gebhart/patrepeval huggingface dataset:
Abstract PO-097: High resolution analysis of clonal dynamics using lineage tracing and single cell transcriptomics (2020)

Abstract The immense evolutionary capacity of cancer poses major challenges to current therapeutic efforts, and results from the vast clonal heterogeneity and ability of individual cancer cells to adapt to diverse selective pressures. More complete mechanistic understanding of the basis of therapeutic resistance has been limited by difficulties in coupling genetic identity of cells to their respective transcriptomic and functional outputs. To this end, we developed a novel high-complexity expressed barcode system, ClonMapper, that integrates DNA barcoding with single-cell RNA-sequencing and clonal isolation to characterize thousands of clones within a mixed cancer cellpopulation. In applying this system to breast cancer and B cell cancer cell lines in the setting of resistance to doxorubicin and fludarabine-based chemotherapy, we discover pretreatment sub-populations with distinct expression profiles that not only confer distinct treatment survivorship trajectories, but also provide the basis for long-term clonal equilibrium between co-existing clones in the absence of treatment. These data reveal the diverse clonal characteristics and therapeutic responses of a heterogeneous cancer cell population and highlight the unprecedented resolution that can be achieved using ClonMapper. Citation Format: Eric A. Brenner, Daylin Morgan, Aziz Al'Khafaji, Catherine Gutierrez, Catherine J. Wu, Amy Brock. High resolution analysis of clonal dynamics using lineage tracing and single cell transcriptomics [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-097.
SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy (2016)

Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride. Moreover, we show that over-expression of PNPLA8 dramatically decreases hepatic steatosis through increased autophagy in hepatocytes of HFD-fed mice. Live-cell imaging analyses also reveal that PNPLA8 dynamically interacts with LC3 and we suggest that the SREBP-2/PNPLA8 axis represents a novel regulatory mechanism for lipid homeostasis. These data provide a possible mechanism for the reported beneficial effects of statins for decreasing hepatic triglyceride levels in NAFLD patients.
Posttranslational Modifications of Rat Proenkephalin Overexpressed in Chinese Hamster Ovary Cells* (1991)

Rat proenkephalin was overexpressed in Chinese hamster ovary cells using the dihydrofolate reductase-coupled genetic amplification method. About 2 mg purified protein could be obtained from 250 ml conditioned medium; multiple successive harvests could be obtained from the same roller bottle. Degradation of proenkephalin released into the conditioned medium was reduced significantly in the presence of 2% fetal bovine serum. Forty-eight percent of recombinant proenkephalin was glycosylated; glycosylation could be entirely prevented by the addition of tunicamycin. Two-dimensional isoelectric focusing experiments showed that recombinant proenkephalin exhibited considerable charge heterogeneity, with two major unglycosylated isoelectric forms and six or seven glycosylated isoelectric forms. The estimated isoelectric points of the major unglycosylated proenkephalins were 6.0 and 6.1, while glycosylated proenkephalins ranged in pI from 5.7-6.1. Some of this isoelectric heterogeneity is due to phosphorylation; [32P] orthophosphate was readily incorporated into serine residues within newly synthesized proenkephalin.
Extracting Co-locator context (2009)

Having reliable context sources is very important for context-aware applications and the devices around a user can be a useful context for many applications. While the importance of ‘devices around’ as a context has been highlighted many times, to the best of our knowledge, there is no systematic me
Gas–liquid flows through porous media in microgravity: Packed Bed Reactor Experiment‐2 (2022)

Abstract Modifications were made to the Packed Bed Reactor Experiment (PBRE) and flown on the International Space Station as PBRE‐2 to eliminate external pressure oscillations at higher liquid flow rates and the packing diameter was reduced to increase the pressure gradient for lower flows. It is found that gas hold‐up is a function of bed history at low liquid and gas flow rates whereas higher gas hold‐up and pressure gradients are observed for the test conditions following a liquid only pre‐flow compared to the test conditions following a gas only pre‐flow period. Over the range of flow rates tested, the capillary force is the dominant contributor to the pressure gradient, which is found to be linear with the superficial liquid velocity but is a much weaker function of the superficial gas velocity and varies inversely with the particle diameter.
Microemulsion mediated synthesis of BaTi03-Ag nanocomposites (2009)

