gebhart/patrepeval huggingface dataset:
Inhibition of the Autophagy Pathway Synergistically Potentiates the Cytotoxic Activity of Givinostat (ITF2357) on Human Glioblastoma Cancer Stem Cells (2016)

Increasing evidence highlighted the role of cancer stem cells (CSCs) in the development of tumor resistance to therapy, particularly in glioblastoma (GBM). Therefore, the development of new therapies, specifically directed against GBM CSCs, constitutes an important research avenue. Considering the extended range of cancer-related pathways modulated by histone acetylation/deacetylation processes, we studied the anti-proliferative and pro-apoptotic efficacy of givinostat (GVS), a pan-histone deacetylase inhibitor, on cell cultures enriched in CSCs, isolated from nine human GBMs. We report that GVS induced a significant reduction of viability and self-renewal ability in all GBM CSC cultures; conversely, GVS exposure did not cause a significant cytotoxic activity toward differentiated GBM cells and normal mesenchymal human stem cells. Analyzing the cellular and molecular mechanisms involved, we demonstrated that GVS affected CSC viability through the activation of programmed cell death pathways. In particular, a marked stimulation of macroautophagy was observed after GVS treatment. To understand the functional link between GVS treatment and autophagy activation, different genetic and pharmacological interfering strategies were used. We show that the up-regulation of the autophagy process, obtained by deprivation of growth factors, induced a reduction of CSC sensitivity to GVS, while the pharmacological inhibition of the autophagy pathway and the silencing of the key autophagy gene <i>ATG7</i>, increased the cell death rate induced by GVS. Altogether these findings suggest that autophagy represents a pro-survival mechanism activated by GBM CSCs to counteract the efficacy of the anti-proliferative activity of GVS. In conclusion, we demonstrate that GVS is a novel pharmacological tool able to target GBM CSC viability and its efficacy can be enhanced by autophagy inhibitory strategies.
Fifth-order Aberration Coefficients for Plane-symmetric Optical Systems (2021)

We present the analytical form of the fifth-order aberration coefficients for plane-symmetric optical systems expressed as a function of first-order system parameters and the paraxial chief and marginal ray angles and heights.
Fluoride release and recharge behavior of a nano-filled resin-modified glass ionomer compared with that of other fluoride releasing materials. (2011)

The cumulative amount of fluoride released from KN, VT and FLC and the release profiles were statistically similar but greater than that for FIX at P < 0.05. All four materials, including KN, showed a burst of fluoride ions at shorter times (t) and an overall rate dependence on t1/2 typical for glass-ionomers. The coating of KN with its primer and of DY with its adhesive did not significantly alter the fluoride release behavior of the respective materials. The overall rate for KN was significantly higher than for the compomer DY. DY showed a linear rate of release vs. t and no burst effect as expected for compomers. The nanoionomer KN showed fluoride recharge behavior similar to the conventional glass ionomers FIX and KM. Thus, it was concluded that the new RMGI KN exhibits fluoride ion release behavior similar to typical conventional and RMGIs and that the primer does not impede the release of fluoride.
Author response: A common mechanism underlies changes of mind about decisions and confidence (2015)

To understand how the brain makes decisions is to understand how we think – how we deal with information, interpret it and agree with a particular interpretation of the information. Neuroscience has begun to uncover the mechanisms that underlie these processes by linking the activity of nerve cells in the brain to different aspects of making decisions. These include how long it takes to reach a decision, why we make errors and how confident we feel about a decision. Sometimes when we make a decision and have committed to an answer, we then change our minds. Now, van den Berg et al. have asked whether the brain mechanisms that support a change of mind also support a change in confidence. To investigate this problem, human volunteers were asked to perform a difficult task where they had to decide whether a field of randomly moving dots had a tendency to drift to the left or to the right. During the experiment, van den Berg et al. recorded how long the volunteers took to make their decision, how confident the volunteers felt about their choice, and whether they were correct. Analyzing this data revealed that all of these measures could be explained by a mechanism where the brain accumulates evidence only until there appears to be enough evidence to favor one choice over the other. This process specifies how confident an individual should be based on the quality of the sensory evidence and how long it takes to make a decision. In addition, van den Berg et al. found that occasionally a volunteer changed their mind about how confident they were about a decision after they’d made it, as if they had continued to think about it. This was despite the volunteers receiving no more information about the task or how well they had done once they had made their decision. Therefore, it appears that the brain processed additional information that had already been detected but did not have time to affect the initial choice. The activity of the nerve cells in the brain was not recorded as the volunteers made their decisions. Future experiments that incorporate these measurements could help reveal how the brain performs the necessary computations and account for the time delay seen in processing some of the data. Where is this delayed information processed in the brain, and how does it lead to a change of mind?
Role of endogenous peptide in human alloreactive cytotoxic T cell responses (1992)

