascular procedures have several significant limitations, including difficult catheter navigation and use of ionizing radiation, which can potentially be overcome using a magnetically steerable catheter under MR guidance. The main goal of this work is to develop a microcatheter whose tip can be remotely controlled using the magnetic field of the MR scanner. This protocol aims to describe the procedures for applying current to the microcoil-tipped microcatheter to produce consistent and controllable deflections. A microcoil was fabricated using laser lathe lithography onto a polyimide-tipped endovascular catheter. In vitro testing was performed in a waterbath and vessel phantom under the guidance of a 1.5-T MR system using steady-state free precession (SSFP) sequencing. Various amounts of current were applied to the coils of the microcatheter to produce measureable tip deflections and navigate in vascular phantoms. The development of this device provides a platform for future testing and opportunity to revolutionize the endovascular interventional MRI environment.
Natural killer cells and malaria (2006)

Malaria, caused by the infection with parasites of the germs Plasmodium, is one of the three most important infectious diseases worldwide, along with tuberculosis and infection with human immunodeficiency virus. Natural killer (NK) cells are lymphocytes classically involved in the early defense against viral infections and intracytoplasmic bacterial infections and are also implicated during the course of tumor development and allogeneic transplantation. These cells display important cytotoxic activity and produce high levels of proinflammatory cytokines. In both mouse and human models of malaria, NK cells appear to be a major source of interferon-gamma during the early phase of infection. In humans, indirect signaling through monocytes/macrophages required to optimally stimulate NK cell activity. However, the in vivo functions of NK cells during malaria are still enigmatic, and many issues remain to be dissected, such as the molecular basis of the direct recognition of iRBCs by NK cells.
Low-complexity data-reuse RLS algorithm with increased robustness features (2023)

Recent advancements in the field of adaptive filters based on the least-squares minimization criterion propose a stable and efficient recursive least-squares (RLS) algorithm with attractive numerical properties and performance similar to the classical RLS methods. The combination between the RLS and the dichotomous coordinate descent (DCD) iterations (i.e., the RLS-DCD) offers an attractive option for practical applications with low requirements in terms of chip area. This paper employs a data-reuse methodology to further improve the tracking speed of the RLS-DCD algorithm. Furthermore, a regularization principle is used to develop its robustness features in low signal-to-noise working conditions.
Optical Frequency-Domain Reflectometry Based Distributed Temperature Sensing Using Rayleigh Backscattering Enhanced Fiber (2023)

An innovative optical frequency-domain reflectometry (OFDR)-based distributed temperature sensing method is proposed that utilizes a Rayleigh backscattering enhanced fiber (RBEF) as the sensing medium. The RBEF features randomly high backscattering points; the analysis of the fiber position shift of these points before and after the temperature change along the fiber is achieved using the sliding cross-correlation method. The fiber position and temperature variation can be accurately demodulated by calibrating the mathematical relationship between the high backscattering point position along the RBEF and the temperature variation. Experimental results reveal a linear relationship between temperature variation and the total position displacement of high backscattering points. The temperature sensing sensitivity coefficient is 7.814 μm/(m·°C), with an average relative error temperature measurement of -1.12% and positioning error as low as 0.02 m for the temperature-influenced fiber segment. In the proposed demodulation method, the spatial resolution of temperature sensing is determined by the distribution of high backscattering points. The temperature sensing resolution depends on the spatial resolution of the OFDR system and the length of the temperature-influenced fiber. With an OFDR system spatial resolution of 12.5 μm, the temperature sensing resolution reaches 0.418 °C per meter of RBEF under test.
A practical inverse-problem approach to digital holographic reconstruction (2013)

In this paper, we propose a new technique for high-quality reconstruction from single digital holographic acquisitions. The unknown complex object field is found as the solution of a nonlinear inverse problem that consists in the minimization of an energy functional. The latter includes total-variation (TV) regularization terms that constrain the spatial amplitude and phase distributions of the reconstructed data. The algorithm that we derive tolerates downsampling, which allows to acquire substantially fewer measurements for reconstruction compared to the state of the art. We demonstrate the effectiveness of our method through several experiments on simulated and real off-axis holograms.
Regenerative Principles Enrich Cardiac Rehabilitation Practice (2014)

