gebhart/patrepeval huggingface dataset:
Identification and In Vitro Expansion of Functional Antigen-Specific CD25 + FoxP3 + Regulatory T Cells in Hepatitis C Virus Infection (2008)

CD4(+)CD25(+) regulatory T cells (CD25(+) Tregs) play a key role in immune regulation. Since hepatitis C virus (HCV) persists with increased circulating CD4(+)CD25(+) T cells and virus-specific effector T-cell dysfunction, we asked if CD4(+)CD25(+) T cells in HCV-infected individuals are similar to natural Tregs in uninfected individuals and if they include HCV-specific Tregs using the specific Treg marker FoxP3 at the single-cell level. We report that HCV-infected patients display increased circulating FoxP3(+) Tregs that are phenotypically and functionally indistinguishable from FoxP3(+) Tregs in uninfected subjects. Furthermore, HCV-specific FoxP3(+) Tregs were detected in HCV-seropositive persons with antigen-specific expansion, major histocompatibility complex class II/peptide tetramer binding affinity, and preferential suppression of HCV-specific CD8 T cells. Transforming growth factor beta contributed to antigen-specific Treg expansion in vitro, suggesting that it may contribute to antigen-specific Treg expansion in vivo. Interestingly, FoxP3 expression was also detected in influenza virus-specific CD4 T cells. In conclusion, functionally active and virus-specific FoxP3(+) Tregs are induced in HCV infection, thus providing targeted immune regulation in vivo. Detection of FoxP3 expression in non-HCV-specific CD4 T cells suggests that immune regulation through antigen-specific Treg induction extends beyond HCV.
Supplementary Movie 1 from Involvement of the <i>RASSF1A</i> Tumor Suppressor Gene in Controlling Cell Migration (2023)

Supplementary Movie 1 from Involvement of the &lt;i&gt;RASSF1A&lt;/i&gt; Tumor Suppressor Gene in Controlling Cell Migration
Data from Combination of Two Insulin-Like Growth Factor-I Receptor Inhibitory Antibodies Targeting Distinct Epitopes Leads to an Enhanced Antitumor Response (2023)

&lt;div&gt;Abstract&lt;p&gt;The insulin-like growth factor-I receptor (IGF-IR) is a cell surface receptor tyrosine kinase that mediates cell survival signaling and supports tumor progression in multiple tumor types. We identified a spectrum of inhibitory IGF-IR antibodies with diverse binding epitopes and ligand-blocking properties. By binding distinct inhibitory epitopes, two of these antibodies, BIIB4 and BIIB5, block both IGF-I and IGF-II binding to IGF-IR using competitive and allosteric mechanisms, respectively. Here, we explored the inhibitory effects of combining BIIB4 and BIIB5. In biochemical assays, the combination of BIIB4 and BIIB5 improved both the potency and extent of IGF-I and IGF-II blockade compared with either antibody alone. In tumor cells, the combination of BIIB4 and BIIB5 accelerated IGF-IR downregulation and more efficiently inhibited IGF-IR activation as well as downstream signaling, particularly AKT phosphorylation. In several carcinoma cell lines, the antibody combination more effectively inhibited ligand-driven cell growth than either BIIB4 or BIIB5 alone. Notably, the enhanced tumor growth–inhibitory activity of the BIIB4 and BIIB5 combination was much more pronounced at high ligand concentrations, where the individual antibodies exhibited substantially reduced activity. Compared with single antibodies, the BIIB4 and BIIB5 combination also significantly further enhanced the antitumor activity of the epidermal growth factor receptor inhibitor erlotinib and the mTOR inhibitor rapamycin. Moreover, in osteosarcoma and hepatocellular carcinoma xenograft models, the BIIB4 and BIIB5 combination significantly reduced tumor growth to a greater degree than each single antibody. Taken together, our results suggest that targeting multiple distinct inhibitory epitopes on IGF-IR may be a more effective strategy of affecting the IGF-IR pathway in cancer. Mol Cancer Ther; 9(9); 2593–604. ©2010 AACR.&lt;/p&gt;&lt;/div&gt;
Backside Analysis: Focused-Ion-Beam Applications for Flip Chip Packaged ICs (2001)

Abstract Flip chip mounted devices are difficult debug using conventional FIB tools because their internal circuitry is not easily accessible. New flip chip focused ion beam (FC FIB) systems overcome this limitation, however, making it possible to access circuits from the backside through the bulk silicon. In this article, the authors explain how they used the new system to gain access to signal lines for backside waveform acquisition. They also describe some of the procedures they developed to repair and modify flip chip circuits from the backside and prepare cross-section samples from the backside for failure analysis and characterization.
A Linear GaN High Power Amplifier MMIC for <roman>Ka</roman>-Band Satellite Communications (2016)