The T x B hybrid 174 x CEM.T2 (T2) has been shown to be defective in the processing of proteins for presentation by MHC class I molecules. It continues, however, to express significant quantities of HLA-A2.1, suggesting that this class I molecule is expressed either in a largely peptide-free form or in association with a small subset of peptides. In this paper T2 was used in conjunction with limiting dilution analysis to provide a direct estimate of the fraction of alloreactive cytotoxic T lymphocytes (CTLs) that were dependent upon the presence of peptides for their recognition of HLA-A2.1. Alloreactive cytotoxic T cell lines generated by stimulation with HLA-A2.1 expressing peripheral blood lymphocytes recognized T2 poorly. Split-well analysis of 240 clonal limiting dilution cultures demonstrated that this reflected the existence of two subpopulations. An average 85% of HLA-A2.1 specific CTLs recognized HLA-A2.1 on normal cells but not on T2. The remainder recognized HLA-A2.1 on both T2 and normal targets. CTL lines with the latter specificity could be generated by using T2 as a stimulator cell. Using target cells that either expressed a lower density of HLA-A2.1 or that expressed HLA-A2 molecules that had been mutated to affect CD8 binding, no significant differences in avidity between T2-reactive and T2-unreactive CTLs were seen. Thus the failure of the majority of alloreactive CTLs to recognize T2 is not a consequence of the lower level of HLA-A2.1 surface expression on this cell, but is instead due to the absence of appropriate epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)
Waveform Optimization for Wireless Power Transfer with Power Amplifier and Energy Harvester Non-linearities (2022)

Waveform optimization has recently been shown to be a key technique to boost the efficiency and range of far-field wireless power transfer (WPT). Current research has optimized transmit waveform adaptive to channel state information (CSI) and accounting for energy harvester (EH)’s non-linearity but under the assumption of linear high power amplifiers (HPA) at the transmitter. This paper proposes a channel-adaptive waveform design strategy that optimizes the transmitter’s input waveform considering both HPA and EH non-linearities. Simulations demonstrate that HPA’s non-linearity degrades the energy harvesting efficiency of WPT significantly, while the performance loss can be compensated by using the proposed optimal input waveform.
Quantification of Carrier Density Gradients along Axially Doped Silicon Nanowires Using Infrared Nanoscopy (2019)

Doped semiconductor nanostructures are interesting for the fabrication of nanoscale electronic and photonic devices. Here, we use scattering-type scanning near-field optical microscopy (s-SNOM) to characterize axial carrier density gradients in phosphorus-doped silicon nanowires. We quantitatively determine the carrier density and length of the doped segment as well as the functional form of the charge carrier gradient in the transition region between doped and nominally undoped segments. These measurements are enabled by understanding and accounting for the influence of the native oxide on the near-field optical contrasts in the transition region. Our results are supported by correlative energy dispersive X-ray spectroscopy (EDS) measurements. This work demonstrates the ability of s-SNOM to directly probe nanoscale charge carrier density transitions through thin surface layers, a capability that is important for a variety of doped semiconductor systems.
New La-Ti-O perovskite oxide thin films for miniaturized notch antenna (2013)

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Phrenic, but not hypoglossal, motor output is diminished in a rat model of amyotrophic lateral sclerosis (ALS) (2006)