Cardiovascular morbidity imposes a high degree of disability and mortality, with limited therapeutic options available in end-stage disease. Integral to standard of care, cardiac rehabilitation aims on improving quality-of-life and prolonging survival. The recent advent of regenerative technologies paves the way for a transformative era in rehabilitation medicine whereby, beyond controlling risk factors and disease progression, the prospect of curative solutions is increasingly tangible. To date, the spectrum of clinical experience in cardiac regenerative medicine relies on stem cell-based therapies delivered to the diseased myocardium either acutely/subacutely, after a coronary event, or in the setting of chronic heart failure. Application of autologous/allogeneic stem cell platforms has established safety and feasibility, with encouraging signals of efficacy. Newer protocols aim to purify cell populations in an attempt to eliminate nonregenerative and enrich for regenerative cell types before use. Most advanced technologies have been developed to isolate resident cell populations directly from the heart or, alternatively, condition cells from noncardiac sources to attain a disease-targeted lineage-specified phenotype for optimized outcome. Because a multiplicity of cell-based technologies has undergone phase I/II evaluation, pivotal trials are currently underway in larger patient populations. Translation of regenerative principles into clinical practice will increasingly involve rehabilitation providers across the continuum of patient care. Regenerative rehabilitation is thus an emerging multidisciplinary field, full of opportunities and ready to be explored.
Involvement of Ets Factor Spi-B, E Protein E2-2, and Id2 in Waldenstrom's Macroglobulinemia. (2009)

Abstract Abstract 2946 Poster Board II-922 Waldenström's macroglobulinemia (WM) is an incurable B cell disorder with a lymphoplasmacytic infiltrate in the bone marrow (BM) and IgM monoclonal gammopathy. WM tumor cells show variable differentiation, ranging from mature B-cells to plasma cells, which likely results from failure to fully undergo differentiation. In this study, we analyzed the expression of several genes involved in B cell differentiation by real time RT-PCR, such as Ets factors, the basic helix-loop-helix (bHLH) E proteins, as well as the inhibitors of DNA binding (Id) proteins which antagonize E protein activity. Comparison of BM CD19+ B cells obtained from 13 WM patients with 6 age-matched healthy donors showed that expression of the Ets factor Spi-B was increased four-fold, while Id2 was decreased three-fold. However, transcript levels of E proteins were similar between the two groups. Transduction of Spi-B in BCWM.1 WM cells resulted in two-fold higher levels of Id2 and five-fold lower levels of E2-2 compared with control. Id2 transduced BCWM.1 cells expressed two-fold lower levels of E2-2 and Spi-B. Taken together, these results implicate that increased expression of Spi-B alone cannot suppress Id2 transcription in the absence of E2-2 activity. Interestingly, overexpressing Spi-B while concomitantly knocking down Id2 increased the expression of the XBP-1 splicing isoform 2.5-fold without changing levels of Blimp-1 and IRF4. Moreover, inhibition of Spi-B expression by RNA interference or forced expression of Id2 in transduced BCWM.1 cells induced a significant decrease of anti-apoptotic Bcl-2. Importantly, we also showed that Spi-B co-immunoprecipated with Blimp-1 in nuclear extracts. Collectively, these data suggest that the regulatory network of the Spi-B, E2-2, and Id2 plays an essential role in B cell differentiation as well as the pathogenesis of WM, and suggests that Spi-B overexpression may block WM cell differentiation by sequestration of Blimp-1 while promoting tumor cell survival though up-regulation of Bcl-2. Disclosures: No relevant conflicts of interest to declare.
Abstract 3847: Inhibition of GCN2 sensitizes ASNS-downregulated cancer cells to asparaginase by disrupting amino acid response (2018)