BaTiO3 - Ag composite nanopowders were synthesized via microemulsion mediated synthesis through the hydrolytic decomposition of mixed metal alkoxide solutions as precursor for the BaTiO3 and the reduction of silver nitrate in the presence of polyvinylpyrrolidone (PVP) as source for the Ag nanoparticles. The X-ray diffraction (XRD) patterns indicate that BaTiO3 and Ag phases were successfully synthesized in the composite powders. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) show that the synthesized BaTiO3 nanoparticles were aggregates of nanosized primary particles as small as 10 nm in diameter and the average particle size of nanocrystalline Ag was about 100 nm. Calcination and sintering studies reveal that there exists a difference in the sintering behaviour of BaTiO3 and Ag in the composite nanopowders. Thermogravimetric analysis (TGA) shows weight losses due to the burnout of organic residues arising from the synthesis, the release of water from the surface and separation of hydroxyl ions from the lattice of BaTiO3 nanoparticles. A dilatometric study of BaTiO3-Ag composite confirmed a strong difference in the shrinkage behaviour compared to that of the pure BaTiO3 obtained by microemulsion mediated synthesis. .
Suitability of MgB/sub 2/ tapes with iron sheaths for multiturn superconducting coils (2003)

This paper investigates the suitability of MgB/sub 2/ tapes clad in a high magnetic permeability iron sheath for use in practical multi-turn superconducting coils. The flux-density in the MgB/sub 2/ portion of a single filamentary tape under various configurations is analyzed and its effect on the critical current capability is evaluated. The magnetic field is computed numerically using the finite element (FE) method. The FE model used for the analysis is described along with the assumptions made. The results indicate that the iron-clad MgB/sub 2/ tapes are undesirable for SC coils in many practical applications from a steady state performance stand point.
Stunting Is Preceded by Intestinal Mucosal Damage and Microbiome Changes and Is Associated with Systemic Inflammation in a Cohort of Peruvian Infants (2019)

Stunting, defined as height-for-age <i>Z</i> score equal to or lower than -2, is associated with increased childhood mortality, cognitive impairment, and chronic diseases. The aim of the study was to investigate the relationship between linear growth, intestinal damage, and systemic inflammation in infants at risk of stunting. We followed up 78 infants aged 5-12 months living in rural areas of Peru for 6 months. Blood samples for biomarkers of intestinal damage (intestinal fatty-acid-binding protein [I-FABP] and zonulin) and systemic inflammation (interleukin-1β, interleukin-6, tumor necrosis factor α [TNF-α], soluble CD14, and lipopolysaccharide-binding protein [LBP]) and fecal samples for microbiome analysis were collected at baseline and closure of the study. The children's growth and health status were monitored through biweekly home visits by trained staff. Twenty-one percent of the children became stunted: compared with non-stunted children, they had worse nutritional parameters and higher levels of serum I-FABP at baseline. The likelihood of becoming stunted was strongly associated with an increase in sCD14 over time; LBP and TNF-α showed a trend toward increase in stunted children but not in controls. The fecal microbiota composition of stunted children had an increased beta diversity compared with that of healthy controls throughout the study. The relative abundance of <i>Ruminococcus 1</i> and <i>2</i>, <i>Clostridium sensu stricto</i>, and <i>Collinsella</i> increased in children becoming stunted but not in controls, whereas <i>Providencia</i> abundance decreased. In conclusion, stunting in our population was preceded by an increase in markers of enterocyte turnover and differences in the fecal microbiota and was associated with increasing levels of systemic inflammation markers.
Sustainable Discovery and Development of Antibiotics — Is a Nonprofit Approach the Future? (2019)

Shifting to a nonprofit-driven model for development of antibiotics could encourage discovery and development of truly needed drugs that improve patient outcomes and permit more effective control over the postapproval use of antibiotics to prolong their effectiveness.
Guest Editorial Special Issue on Large-Scale Evolutionary Multiobjective Optimization and Its Practical Applications (2023)

Complex optimization problems with hundreds or even thousands of decision variables and dozens of conflicting objectives are not uncommon in the real world. In the past five years, increased research efforts have been dedicated to large-scale multiobjective optimization problems (LSMOPs) by using a variety of search strategies, including variable grouping, variable analysis, problem transformation, dimensionality reduction, and novel recombination operators. Despite the success of these efforts in solving some general LSMOPs, there still remains a big gap between the LSMOPs that have been addressed and those encountered in real life, such as sparse, highly constrained, dynamic, and expensive LMOPs, as well as very large-scale and many-objective optimization problems that are widely seen and of paramount importance for solving scientific and engineering problems. Due to the significant practical importance of large-scale multiobjective optimization, there is a high demand for computationally efficient and effective evolutionary algorithms for solving LSMOPs.
Distinct roles of ORAI1 in T cell–mediated allergic airway inflammation and immunity to influenza A virus infection (2022)

