gebhart/patrepeval huggingface dataset:
P1‐228: Naturally occurring human antibodies to misfolded Aβ epitope associated with Alzheimer's disease (2012)

Immunotherapy has the potential for a safe and effective treatment of Alzheimer's disease (AD). The etiology of this disease is not yet clearly defined; however, research has implicated oligomers of the Aβ in AD pathology and specific epitopes in Aβ oligomers may be targeted by naturally occurring antibodies to play a role in clearing toxic Aβ oligomers and halting disease progression. The advantage of immunotherapy directed against an oligomer-specific epitope is the opportunity to directly target the pathogenic species and spare normal proteins, leading to greater efficacy and safety. Using a customized MagPlex TM immunoassay we screened 295 normal human plasma samples, ranging from 18 to 75 years of age, for the presence of antibodies to Aβ peptides; Aβ (1-40), Aβ (1-42), and proprietary SNK-cyclic peptide. Normal adult population exhibited antibodies to Aβ and percentage of high titers (MFI>50) to each Aβ epitope is shown (Figure 1). Results show that antibodies to the misfolded Aβ epitope SNK-cyclic peptide (50%) or Aβ(1-42) (66%) were detected in the majority of individuals. In contrast, the number with antibodies to Aβ (1-40) was very low (1-2%) and 15% of donors had no antibodies to any of the 3 Aβ peptides. Interestingly, when high titer individuals were assessed by age groups (Figure 2), there was a significant positive association between increasing age and levels of antibodies to Aβ (1-42) (Somers' d test, P <0.015). In contrast, there was a reverse trend for age and levels of antibodies to SNK-cyclic peptide. These results demonstrate a differential immune response to the various Aβ epitopes in a normal population that may provide a marker of AD progression and an association with age that merits further analysis. The screening study of AD patients will assess the distribution of antibodies in patients compared to a normal age-matched population. Proof-of-concept efficacy will use purified antibodies to the SNK-cyclic peptide to evaluate protection in vitro and in vivo. Graph depicting the percentage of donors with MFI>50 that had antibodies against each specific peptide. Graph depicting the percentage of donors (MFI>50) grouped by age decade that had antibodies against each specific peptide.
Broadband permittivity characterization of polymers up to 110GHz using co-planar waveguides (2021)

This work presents a method to characterize the complex permittivity of dielectric materials on top of co-planar waveguides (CPW). CPW lines made of aluminum are patterned on a 200mm quartz wafer and coated with a material under test (MUT). The S-parameters of the transmission lines are measured from 5GHz to 110GHz, and the propagation constant is calculated using the multiline TRL de-embedding technique. An analysis of the influence of the electrical properties of the MUT on the propagation constant shows that the attenuation constant depends on the complex permittivity, while the phase constant depends only on the relative permittivity. These relationships are exploited to extract the complex permittivity of the MUT with a 2D field solver by optimizing the MUT complex permittivity to match the measured propagation constant. For the purpose of this experiment, four materials are coated on separated wafers, and their complex permittivity values are extracted from 5GHz to 110GHz. Out of the four materials analyzed in this study, one exhibits a low dielectric constant of 2.5 and a loss tangent below 0.005 above 15GHz.
Realization of flexible AlGaN/GaN HEMT by laser liftoff (2022)

Abstract We demonstrate fully fabricated AlGaN/GaN high electron mobility transistors (HEMTs) transferred from sapphire to copper tape on flexible polyethylene terephthalate using 193 nm excimer laser liftoff (LLO). The heterojunction is structurally intact after LLO, leading to preserved electron mobility <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mrow> <mml:mi>μ</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>n</mml:mi> </mml:mrow> </mml:msub> </mml:math> ∼1630 cm 2 V −1 s −1 and carrier concentration <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" overflow="scroll"> <mml:msub> <mml:mrow> <mml:mi>n</mml:mi> </mml:mrow> <mml:mrow> <mml:mi>s</mml:mi> </mml:mrow> </mml:msub> </mml:math> ∼10 13 cm −2 . The maximum drain saturation current decreased by ∼18% after transfer, which is a lower reduction than other reported transfer methods. The drain current of this flexible HEMT increased monotonically under tensile stress applied using a convex-shaped plate, while the threshold voltage shifted more negative in quantitative agreement with the expected piezoelectric charge for an intact heterojunction.
Critical role for OX40 signaling in Thymic and Peripheral Treg Expansion (2017)

