gebhart/patrepeval huggingface dataset:
FOXO3 Modulates Endothelial Gene Expression and Function by Classical and Alternative Mechanisms (2010)

FOXO transcription factors represent targets of the phosphatidylinositol 3-kinase/protein kinase B survival pathway controlling important biological processes, such as cell cycle progression, apoptosis, vascular remodeling, stress responses, and metabolism. Recent studies suggested the existence of alternative mechanisms of FOXO-dependent gene expression beyond classical binding to a FOXO-responsive DNA-binding element (FRE). Here we analyzed the relative contribution of those mechanisms to vascular function by comparing the transcriptional and cellular responses to conditional activation of FOXO3 and a corresponding FRE-binding mutant in human primary endothelial cells. We demonstrate that FOXO3 controls expression of vascular remodeling genes in an FRE-dependent manner. In contrast, FOXO3-induced cell cycle arrest and apoptosis occurs independently of FRE binding, albeit FRE-dependent gene expression augments the proapoptotic response. These findings are supported by bioinformatical analysis, which revealed a statistical overrepresentation of cell cycle regulators and apoptosis-related genes in the group of co-regulated genes. Molecular analysis of FOXO3-induced endothelial apoptosis excluded modulators of the extrinsic death receptor pathway and demonstrated important roles for the BCL-2 family members BIM and NOXA in this process. Although NOXA essentially contributed to FRE-dependent apoptosis, BIM was effectively induced in the absence of FRE-binding, and small interfering RNA-mediated BIM depletion could rescue apoptosis induced by both FOXO3 mutants. These data suggest BIM as a critical cell type-specific mediator of FOXO3-induced endothelial apoptosis, whereas NOXA functions as an amplifying factor. Our study provides the first comprehensive analysis of alternatively regulated FOXO3 targets in relevant primary cells and underscores the importance of such genes for endothelial function and integrity.
Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination (2018)

Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing radiation therapy (RT) has been shown to enhance the priming and effector phases of the antitumor T-cell response rendering it an attractive therapy to combine with PD-1/PD-L1 inhibitors. Preclinical data support the rational combination of the 2 modalities and has paved way for the clinical development of the combination across a spectrum of cancers. In this review, we highlight the preclinical and clinical development of combined RT and PD-1/PD-L1 blockade to date. In addition to a comprehensive evaluation of available safety and efficacy data, we discuss important points of consideration in clinical trial design for this promising combination.
Exploratory genomic analysis of high-grade neuroendocrine neoplasms across diverse primary sites (2022)

High-grade (grade 3) neuroendocrine neoplasms (G3 NENs) have poor survival outcomes. From a clinical standpoint, G3 NENs are usually grouped regardless of primary site and treated similarly. Little is known regarding the underlying genomics of these rare tumors, especially when compared across different primary sites. We performed whole transcriptome (n = 46), whole exome (n = 40), and gene copy number (n = 43) sequencing on G3 NEN formalin-fixed, paraffin-embedded samples from diverse organs (in total, 17 were lung, 16 were gastroenteropancreatic, and 13 other). G3 NENs despite arising from diverse primary sites did not have gene expression profiles that were easily segregated by organ of origin. Across all G3 NENs, TP53, APC, RB1, and CDKN2A were significantly mutated. The CDK4/6 cell cycling pathway was mutated in 95% of cases, with upregulation of oncogenes within this pathway. G3 NENs had high tumor mutation burden (mean 7.09 mutations/MB), with 20% having >10 mutations/MB. Two somatic copy number alterations were significantly associated with worse prognosis across tissue types: focal deletion 22q13.31 (HR, 7.82; P = 0.034) and arm amplification 19q (HR, 4.82; P = 0.032). This study is among the most diverse genomic study of high-grade neuroendocrine neoplasms. We uncovered genomic features previously unrecognized for this rapidly fatal and rare cancer type that could have potential prognostic and therapeutic implications.
Hepatitis B virus X protein modulates peroxisome proliferator‐activated receptor γ through protein–protein interaction (2003)

Ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been reported to induce growth inhibition and apoptosis in various cancers including hepatocellular carcinoma (HCC). However, the effect of hepatitis B virus X protein (HBx) on PPARgamma activation has not been characterized in hepatitis B virus (HBV)-associated HCC. Herein, we demonstrated that HBx counteracted growth inhibition caused by PPARgamma ligand in HBx-associated HCC cells. We found that HBx bound to DNA binding domain of PPARgamma and HBx/PPARgamma interaction blocked nuclear localization and binding to recognition site of PPARgamma. HBx significantly suppressed a PPARgamma-mediated transactivation. These results suggest that HBx modulates PPARgamma function through protein-protein interaction.
Effects of laser peening on fatigue life in an arrestment hook shank application for naval aircraft (2011)

Laser peening is evaluated relative to and in combination with other means of improving fatigue resistance in a particularly severe arrestment hook shank application for a carrier-based Naval aircraft. A large-scale test specimen was designed and manufactured from Hy-Tuf steel to geometrically simulate conditions in the arrestment hook shank, and fatigue tests were conducted on peened specimens under conditions of spectrum loading that simulate aircraft arrestments. Laser peening substantially increases the resistance to crack initiation relative to conventional shot peening. A change to a higher-strength steel, Ferrium S53, significantly increases the crack initiation life of both conventionally shot peened and laser peened specimens, with the latter exhibiting the highest levels of crack initiation life for all conditions evaluated in this test program. Proof loading at levels above the design limit load, conducted before the peening operation, substantially increases the crack initiation life of conventionally shot peened specimens. In contrast, proof loading does not provide additional improvements in the fatigue life of laser peened specimens since the depth of plasticity due to proof loading is similar in magnitude to the depth of residual compressive stress introduced by laser peening. Finally, limited test results suggest that repeated laser peening over the life of a component may maximize or even extend crack initiation life; however, a significant amount of testing would be required to determine the processing parameters that maximize the efficacy of this approach to extending fatigue life.
Expanding the Morphologic Spectrum of Differentiated VIN (dVIN) Through Detailed Mapping of Cases With p53 Loss (2014)

The pathogenesis of vulvar squamous cell carcinoma follows 1 of 2 distinct pathways. A precursor lesion in the human papilloma virus-independent pathway, differentiated vulvar intraepithelial neoplasia (dVIN), was only recently characterized in detail and is infrequently diagnosed without an associated component of invasive carcinoma. Aberrant p53 immunostaining is frequently seen in dVIN, and in approximately 25% to 30% of cases it manifests as a complete loss or a p53-null pattern. The abrupt transition between p53 loss and basal p53 expression in lesional versus nonlesional epithelium allows clear demarcation between neoplastic and non-neoplastic epithelium. For this study, 14 specimens from 10 patients were identified from the pathology archives of 2 teaching hospitals on the basis of: (1) a diagnosis of dVIN, with or without invasive carcinoma; and (2) p53-null immunostaining pattern in lesional cells. Ten specimens had associated invasive carcinoma. All sections from each specimen that showed the specimen resection margin were stained for p53 and reviewed together with all hematoxylin and eosin sections. Detailed morphologic assessment of the p53-null epithelium was made and compared with the adjacent benign squamous epithelium. The status of the resection margins based on the original pathologic assessment was compared with that assessed with p53 immunohistochemistry. One specimen showed p53 loss in the invasive carcinoma but patchy basal positivity in the region originally diagnosed as dVIN, supporting interpretation as a benign hyperplastic focus, rather than dVIN. In the remaining 13 specimens the areas originally diagnosed as dVIN, as well as the associated invasive carcinoma (if present), were p53-null. In 8 of these specimens, on the basis of the presence of p53-null immunostaining and subtle morphologic abnormalities, dVIN was more extensive than originally recognized. The spectrum of morphologic changes in p53-null regions that were in continuity with areas originally recognized as dVIN were subtle and typically consisted of an abrupt change in maturation of the squamous epithelium (loss of keratohyaline granules and parakeratosis), tinctorial alterations in the keratinocytes, with cells containing more abundant eosinophilic cytoplasm, and minimal basal nuclear atypia. Margin status changed from negative to positive in 4 of 13 specimens and from focally to more extensively positive in an additional 3 specimens. In summary, the clonal in situ component of non-human papilloma virus vulvar squamous cell carcinoma can be characterized by very subtle morphologic abnormalities that may be misinterpreted as benign change. This results in underestimation of the extent of dVIN, and, as a result, resection margin involvement may be significantly underestimated. dVIN can also be overdiagnosed in areas of reactive change. Better tools for diagnosis of dVIN are needed; until such tools are developed the limitations in the current diagnosis of dVIN should be recognized.
Fluorescent and colorimetric magnetic microspheres as nanosensors for Hg2+ in aqueous solution prepared by a sol–gel grafting reaction and host–guest interaction (2013)