ALS causes motoneuron degeneration and, ultimately, patient death by respiratory failure. We investigated the capacity to maintain respiratory motor output in a transgenic rat model of ALS that over expresses a mutated form of superoxide dismutase-1 (SOD1G93A). Phrenic and hypoglossal nerve output were recorded from anesthetized, vagotomized and ventilated end-stage SOD1G93A or wild type rats at different levels of respiratory drive regulated by controlling arterial PCO2 levels between the apneic CO2-threshold (SOD1G93A: 41±1 mmHg; wild type: 42±2 mmHg) and severe hypercapnia (90 mmHg). During baseline conditions (3 mmHg above CO2-threshold), phrenic burst amplitude was significantly less in SOD1G93A (1.2±0.2 Volts) vs wild type rats (2.8±0.4 V; p < 0.01), a relationship that persisted during hypercapnia (SOD1G93A: 2.4±0.5 V; wild type: 4.6±0.4 V; p < 0.01). Immunohistochemistry showed decreased motoneuron cell counts in the phrenic motor nucleus. In contrast, XII activity was similar in SOD1G93A and wild type rats in all conditions studied, and XII motoneuron cell counts were normal relative to wild type rats. As ventilation is normal or enhanced during hypercapnia in unanesthetized SOD1G93A rats, compensatory mechanisms preserve the capacity to breathe until late stage disease. Whereas ventilation in intact rats may not be a reliable quantitative index of respiratory compromise in this animal model, phrenic nerve recordings demonstrate clear functional impairment and may be a useful indicator of disease progression. Supported by ALS Association and NIH HL 89209, HL 65383 and HL07654.
Optimal joint azimuth-elevation and signal-array response estimation using parallel factor analysis (2002)

We consider deterministic joint azimuth-elevation, signal, and array response estimation, and establish a direct link to parallel factor (PARAFAC) analysis, a tool with roots in linear algebra for multi-way arrays. This link affords a powerful identifiability result, plus the opportunity to tap on and extend the available expertise for fitting the PARAFAC model, to derive a deterministic (least squares) joint estimation algorithm, also applicable to multiple-parameter/multiple-invariance ESPRIT subspace fitting problems. These and other issues are demonstrated in pertinent simulation experiments.
Framework for Analysis of Recurring Freeway Bottlenecks (2008)

Recent statistics indicate a dramatic increase in congestion delay due to recurrent freeway bottlenecks. Proper identification of freeway bottlenecks and their causes is the key to formulating plans for reducing congestion. Relatively low-cost geometric and operational improvements can often mitigate the effects of a bottleneck. The paper presents the findings to-date on an ongoing NCHRP project on low cost improvements for recurring freeway bottlenecks. The research surveyed the state of the art and practice both in the US and overseas, proposed a definition of bottlenecks, bottleneck classification and mitigation measures, and developed a framework for analysis of freeway bottlenecks that can be applied using both real-time and historical data. A bottleneck identification algorithm was also implemented in an archival system of surveillance data. The end product of this research will be a technical guide with step-by-step application analysis of the bottleneck impacts, both local and system-wide, and determination and assessment of mitigation measures.
Multilevel Lithographic Fabrication (2015)

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Workpiece Positioning Analyses: The Exact Solutions and a Quadratic Variation Approximation Using the Method of Moments (2008)

This paper presents algorithms for workpiece positioning analysis under locating errors. Workpiece constraint equations are first constructed using the method of homogenous coordinate transformation. These constraint equations are solved numerically for exact workpiece positional deviations by means of deterministic analysis (using the Newton–Raphson method) and variation analysis (i.e., random analysis using a Monte Carlo simulation). To enhance numerical efficiency in variation analysis, we further propose a quadratic approximation solution using the method of moments instead of the Monte Carlo method. Several case studies are presented to exemplify the proposed algorithms, with comparisons to prior literature results on linear and quadratic analyses. The criterion for using the proposed quadratic variation analysis versus the linear method and Monte Carlo simulation is also presented. By using the proposed algorithms, the exact workpiece positioning errors or quadratic variation approximations can be calculated, with consideration of workpiece surface nonlinearity, interactions between locating errors, and the impact of noninfinitesimal locating errors. This paper represents algorithmic advancement in the field where exact solutions and approximations can all be obtained at users’ choice.
Iterative tuning of feedforward controller with force ripple compensation for wafer stage (2008)