Abstract Regulatory T-cells (Treg) play a pivotal role in suppressing self-reactive effector T-cells (Teff) and help maintain the critical balance between self-tolerance and autoimmunity. Restoration of homeostatic balance between Teff/Treg cells has been shown to ameliorate many autoimmune diseases including type-1 diabetes. Recently, we have reported a novel strategy for the selective expansion of Tregs using OX40L (a TNF-superfamily ligand) and Jagged (JAG)-1 (a Notch family ligand) treatment independent of canonical TCR-signaling, but mediated through specific interaction between OX40L-OX40 and JAG1-Notch3 preferentially expressed on Tregs. OX40L-JAG1 treatment of NOD mice with soluble OX40L and JAG1 increased proliferation of peripheral Tregs and delayed the onset of diabetes. In the present study, we show that OX40L treatment significantly increased Tregs in the thymus by inducing proliferation of thymic Tregs independent of TCR-stimulation upon addition of exogenous IL-2. OX40−/− mice had reduced numbers of thymic Tregs compared to wild type (WT) controls. The reduction in thymic Treg numbers likely due to impaired ability of proliferation in response to OX40L. However, we did not observe any change in IL-2 sensitivity of thymocytes in OX40−/− mice. Mechanistic studies suggested that OX40L-IL-2 induced thymic Treg proliferation was mediated through NF-kB and AKT-mTOR-S6 signaling. Further, phenotypic characterization studies revealed a significant decrease in TIGIT+Treg population, often associated with Treg activation, in both thymus and spleen of OX40−/− mice compared to WT controls. Taken together, these results suggest a critical role for OX40L/OX40 signaling in the development as well as function of Tregs.
Design and Optimization Leading to an Orally Active TTK Protein Kinase Inhibitor with Robust Single Agent Efficacy (2019)

Triple negative breast cancer (TNBC) is an aggressive disease with high relapse rates and few treatment options. Outlined in previous publications, we identified a series of potent, dual TTK/CLK2 inhibitors with strong efficacy in TNBC xenograft models. Pharmacokinetic properties and kinome selectivity were optimized, resulting in the identification of a new series of potent, selective, and orally bioavailable TTK inhibitors. We describe here the structure-activity relationship of the 2,4-disubstituted-7 H-pyrrolo[2,3- d]pyrimidine series, leading to significant single agent efficacy in a TNBC xenograft model without body weight loss. The design effort evolving an iv-dosed TTK/CLK2 inhibitor to an orally bioavailable TTK inhibitor is described.
Energy-based adaptive focusing of waves: application to noninvasive aberration correction of ultrasonic wavefields (2009)

An aberration correction method based on the maximization of the wave intensity at the focus of an emitting array is presented. The potential of this new adaptive focusing technique is investigated for ultrasonic focusing in biological tissues. The acoustic intensity is maximized noninvasively through direct measurement or indirect estimation of the beam energy at the focus for a series of spatially coded emissions. For ultrasonic waves, the acoustic energy at the desired focus can be indirectly estimated from the local displacements induced in tissues by the ultrasonic radiation force of the beam. Based on the measurement of these displacements, this method allows determination of the precise estimation of the phase and amplitude aberrations, and consequently the correction of aberrations along the beam travel path. The proof of concept is first performed experimentally using a large therapeutic array with strong electronic phase aberrations (up to 2pi). Displacements induced by the ultrasonic radiation force at the desired focus are indirectly estimated using the time shift of backscattered echoes recorded on the array. The phase estimation is deduced accurately using a direct inversion algorithm which reduces the standard deviation of the phase distribution from sigma = 1.89 radian before correction to sigma = 0.53 radian following correction. The corrected beam focusing quality is verified using a needle hydrophone. The peak intensity obtained through the aberrator is found to be -7.69 dB below the reference intensity obtained without any aberration. Using the phase correction, a sharp focus is restored through the aberrator with a relative peak intensity of -0.89 dB. The technique is tested experimentally using a linear transmit/receive array through a real aberrating layer. The array is used to automatically correct its beam quality, as it both generates the radiation force with coded excitations and indirectly estimates the acoustic intensity at the focus with speckle tracking. This technique could have important implications in the field of high-intensity focused ultrasound even in complex configurations such as transcranial, transcostal, or deep seated organs.
“The Boy Who Cried Wolf” and Other Post-Trust Stories (2020)