Fluorescent sensing TSRh6G-β-cyclodextrin fluorophore/adamantane-modified inclusion complex magnetic nanoparticles (TFIC MNPs) have been synthesized via the cooperation of a host-guest interaction and sol-gel grafting reaction. Powder X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, and UV-visible absorption and emission spectroscopy have been employed to characterize the material. Fluorescence and UV-visible spectra have shown that the resultant multifunctional nanoparticle sensors exhibit selective 'turn-on' type fluorescent enhancements and a clear color change from light brown to pink with Hg(2+). Owing to a larger surface area and high permeability, TFIC MNPs exhibit remarkable selectivity and sensitivity for Hg(2+), and its detection limit measures up to the micromolar level in aqueous solution. Most importantly, magnetic measurements have shown that TFIC magnetic nanoparticles are superparamagnetic and they can be separated and collected easily using a commercial magnet. These results not only solve the limitations in practical sensing applications of nanosensors, but also enable the fabrication of other multifunctional nanostructure-based hybrid nanomaterials.
Ig V region restrictions in human chronic lymphocytic leukemia suggest some cases have a common origin (2004)

The factors that contribute to the development of B cell chronic lymphocytic leukemia (B-CLL) are unknown, and the groups of individuals at the greatest risk for developing this common leukemia are not well defined. Molecular features are important for classifying cases of B-CLL, and it is now apparent that similarities among Ig rearrangements between patients may give important clues to the origin of this disease.
Effects of γ-ray Irradiation on Thiodiglycolamide-type Extractant-impregnated Adsorbents for Separation of Platinum Group Metals from High-level Liquid Waste (2017)

To estimate the applicability of thiodiglycolamide-type extractant-impregnated adsorbents to separation of the platinum group metals (PGMs) from high-level liquid waste, radiation effects on the adsorption behavior of PGMs onto a macroporous silica-based (Crea-TOA)/SiO2-P absorbent and on the stability of the adsorbent were investigated by using γ-rays emitted from 60Co, and the results were compared with those obtained using (MOTDGA-TOA)/SiO2-P. A difference in adsorption behaviors of PGMs onto the two adsorbents was not observed with or without irradiation up to 100 kGy of the absorbed dose. Decomposition of the impregnated extractants and degradation of the adsorption capability increased with increasing absorbed dose, but the distribution coefficient of Pd remained >102 up to approximately 250 kGy. The retention ratio of loaded PGMs gradually decreased with increasing absorbed dose. From these results, the adsorbents were considered to be useful for the adsorption of PGMs irrespective of whether the adsorption system was irradiated, except for when the adsorbent was irradiated by a very large dose.
Magnetic resonance imaging using a ribbonator: Hand and wrist (1989)

A modified version of a single-turn solenoid with rectangular symmetry, which we call a ribbonator, provides excellent magnetic resonance images of the hand and wrist when used as both the transmitter and the receiver in a 1.5-T clinical imaging system. The very high RF efficiency provides excellent signal-to-noise and anatomical resolution. Design equations and RF properties of the resonator are discussed.
More Is Better: Large Scale Partially-supervised Sentiment Classification - Appendix (2012)