Iterative controller tuning is a method to fine-tune controllers in a repetitive process using only data collected in experiment runs. The controller parameters are chosen so as to minimize a certain cost function. The values of the parameters are updated iteratively based on tracking error in a gradient search. Iterative controller tuning is an advantageous method of controller tuning because no prior plant model is necessary. In this paper, we iteratively tune the feedforward controller of a wafer stage of a photolithography machine. A fixed-structure feedforward controller consisting of the inverted plant model was tuned. In addition, an additive feedforward term for compensation of nonlinear force ripple disturbance was tuned. The feedforward controller is tuned with the objective of minimizing a cost function that is a quadratic function of tracking error. Simulation and experimental results are presented which show that the iterative tuning method effectively reduced tracking error.
Photonic crystal enhanced fluorescence for early breast cancer biomarker detection (2012)

Photonic crystal surfaces offer a compelling platform for improving the sensitivity of surface-based fluorescent assays used in disease diagnostics. Through the complementary processes of photonic crystal enhanced excitation and enhanced extraction, a periodic dielectric-based nanostructured surface can simultaneously increase the electric field intensity experienced by surface-bound fluorophores and increase the collection efficiency of emitted fluorescent photons. Through the ability to inexpensively fabricate photonic crystal surfaces over substantial surface areas, they are amenable to single-use applications in biological sensing, such as disease biomarker detection in serum. In this review, we will describe the motivation for implementing high-sensitivity, multiplexed biomarker detection in the context of breast cancer diagnosis. We will summarize recent efforts to improve the detection limits of such assays though the use of photonic crystal surfaces. Reduction of detection limits is driven by low autofluorescent substrates for photonic crystal fabrication, and detection instruments that take advantage of their unique features.
Zinc, Copper and Oxalocalcic Urolithiasis (1993)

The possible effects of Zn and Cu in oxalocalcic urolithiasis were investigated. The formation of calcium oxalate crystals in the presence of Zn and Cu demonstrated that their morphology is clearly affected by these ions. Thus, when such ions were present in a number of higher concentrations, a notable increase in the primary aggregation was clearly detected. On the other hand, Zn and Cu urinary levels were determined in groups of stone-formers and healthy people. Zinc urinary concentration was significantly lower for lithiasic than for healthy people and the copper urinary concentration was lower for lithiasic than healthy males, but both female groups had a similar copper urinary concentration. The mentioned differences disappeared when serum levels were considered. These obtained results have been comparatively evaluated with those obtained by other authors. When considering all the commented aspects, it is concluded that no important direct action of zinc and copper on oxalocalcic calculi genesis takes place.
Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Ulcerative Colitis (2019)

In a randomized trial of patients with UC, mirikizumab was effective in inducing a clinical response after 12 weeks. Additional studies are required to determine the optimal dose for induction of remission. Mirikizumab showed durable efficacy throughout the maintenance period. Clinicaltrials.gov, Number NCT02589665.
Investigation of AlGaN/GaN high electron mobility transistor structures on 200-mm silicon (111) substrates employing different buffer layer configurations (2016)