The 2009 swine flu pandemic turned out to be milder than it seemed to be in the first few weeks, yet it was serious for those with serious illness or who were pregnant at the time. These features of the pandemic produced communications dilemmas for experts, including a threat to public trust. With reference to the moral tale of the “boy who cried wolf,” this chapter reflects on how people in our research spoke of the eventual mildness of the 2009 pandemic and how this situation was construed as a false alarm, with implications for public trust in science and politics surrounding world-scale problems such as pandemics, population vaccination, superbugs, and health security.
Electrochemical processes in electrospray ionization mass spectrometry (2000)

Editorial Comment Last month we presented, as a Special Feature, a set of five articles that constituted a Commentary on the fundamentals and mechanism of electrospray ionization (ESI). These articles produced some lively discussion among the authors on the role of electrochemistry in ESI. Six authors participated in a detailed exchange of views on this topic, the final results of which constitute this month's Special Feature. We particularly hope that younger scientists will find value in this month's Special Feature, not only for the science that it teaches but also what it reveals about the processes by which scientific conclusions are drawn. To a degree, the contributions part the curtains on these processes and show science in action. We sincerely thank the contributors to this discussion. The give and take of intellectual debate is not always easy, and to a remarkable extent this set of authors has maintained good humor and friendships, even when disagreeing strongly on substance. Graham Cooks and Richard Caprioli Copyright 2000 John Wiley & Sons, Ltd.
Aeroacoustic simulation of a cross-flow fan using lattice Boltzmann method with a RANS model (2021)

The present study developed an unsteady RANS approach based on the lattice Boltzmann method (LBM), which can perform direct aeroacoustic simulations of low-speed fans at lower computational cost compared with the conventional LBM-LES approach. In this method, the k-ω turbulence model is incorporated into the LBM flow solver, where the transport equations of k and ω are also computed by the lattice Boltzmann method, similar to the Navier-Stokes equations. In addition, moving boundaries such as fan rotors are considered by a direct-forcing immersed boundary method. This numerical method was validated in a two-dimensional simulation of a cross-flow fan. As a result, the simulation was able to capture an eccentric vortex structure in the rotor, and the pressure rise by the work of the rotor can be reproduced. Also, the peak sound of the blade passing frequency can be successfully predicted by the present method. Furthermore, the simulation results showed that the peak sound is generated by the interaction between the rotor blade and the flow around the tongue part of the casing.
Toll-like receptor 5 as a novel receptor for fungal zymosan (2021)

Microbial pathogens carry specific structural patterns which were termed pathogen-associated molecular patterns (PAMPs). Toll-like receptors (TLRs) as key elements for the recognition of microbial pathogens are necessary for the activation of innate immune pathways. TLRs are activated by binding PAMPs of bacteria, viruses and fungi and initiate a signaling pathway resulting in the activation of transcription factors which modulate the production of various proinflammatory cytokines. It is not fully clear in detail which microbial pattern is recognized by which TLR. Here we show for the first time that TLR5 is a strong receptor for the yeast particle zymosan. We have generated stable human cell lines with combinations of TLR2 and TLR5 knock in/knock out together with stable nuclear factor kappaB (NF-κB) luciferase reporters. We found that both receptors TLR5 and TLR2 lead to an independent activation of the NF-κB pathway when simulated with zymosan. Our results demonstrate that TLR5 is a receptor for the fungal particle zymosan in addition to bacterial fragments like flagellin. Distinct cytokine patterns might suggest that TLR5 is potentially important for the differentiation in the recognition of the specific type of the foreign microorganisms and in the specific host defense response.
Performance of an Adaptive Controller for the Neuromuscular Blockade Based on Inversion of a Wiener Model (2014)