We describe a bootstrapping algorithm to learn from partially labeled data, and the results of an empirical study for using it to improve performance of sentiment classification using up to 15 million unlabeled Amazon product reviews. Our experiments cover semi-supervised learning, domain adaptation and weakly supervised learning. In some cases our methods were able to reduce test error by more than half using such large amount of data. NOTICE: This is only the supplementary material.
FFT/IFFT Based Blind SIMO Channel Identiflcation (2008)

This paper presents an FFT/IFFT based blind identiflcation method for estimating the flnite im- pulse response of single-input multiple-output chan- nels driven by an unknown deterministic signal. The proposed algorithm successfully handles a very small size of received data, for which the existing blind channel estimation methods, including the subspace, cross-relation and shifted correlation algorithms, are known to be inefiective. Moreover, with no assump- tion of the precise knowledge of channel order, the proposed algorithm is capable of estimating channel parameters as well as detecting channel order. Sim- ulations show that the proposed algorithm outper- forms the existing methods in small sample size situ- ations. knowledge of the channel order and achieves channel parameter identiflcation and order (over)estimation. Despite difierent individual strengths, these methods share a common deflciency - they become inefiective when the observation data size is very small. This issue needs addressing because in practical commu- nication applications, there exist situations where a long data sequence is unavailable. In this paper, we present a novel blind SIMO chan- nel identiflcation method targeted at a small size of observation data. Motivated by the CR between each channel output pair, which serves as the basis of the CR approach (4), we extend the CR property to the frequency domain via the discrete Fourier trans- form (DFT) and take advantage of the computational e-ciency of the fast Fourier transform (FFT). The new method makes two contributions to blind chan- nel identiflcation. First, with a null guard interval introduced in the input, the proposed algorithm re- quires less observation data than the existing meth- ods, and a single short-duration output block su-ces for channel identiflcation. Second, assuming only the knowledge of the upper bound of channel order, the proposed algorithm is capable of estimating channel parameters as well as detecting channel order. In the case when channel order is unknown, compared to the SC approach (5) (6), our method performs better in small sample size scenarios. With FSC, the pro- posed algorithm provides a substantial performance improvement over the SC approach in the high SNR region.
Catalytic Oxidation of Hydrazo Derivatives Promoted by a TiCl3/HBr System (2007)

Through a novel catalytic process of general synthetic interest, hydrazo compounds were efficiently and selectively converted into corresponding azo derivatives. The proposed mechanism of this process comprises two separate and distinctive catalytic cycles, linked together by radical species. The first cycle includes formation of a hydroxy radical, generated by Ti(III) single-electron reduction of H2O2. In the second cycle, the hydroxy radical oxidizes HBr into hypobromous acid, which in turn is reduced back to HBr and water by a hydrazo substrate.
Microbial Dynamics in Oil-Impacted Prairie Soil (1999)

A remote site in the Tallgrass Prairie Preserve (Osage County, OK) was contaminated with crude oil by a pipeline break in 1992. In 1996, the contaminated soil was bioremediated by blending with uncontaminated soil, prairie hay, buffalo manure, and commercial fertilizers, and spreading in a shallow layer over uncontaminated soil to create a landfarm. The landfarm was monitored for two years for aerobic and anaerobic bacteria, soil gases indicative of microbial activity, and for changes in the concentration of total petroleum hydrocarbons (TPH). Levels of hydrocarbon degraders and soil gas indicators of aerobic degradation were stimulated in the landfarm during the first warm season relative to uncontaminated prairie soil. However, these same indicators were less conclusive during the second warm season, indicating depletion of the more easily degradable hydrocarbons, although the landfarm still contained 6,800 mg/kg TPH on the average at the beginning of the second warm season. Methane formation and methanogen counts were clearly stimulated in the first warm season relative to uncontaminated prairie soil, indicating that methanogenesis plays an important role in the mineralization of hydrocarbons even in these shallow soils.
A general method for the selection of high-level scFv and IgG antibody expression by stably transfected mammalian cells (2008)