Abstract General control nonderepressible 2 (GCN2) plays a major role in cellular response to amino acid limitation. Although maintenance of amino acid homeostasis is critical for tumor growth, little is known concerning the contribution of GCN2 to cancer cell proliferation and its potential as a therapeutic target. In this study, we demonstrate that inhibition of GCN2 with small-molecule compounds sensitizes cancer cells to anti-leukemic agent asparaginase (ASNase). We first tested acute lymphoblastic leukemia (ALL) cells and showed that treatment with GCN2 inhibitors rendered ALL cells sensitive to ASNase by preventing the induction of asparagine synthetase (ASNS). The prevention of ASNS expression suppresses asparagine synthesis and thus inhibits protein translation. In addition, comprehensive gene expression profiling revealed that the combined treatment induced stress-activated MAPK pathway and thereby triggering apoptosis. Using cell-panel analyses, we also identified a clear synergy between GCN2 inhibitors and ASNase in acute myelogenous leukaemia (AML) and pancreatic cancer cells besides ALL. Notably, basal ASNS expression levels were significantly correlated with sensitivity to combinatorial treatment. Furthermore, the combination displayed robust antitumor activity in mouse xenograft models of ALL, AML, and pancreatic cancer. These results demonstrate a novel mechanistic insight into a role of GCN2 in amino acid response and provide a rationale for further investigating GCN2 inhibitors for the treatment of cancer. Citation Format: Akito Nakamura, Tadahiro Nambu, Shunsuke Ebara, Yuka Hasegawa, Kosei Toyoshima, Yasuko Tsuchiya, Daisuke Tomita, Jun Fujimoto, Osamu Kurasawa, Chisato Takahara, Ayumi Kawamura, Ryuichi Nishigaki, Yoshinori Satomi, Akito Hata, Takahito Hara. Inhibition of GCN2 sensitizes ASNS-downregulated cancer cells to asparaginase by disrupting amino acid response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3847.
Quantitative Estimation of Beta Cell Sensitivity to Glucose in the Intact Organism: A Minimal Model of Insulin Kinetics in the Dog (1980)

We propose an approach to quantifying the sensitivity of B cells to glucose in the intact organism, whereby we interpret the complex dynamic plasma insulin response to glucose injection in terms of a minimal mathematical model of posthepatic insulin delivery and insulin clearance. The best model for this purpose was chosen by comparing the ability of a series of proposed models to account precisely for plasma insulin dynamics. Intravenous glucose tolerance tests (IVGTT) (300 mg/kg) were performed on conscious dogs, and blood was sampled frequently until the basal steady state was reestablished. Glucose injection produced variable plasma insulin responses, which were characterized by an early peak (76 microU/ml above basal), a plateau with occasional additional peaks, and by an abrupt return of plasma insulin to basal by 37 min. A set of eight models was examined; one emerged as superior, in that it was able to account for insulin dynamics with the smallest number of physiologically meaningful parameters (N = 4). The chosen (minimal) model assumes that (1) clearance of insulin is of the first order, (2) the initial peak represents a bolus of insulin loaded into the plasma after the glucose injection, and (3) the rate of the secondary rise in insulin is determined by the concentration of glucose in plasma above a specific threshold value. The sensitivity of first phase insulin delivery to glucose (phi 1; 1.28 +/- 0.15 microU/ml per min per mg/dl), the sensitivity of the secondary phase to glucose concentration [phi 2; 0.038 +/- 0.005 (microU/mg) . min-2], and the threshold for glucose stimulation of second phase secretion (h; 125 +/- 8 mg/100 ml) were all precisely estimated from the dynamic insulin responses. These three parameters of insulin kinetics (phi 1, phi 2, and h) can be calculated from a single IVGTT, and they characterize the insulin responsiveness of a single individual. Estimating these characteristic parameters of insulin kinetics from IVGTT data has potential for quantitating the individual factors contributing to glucose-stimulated insulin secretion in intact animal models, and it may be applicable to man.
Interaction of Localized Drivers and Disorganized Activation in Persistent Atrial Fibrillation (2018)

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02997254.
Bidirectional Current-Fed Half-Bridge (C) (LC)–(LC ) Configuration for Inductive Wireless Power Transfer System (2017)

This paper contributes to the analysis and development of a new power electronics system for bidirectional wireless power transfer (WPT). The major focus is the analysis and implementation of a new current-fed resonant topology with current-sharing and voltage-doubling features. A new bidirectional WPT system with current-fed half-bridge voltage-doubler circuit is proposed and analyzed with series-parallel and series resonant networks. Traditionally used parallel L-C resonant tank in transmitter circuit with current-fed WPT topology causes higher voltage stress across the inverter devices to compensate the reactive power consumed by the loosely coupled coil. In the proposed topology, this is mitigated by adding a suitably designed capacitor in series with the transmitter coil; thus, developing a series-parallel CLC tank. Detailed analysis and design is reported for both grid-to-vehicle and vehicle-to-grid operations. The power flow is controlled through variable frequency modulation. Soft switching of the devices is obtained irrespective of the load current. A proof-of-concept experimental hardware prototype rated at 1.2 kW is developed and tested. Experimental results are presented to verify the analysis and demonstrate the performance of the system with bidirectional power flow.