Abstract An adaptive controller based on a minimally parameterized parsimonious Wiener model for the effect of the muscle relaxant rocuronium in the neuromuscular blockade is presented. The controller structure combines inversion of the recursively identified static nonlinearity of the Wiener model with a positive compartmental control law for the linearized system. The overall strategy exploits the fact that the model has only two parameters, which are estimated by an extended Kalman filter. Due to the fact that the positive control law for total mass conservation of compartmental systems is only proven to be convergent for time‐invariant systems, the identification of the parameter in the linear block of the minimally parameterized parsimonious Wiener model is stopped when the controller is turned on. The controller was implemented in the platform Galeno and tested in simulation and in thirteen real cases of patients under general anesthesia. The good reference tracking results and robustness to noise show the reliability of the proposed strategy.
A simplified sequence for observing deoxymyoglobin signals in vivo: Myoglobin excitation with dynamic unexcitation and saturation of water and fat (MEDUSA) (1997)

Abstract This paper describes a new, simplified pulse sequence for observing NMR signals from deoxymyoglobin in vivo. Paramagnetically shifted resonances from deoxymyoglobin can be exploited to noninvasively calculate intracellular oxygen tension in striated muscle. However, special sequences are required to observe these weak signals against the larger water and fat signals encountered in vivo. The pulse sequence described here, which is based on inversion recovery sequences, efficiently suppresses both water and fat resonances and can be implemented with short repetition rates. Moreover, it is perfectly suited for studies with surface coils, where RF inhomogeneities render other popular suppression sequences ineffective.
Performance of Quantized Equal Gain Transmission With Noisy Feedback Channels (2008)

In this paper, new results and insights are derived for the performance of multiple-input, single-output systems with beamforming at the transmitter, when the channel state information is quantized and sent to the transmitter over a noisy feedback channel. It is assumed that there exists a per-antenna power constraint at the transmitter, hence, the equal gain transmission (EGT) beamforming vector is quantized and sent from the receiver to the transmitter. The loss in received signal-to-noise ratio (SNR) relative to perfect beamforming is analytically characterized, and it is shown that at high rates, the overall distortion can be expressed as the sum of the quantization-induced distortion and the channel error-induced distortion, and that the asymptotic performance depends on the error-rate behavior of the noisy feedback channel as the number of codepoints gets large. The optimum density of codepoints (also known as the point density) that minimizes the overall distortion subject to a boundedness constraint is shown to be the same as the point density for a noiseless feedback channel, i.e., the uniform density. The binary symmetric channel with random index assignment is a special case of the analysis, and it is shown that as the number of quantized bits gets large the distortion approaches the same as that obtained with random beamforming. The accuracy of the theoretical expressions obtained are verified through Monte Carlo simulations.
Urinary bladder phantom mimicking mechanical properties and pressure during filling (2023)

<i>Objective.</i>Phantoms that mimic healthy or diseased organ properties can complement animal models for surgical planning, training, and medical device development. If urodynamic studies rely on pressure-volume curves to assess lower urinary tract symptoms, there is an unsatisfied need for a bladder phantom that accurately mimics the bladder stretching capabilities and compliant behaviour during physiological filling.<i>Approach.</i>We demonstrate the suitability of water-soluble 3D-printed moulds as a versatile method to fabricate accurate phantoms with anatomical structures reconstructed from medical images. We report a phantom fabricated with silicone rubber. A wire net limits the silicone expansion to model the cystometric capacity. A mathematical model describes the pressure increase due to passive hyperelastic properties.<i>Main results.</i>The phantom reproduces the bladder's mechanical properties during filling. The pressure-volume curve measured on the phantom is typical of cystometric studies, with a compliance of 25.2 ± 1mlcmH2O-1.The root-mean-square error between the theoretical model and experimental data is 2.7cmH2O.The compliance, bladder wall thickness, cystometric capacity and pressure near the cystometric capacity of the phantom can be tuned to mimic various pathologies or human variability.<i>Significance.</i>The manufacturing method is suitable for fabricating bladder and other soft and hollow organ phantoms. The mathematical model provides a method to determine design parameters to model healthy or diseased bladders. Soft hollow organ phantoms can be used to complement animal experimentations for developing and validating medical devices aiming to be anchored on these organs or monitor their activity through pressure and strain measurement.
Single Particle Measurement of Single Crystal LiCoO2 and Wire-Shaped LiCoO2 (2014)