The isolation of mammalian cell lines capable of high-yield expression of recombinant antibodies is typically performed by screening multiple individual clones by limiting dilution techniques. A number of experimental strategies have recently been devised to identify high-expressing clones, but protocols are often difficult to implement, time consuming, costly and limited in terms of number of clones which can be screened. In this article, we describe new vectors for the expression of recombinant antibodies in IgG format and in other formats, based on the single-chain Fv module, as well as a high-throughput screening procedure, based on the direct staining of antibodies transiting the membrane of a stably transfected cell, followed by preparative sorting using a high-speed cell sorter. This procedure allows, in one step, to deposit single cells into individual wells of a 96-well microtiter plate (thus facilitating cloning) and to preferentially recover those rare cell populations which express dramatically higher levels of recombinant antibody. Using cell cultures followed by affinity purification techniques, we could confirm that the new vectors and the new screening procedure reliably yield high-expression clones and homogenous protein preparations. We expect that these techniques should find broad applicability for both academic and industrial antibody engineering research.
Properties of Electrical Discharge Machinable SiC-TiB₂ Composites (1995)

Electrical discharge machinable SiC-TiB₂ composites were fabricated by hot-pressing. Their mechanical and electrical properties were determined as a function of TiB₂ content. The addition of TiB₂ to SiC matrix increased the strength and toughness and decreased electrical resistivity. The flexural strength and fracture toughness of SiC-40 vol% TiB₂ composites were approximately 50% higher than those of monolithic SiC ceramics. Microstructural analysis showed that the toughening was mainly due to the crack deflection, with some possible contribution from crack branching or microcracking.
Nicotinamide Mononucleotide Administration Triggers Macrophages Reprogramming and Alleviates Inflammation During Sepsis Induced by Experimental Peritonitis (2022)

Peritonitis and subsequent sepsis lead to high morbidity and mortality in response to uncontrolled systemic inflammation primarily mediated by macrophages. Nicotinamide adenine dinucleotide (NAD+) is an important regulator of oxidative stress and immunoinflammatory responses. However, the effects of NAD+ replenishment during inflammatory activation are still poorly defined. Hence, we investigated whether the administration of β-nicotinamide mononucleotide (β-NMN), a natural biosynthetic precursor of NAD+, could modulate the macrophage phenotype and thereby ameliorate the dysregulated inflammatory response during sepsis. For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity. β-NMN was administered for 4 days after CLP and for 3 days post thioglycolate treatment where peritoneal macrophages were subsequently analyzed. In the CLP model, administration of β-NMN decreased bacterial load in blood and reduced clinical signs of distress and mortality during sepsis. These results were supported by transcriptomic analysis of hearts and lungs 24 h post CLP-induction, which revealed that β-NMN downregulated genes controlling the immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria, and autophagy. In the thioglycolate model, a significant increase in the proportion of CD206 macrophages, marker of anti-inflammatory M2 phenotype, was detected on peritoneal exudate macrophages from β-NMN-administered mice. Transcriptomic signature of these macrophages after bacterial stimulation confirmed that β-NMN administration limited the pro-inflammatory M1 phenotype and induced the expression of specific markers of M2 type macrophages. Furthermore, our data show that β-NMN treatment significantly impacts NAD + metabolism. This shift in the macrophage phenotype and metabolism was accompanied by a reduction in phagolysosome acidification and secretion of inflammatory mediators in macrophages from β-NMN-treated mice suggesting a reduced pro-inflammatory activation. In conclusion, administration of β-NMN prevented clinical deterioration and improved survival during sepsis. These effects relied on shifts in the metabolism of organs that face up an increased energy requirement caused by bacterial infection and in innate immunity response, including reprogramming of macrophages from a highly inflammatory phenotype to an anti-inflammatory/pro-resolving profile.