A linear high power amplifier (HPA) monolithic microwave integrated circuit (MMIC) is designed with 0.15 μm gallium nitride (GaN) high electron mobility transistor (HEMT) technology on silicon carbide (SiC) substrate. To keep the linear characteristics of the power stage, 2:4:8 staging ratio of 8 × 50 μm unit transistor is adapted for the 3-stage HPA MMIC. The MMIC delivers P3 dB of 39.5 dBm with a PAE of 35% at 21.5 GHz. Linear output power (P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</sub> ) meeting IMD3 of -25 dBc is 37.3 dBm with an associated PAE of 29.5%. The MMIC dimensions are 3.4 mm × 2.5 mm, generating an output power density of 1049 mW/mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
The Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated Cytoskeletal Biomechanics (2018)

Exploration of human pulmonary artery endothelial cell (EC) as a prototypical biomechanical system has important pathophysiologic relevance because this cell type plays a key role in the development of a wide variety of clinical conditions. The complex hierarchical organization ranging from the molecular scale up to the cellular level has an intimate and intricate relationship to the barrier function between lung tissue and blood. To understand the innate molecule-cell-tissue relationship across varied length-scales, the functional role of c-Abl kinase in the cytoskeletal nano-biomechanics of ECs in response to barrier-altering agonists was investigated using atomic force microscopy. Concurrently, the spatially specific arrangement of cytoskeleton structure and dynamic distribution of critical proteins were examined using scanning electron microscopy and immunofluorescence. Reduction in c-Abl expression by siRNA attenuates both thrombin- and sphingosine 1-phosphate (S1P)-mediated structural changes in ECs, specifically spatially-defined changes in elastic modulus and distribution of critical proteins. These results indicate that c-Abl kinase is an important determinant of cortical actin-based cytoskeletal rearrangement. Our findings directly bridge the gap between kinase activity, structural complexity, and functional connectivity across varied length-scales, and suggest that manipulation of c-Abl kinase activity may be a potential target for the treatment of pulmonary barrier disorders.
Thermal Atomic Layer Deposition of Gold: Mechanistic Insights, Nucleation, and Epitaxy (2021)

An <i>in situ</i> microbalance and infrared spectroscopic study of alternating exposures to Me<sub>2</sub>Au(S<sub>2</sub>CNEt<sub>2</sub>) and ozone illuminates the organometallic chemistry that allows for the thermal atomic layer deposition (ALD) of gold. <i>In situ</i> quartz crystal microbalance (QCM) studies resolve the nucleation delay and island growth of Au on a freshly prepared aluminum oxide surface with single cycle resolution, revealing inhibition for 40 cycles prior to slow nucleation and film coalescence that extends over 300 cycles. <i>In situ</i> infrared spectroscopy informed by first-principles computation provides insight into the surface chemistry of the self-limiting half-reactions, which are consistent with an oxidized Au surface mechanism. X-ray diffraction of ALD-grown gold on silicon, silica, sapphire, and mica reveals consistent out-of-plane oriented crystalline film growth as well as epitaxially directed in-plane orientation on closely lattice-matched mica at a relatively low growth temperature of 180 °C. A more complete understanding of ALD gold nucleation, surface chemistry, and epitaxy will inform the next generation of low-temperature, nanoscale, textured depositions that are applicable to high surface area supports.
Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection (2021)

Abstract Background The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 114 million COVID-19 cases and &gt;2.5 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we investigated the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. Methods Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. Findings Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis. Interpretation Extreme older frail individuals and centenarians were able to elicit robust IgG and IgA antibodies directed toward SARS-CoV-2 spike protein. The antibodies were able to neutralize the virus. Humoral responses were still detectable after 60 days from initial diagnosis. Together, these data suggest that recovered participants who are of extreme old age would be protected if re-exposed to the same SARS-CoV-2 viral variant. Considering the threat of SARS-CoV-2 and COVID-19 to older age groups and long-term care facilities, the humoral responses to SARS-CoV-2 in older age groups is of public health importance and has implications to vaccine responses. Funding Canadian Institutes of Health Research (CIHR), NIH/NIAID, Genome Atlantic. VIDO receives operational funding from the Canada Foundation for Innovation through the Major Science Initiatives Fund and by Government of Saskatchewan through Innovation Saskatchewan.
Evaluating the use of pre-simulation in VLSI circuit partitioning (1994)

One of the significant difficulties in partitioning logic circuits for distributed simulation is the lack of a priori knowledge concerning the evaluation frequency of individual circuit elements. A number of researchers have resorted to pre-simulation to estimate these evaluation frequencies. In this paper we empirically investigate the wisdom of relying on pre-simulation results, and evaluate the degree to which early evaluation frequencies predict later evaluation frequencies. The results show that, for simulations that use random input vectors, pre-simulation has clear merit in predicting circuit element evaluation frequency. This supports the use of pre-simulation as an input to circuit partitioning algorithms.
Batch Virtual Adversarial Training for Graph Convolutional Networks (2019)