Lithium-ion batteries (LIBs) with high gravimetric and volumetric energy density are very important key devices to encourage the popularization of an environmental friendly energy system, which is consisted of solar cells, wind power generations, smart grid, and batteries. LiCoO 2 is widely used as the active material for the positive electrode. Many researchers have reported the dynamics of crystal structure change accompanied with the lithium insertion and extraction 1 . In commercial Li-ion battery, the positive electrode is composite electrode which is composed of polycrystalline LiCoO 2 powder, binders and conductive agents. It is difficult to obtain the intrinsic property of LiCoO 2 from the composite electrode. LiCoO 2 thin film electrode is widely used as the model electrode in order to discuss the mechanism of charge and discharge reaction. However, the thin film electrode is not appropriate for commercial batteries. In this study, the single crystal LiCoO 2 powders and wire-shape LiCoO 2 particles which are accumulated one-dimensionally by single crystal LiCoO 2 are synthesized by a flux method in order to discuss the Li transfer phenomenon in LiCoO 2 crystal by using a single particle measurement technique. Figure 1 shows the SEM images of single crystal and wire-shaped LiCoO 2 . The single particle measurement technique is very powerful to measure the intrinsic electrochemical properties of the active material with 5~30 μm size, because it can eliminate the effect of binders and conductive agents. The schematic diagram of the single particle measurement system is demonstrated in Fig.2. This technique has revealed that LiCoO 2 , LiMn 2 O 4 and LiFePO 4 particles have very good rate characteristics 2-4 . This study focuses on the effect of morphological and crystalline variations of LiCoO 2 to the electrochemical characteristics. References 1) T. Ohzuku, and A. Ueda, J. Electrochem. Soc., 141 , 2972 (1994) 2) K. Dokko, N. Nakata, K. Kanamura, J. Power Sources 189 , 783 (2009) 3) T. Saito, H. Munakata, K. Kanamura, J. Soc. Inorg. Mater., Jpn., 18 , 201 (2011) 4) H. Munakata, B. Takemura, T. Saito, K. Kanamura, J. Power Sources 217 , 444 (2012)
Human osteosarcoma cells resistant to detachment by an Arg-Gly-Asp-containing peptide overproduce the fibronectin receptor. (1987)

MG-63 human osteosarcoma cells were selected for attachment and growth in the presence of increasing concentrations of a synthetic peptide containing the cell attachment-promoting Arg-Gly-Asp sequence derived from the cell-binding region of fibronectin. Cells capable of attachment and growth in 5-mM concentrations of a peptide having the sequence Gly-Arg-Gly-Asp-Ser-Pro overproduce the cell surface receptor for fibronectin. In contrast, these cells show no differences in the numbers of vitronectin receptor they express as compared with the parental MG-63 cells. In agreement with the resistance of the selected cells to detachment by the peptide, 25-fold more Arg-Gly-Asp-containing peptide is required to prevent the attachment of these cells to fibronectin-coated surfaces than is needed to inhibit the attachment of MG-63 cells to the same substrate. However, similar concentrations of this peptide inhibit attachment of both cell lines to vitronectin-coated surfaces. The increase in fibronectin receptor is due to an increase in the levels of mRNA encoding the fibronectin receptor. Because of the nature of the selection process, we reasoned that this increase might be due to amplification of the fibronectin receptor gene, but no increase in gene copy number was detected by Southern blot analysis. The peptide-resistant cells display a very different morphology from that of the MG-63 cells, one that has a greater resemblance to that of osteocytes. The resistant cells also grow much more slowly than the MG-63 cells. The increased fibronectin receptor and altered morphology and growth properties were stable for at least 3 mo in the absence of peptide. The enhanced expression of the fibronectin receptor on the resistant cells indicates that cells are capable of altering the amount of fibronectin receptor on their surface in response to environmental factors and that this may in turn affect the phenotypic properties of the cell.