AlGaN/GaN high electron mobility transistor (HEMT) structures are grown on 200-mm diameter Si(111) substrates by using three different buffer layer configurations: (a) Thick-GaN/3 × {Al<sub>x</sub>Ga<sub>1-x</sub>N}/AlN, (b) Thin-GaN/3 × {Al<sub>x</sub>Ga<sub>1-x</sub>N}/AlN, and (c) Thin-GaN/AlN, so as to have crack-free and low-bow (<50 μm) wafer. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, high resolution-cross section transmission electron microscopy, optical microscopy, atomic-force microscopy, cathodoluminescence, Raman spectroscopy, X-ray diffraction (ω/2θ scan and symmetric/asymmetric ω scan (rocking curve scan), reciprocal space mapping) and Hall effect measurements are employed to study the structural, optical, and electrical properties of these AlGaN/GaN HEMT structures. The effects of buffer layer stacks (i.e. thickness and content) on defectivity, stress, and two-dimensional electron gas (2DEG) mobility and 2DEG concentration are reported. It is shown that 2DEG characteristics are heavily affected by the employed buffer layers between AlGaN/GaN HEMT structures and Si(111) substrates. Particularly, we report that in-plane stress in the GaN layer affects the 2DEG mobility and 2DEG carrier concentration significantly. Buffer layer engineering is shown to be essential for achieving high 2DEG mobility (>1800 cm<sup>2</sup>/V∙s) and 2DEG carrier concentration (>1.0 × 10<sup>13</sup> cm<sup>-2</sup>) on Si(111) substrates.
A Rationally Designed Humanized Antibody Selective for Amyloid Beta Oligomers in Alzheimer’s Disease (2019)

Advances in the understanding of Alzheimer's disease (AD) suggest that pathogenesis is not directly related to plaque burden, but rather to soluble toxic amyloid-beta oligomers (AßO). Therapeutic antibodies targeting Aß monomers and/or plaque have shown limited efficacy and dose-limiting adverse events in clinical trials. These findings suggest that antibodies capable of selectively neutralizing toxic AßO may achieve improved efficacy and safety. To this end, we generated monoclonal antibodies against a conformational Aß epitope predicted by computational modeling to be presented on toxic AßO but not monomers or fibrils. The resulting lead antibody, PMN310, showed the desired AßO-selective binding profile. In vitro, PMN310 inhibited AßO propagation and toxicity. In vivo, PMN310 prevented AßO-induced loss of memory formation and reduced synaptic loss and inflammation. A humanized version (huPMN310) compared favorably to other Aß-directed antibodies showing a lack of adverse event-associated binding to Aß deposits in AD brains, and greater selective binding to AßO-enriched AD brain fractions that contain synaptotoxic Aß species. Systemic administration of huPMN310 in mice resulted in brain exposure and kinetics comparable to those of other therapeutic human monoclonal antibodies. Greater selectivity for AßO and the potential to safely administer high doses of huPMN310 are expected to result in enhanced safety and therapeutic potency.
Three-dimensional real-time imaging of cardiac cell motions in living embryos (2008)

While quantitative analysis of dynamic biological cell motions in vivo is of great biomedical interest, acquiring 3-D (plus time) information is difficult due to the lack of imaging tools with sufficient spatial and temporal resolution. A novel 3-D high-speed microscopic imaging system is developed to enable 3-D time series data acquisition, based on a defocusing technique (DDPIV). Depth coordinate Z is resolved by the triangular image patterns generated by a mask with three apertures forming an equilateral triangle. Application of this technique to microscale imaging is validated by calibration of targets spread over the image field. 1-microm fluorescent tracer particles are injected into the blood stream of 32 h post-fertilization developing zebrafish embryos to help describe cardiac cell motions. 3-D and velocity fields of cardiovascular blood flow and trajectories of heart-wall motions are obtained.
Multiwavelength modelocked semiconductor lasers for photonic access network applications (2007)

High performance, inexpensive light sources are needed for the advancement of wavelength division multiplexed (WDM) photonic access networks. In this paper, the unique features of multiwavelength modelocked semiconductor lasers are demonstrated with an emphasis on possible integration into access networks. An evaluation of multiwavelength passive, active, and hybrid modelocking reveals that hybrid modelocking is optimum for the suppression of mode partition noise as well as coherence tailoring in multiwavelength lasers. Low-distortion propagation of 10 channeltimes5 GHz multiwavelength pulses through multimode fiber is achieved. Intracavity gain flattening enables the simultaneous generation of 6 GHz pulse trains into 168 parallel wavelength channels for a 1 THz aggregate pulse rate from a single laser source. This work conveys the potential for semiconductor laser modelocking to produce multiple telecommunications wavelengths for data transmission and auxiliary functions in photonic networking