We present batch virtual adversarial training (BVAT), a novel regularization method for graph convolutional networks (GCNs). BVAT addresses the shortcoming of GCNs that do not consider the smoothness of the model's output distribution against local perturbations around the input. We propose two algorithms, sample-based BVAT and optimization-based BVAT, which are suitable to promote the smoothness of the model for graph-structured data by either finding virtual adversarial perturbations for a subset of nodes far from each other or generating virtual adversarial perturbations for all nodes with an optimization process. Extensive experiments on three citation network datasets Cora, Citeseer and Pubmed and a knowledge graph dataset Nell validate the effectiveness of the proposed method, which establishes state-of-the-art results in the semi-supervised node classification tasks.
Results from a phase 1 study of nusinersen (ISIS-SMN Rx ) in children with spinal muscular atrophy (2016)

Objective: To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMN Rx ), an antisense oligonucleotide designed to alter splicing of SMN2 mRNA, in patients with childhood spinal muscular atrophy (SMA).
Sensorless Temperature Estimation of Lithium-Ion Battery Based on Broadband Impedance Measurements (2022)

Temperature monitoring is of paramount importance for guaranteeing the safety and proper operation of lithium-ion batteries. Traditional temperature sensors suffer from heat transfer delay, where internal battery temperature cannot be measured directly. Motivated by this, this letter proposes a novel sensorless temperature estimation method based on broadband impedance spectroscopy. In this letter, pseudorandom sequence (PRS) with finite signal levels is utilized for impedance measurements. The measured impedance information is merged into an impedance-temperature model, which cooperates with a specially designed least-square method for temperature estimation. The proposed framework is robust against interference, whereas simple enough for online implementation. Experimental results suggest excellent estimation accuracy of the proposed method under different circumstances.
Design of Adaptive Pinhole SPECT Collimators for Improved Spatial Resolution and Sensitivity (2020)

We are designing AdaptiSPECT-C, a novel, multiple-detector, adaptive-aperture single-photon emission, tomographic (SPECT) system dedicated to brain imaging. This system is designed to change sensitivity and spatial resolution in realtime to address the needs of dynamic imaging[1]. The aim of this work is to document the creation of a manufacturable aperture design including hardware, electronics and software that effectively adapt in real-time spatial resolution and sensitivity functions to the needs of a dynamically changing subject. We accomplish these goals through metal printing of apertures and with custom control boards based on the Arduino microcontroller. With this design we are able to precisely control each aperture motion with a step resolution of 0.20 millimeters, which is within our required tolerances.
Mass Spectrometric Profiling of Intact Biological Tissue by Using Desorption Electrospray Ionization (2005)

Die direkte chemische Profilierung biologischer Gewebeproben, unter anderem von metastasenbildendem humanem Leberadenom, gelang durch Massenspektrometrie unter Standardbedingungen. Bei Desorptionselektrospray-Ionisierung zeigten sich intensivere Signale für Sphingolipide und stärker ungesättigte Phospholipide in der Tumorregion des Gewebes (siehe Bild).
Functional characterization of clinical isolates of the opportunistic fungal pathogen Aspergillus nidulans (2020)

Abstract Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency and virulence of A. nidulans isolates has mainly been studied in the context of the chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed biological characterization of two A. nidulans clinical isolates (CIs), obtained from a patient with breast carcinoma and pneumonia and from a patient with cystic fibrosis that underwent lung transplantation, and compared them to the reference, non-clinical A4 strain. Both CIs presented increased growth in comparison to the reference strain in the presence of physiologically-relevant carbon sources. Metabolomic analyses showed that the three strains are metabolically very different from each other in these carbon sources. Furthermore, the CIs were highly susceptible to cell wall perturbing agents but not to other physiologically-relevant stresses. Genome analyses identified several frame-shift variants in genes encoding cell wall integrity (CWI) signalling components. Significant differences in CWI signalling were confirmed by western blotting among the three strains. In vivo virulence studies using several different models revealed that strain MO80069 had significantly higher virulence in hosts with impaired neutrophil function when compared to the other strains. In summary, this study presents detailed biological characterization of two A. nidulans sensu stricto clinical isolates. Just like in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. Further studies are required to fully characterize A. nidulans strain-specific virulence traits and pathogenicity. Importance Immunocompromised patients are susceptible to infections with opportunistic filamentous fungi from the genus Aspergillus. Although A. fumigatus is the main etiological agent of Aspergillus spp.-related infections, other species, such as A. nidulans are prevalent in a condition-specific manner. A. nidulans is a predominant infective agent in patients suffering from chronic granulomatous disease (CGD). A. nidulans isolates have mainly been studied in the context of CGD, although infection with A. nidulans also occurs in non-CGD patients. This study carried out a detailed biological characterization of two non-CGD A. nidulans clinical isolates and compared it to a reference strain. Phenotypic, metabolomic and genomic analyses highlight fundamental differences in carbon source utilization, stress responses and maintenance of cell wall integrity among the strains. One clinical strain had increased virulence in models with impaired neutrophil function. Just as in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits.
Biosynthesis of type V procollagen by A204, a human rhabdomyosarcoma cell line. (1982)

The A204 cell line, derived from a human rhabdomyosarcoma, was studied in culture for its capacity to synthesize collagen types and other extracellular matrix proteins. The cells synthesized and secreted into the culture medium collagenous proteins with apparent molecular weights of 220,000 and 150,000. These were identified as the pro alpha 1 and pro alpha 2 chains of type V collagen by immunoprecipitation and by peptide mapping. The pro alpha 1(V) chain was made in excess of a 2:1 ratio for pro alpha 1(V) to pro alpha 2(V), and a fraction of the pro alpha 1(V) chains together with all of the pro alpha 2(V) chains participated in intermolecular disulfide bonding. The chains were extensively glycosylated at hydroxylysyl residues in ascorbate-supplemented cultures. A fraction of the secreted pro alpha 1(V) chains was processed to the p alpha 1(V) form, but further processing in the culture medium was very slow and the type V collagen molecules deposits in the extracellular matrix apparently retained large non-triple helical domains. Since the A204 cell line does not produce other collagen types, it may prove useful in further studies of the biosynthesis of type V procollagen.
On the Potential of MP-QUIC as Transport Layer Aggregator for Multiple Cellular Networks (2022)

Multipath transport protocols have the ability to simultaneously utilize the different paths and thus outperform single-path solutions in terms of achievable goodput, latency, or reliability. In this paper our goal is to examine the potential of connecting a mobile terminal to multiple mobile networks simultaneously in a dynamically changing environment. To achieve this, first we analyze a dataset obtained from an LTE drive test involving two operators. Then we study the performance of MP-QUIC, the multipath extension of QUIC, in a dynamic emulated environment generated from the collected traces. Our results show that MP-QUIC may leverage multiple available channels to provide uninterrupted connectivity, and a better overall goodput even when compared to using only the best available channel for communication. We also compare the MP-QUIC performance with MPTCP, identify challenges with the current protocol implementations to fill in the available aggregate capacity, and give insights on how the achievable throughput could be increased.
C-Terminal Provasopressin (Copeptin) as a Novel and Prognostic Marker in Acute Myocardial Infarction (2007)

The vasopressin system is activated after acute myocardial infarction. Copeptin may predict adverse outcome, especially in those with an elevated NTproBNP (more than approximately 900 pmol/L).
Modulation of macrophage differentiation and activation by decoy receptor 3 (2003)

Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily and is readily detected in certain cancer patients. Recently, we demonstrated that DcR3.Fc-treated dendritic cells skew T cell responses to a T helper cell type 2 phenotype. In this study, we further asked its ability to modulate CD14+ monocyte differentiation into macrophages induced by macrophage-colony stimulating factor in vitro. We found that DcR3.Fc was able to modulate the expression of several macrophage markers, including CD14, CD16, CD64, and human leukocyte antigen-DR. In contrast, the expression of CD11c, CD36, CD68, and CD206 (mannose receptor) was not affected in the in vitro culture system. Moreover, phagocytic activity toward immune complexes and apoptotic bodies as well as the production of free radicals and proinflammatory cytokines in response to lipopolysaccharide were impaired in DcR3.Fc-treated monocyte-derived macrophages. This suggests that DcR3.Fc might have potent, suppressive effects to down-regulate the host-immune system.
Interdependent Interactions between TFIIB, TATA Binding Protein, and DNA (2002)

Temperature-sensitive mutants of TFIIB that are defective for essential interactions were isolated. One mutation (G204D) results in disruption of a protein-protein contact between TFIIB and TATA binding protein (TBP), while the other (K272I) disrupts an interaction between TFIIB and DNA. The TBP gene was mutagenized, and alleles that suppress the slow-growth phenotypes of the TFIIB mutants were isolated. TFIIB with the G204D mutation [TFIIB(G204D)] was suppressed by hydrophobic substitutions at lysine 239 of TBP. These changes led to increased affinity between TBP and TFIIB. TFIIB(K272I) was weakly suppressed by TBP mutants in which K239 was changed to hydrophobic residues. However, this mutant TFIIB was strongly suppressed by conservative substitutions in the DNA binding surface of TBP. Biochemical characterization showed that these TBP mutants had increased affinity for a TATA element. The TBPs with increased affinity could not suppress TFIIB(G204D), leading us to propose a two-step model for the interaction between TFIIB and the TBP-DNA complex.