T cell activation and function depend on Ca<sup>2+</sup> signals mediated by store-operated Ca<sup>2+</sup> entry (SOCE) through Ca<sup>2+</sup> release-activated Ca<sup>2+</sup> (CRAC) channels formed by ORAI1 proteins. We here investigated how SOCE controls T cell function in pulmonary inflammation during a T helper 1 (T<sub>H</sub>1) cell-mediated response to influenza A virus (IAV) infection and T<sub>H</sub>2 cell-mediated allergic airway inflammation. T cell-specific deletion of <i>Orai1</i> did not exacerbate pulmonary inflammation and viral burdens following IAV infection but protected mice from house dust mite-induced allergic airway inflammation. ORAI1 controlled the expression of genes including p53 and E2F transcription factors that regulate the cell cycle in T<sub>H</sub>2 cells in response to allergen stimulation and the expression of transcription factors and cytokines that regulate T<sub>H</sub>2 cell function. Systemic application of a CRAC channel blocker suppressed allergic airway inflammation without compromising immunity to IAV infection, suggesting that inhibition of SOCE is a potential treatment for allergic airway disease.
Overexpression of human decoy receptor 3 in mice results in a systemic lupus erythematosus–like syndrome (2007)

These results show that DcR3 overexpression could lead to an SLE-like syndrome in mice.
BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1 (2017)

BET inhibitors (BETi) target bromodomain-containing proteins and are currently being evaluated as anti-cancer agents. We find that maximal therapeutic effects of BETi in a Myc-driven B cell lymphoma model required an intact host immune system. Genome-wide analysis of the BETi-induced transcriptional response identified the immune checkpoint ligand Cd274 (Pd-l1) as a Myc-independent, BETi target-gene. BETi directly repressed constitutively expressed and interferon-gamma (IFN-γ) induced CD274 expression across different human and mouse tumor cell lines and primary patient samples. Mechanistically, BETi decreased Brd4 occupancy at the Cd274 locus without any change in Myc occupancy, resulting in transcriptional pausing and rapid loss of Cd274 mRNA production. Finally, targeted inhibition of the PD-1/PD-L1 axis by combining anti-PD-1 antibodies and the BETi JQ1 caused synergistic responses in mice bearing Myc-driven lymphomas. Our data uncover an interaction between BETi and the PD-1/PD-L1 immune-checkpoint and provide mechanistic insight into the transcriptional regulation of CD274.
Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism (2003)

The DJ-1 gene was identified as responsible for early onset autosomal recessive parkinsonism in two families (PARK7). In this study, after excluding mutations in the parkin gene, the authors screened a large series of early onset autosomal recessive parkinsonism families and consanguineous isolated patients of diverse geographic origins for DJ-1 mutations. No mutations were found. This indicates that PARK7 is not a common locus for early onset autosomal recessive parkinsonism, and that one or more new loci remains to be identified.
Accurate analysis and low-complexity compensation of transceiver nonlinear distortion for higher-order modulation (2022)

As network traffic increases continuously, advances in spectral efficiency with higher-order modulation formats, such as 64 and 256 quadrature amplitude modulation (64-QAM and 256-QAM, respectively), are expected. The device nonlinearity is a major obstacle in achieving a higher-order modulation which requires a high signal-power-to-noise ratio and a low waveform distortion. In this study, we analyze the characteristics of device nonlinearity and its impact on the performance of a coherent transceiver. Furthermore, we demonstrate a low-complexity nonlinear compensation that operates on a symbol rate basis and that can handle higher-order modulations such as 64-QAM or beyond.
Model-based estimation of ethanol content in flexible fuel vehicles (2011)

Presented in this paper is a model-based method for accurately estimating the percent ethanol content of an ethanol-gasoline fuel blend used in flexible fuel vehicles (FFVs). Few methods exist in literature addressing the problem of ethanol estimation in production FFVs. The proposed approach has a distinct advantage as it uses the existing sensor set on a production vehicle. Measurements from the sensors are used to adapt a steady state parametric model relating the engine speed, throttle angle opening and the air-fuel ratio to the fuel injector pulse width command. A first-principles physics-based approach is used to develop the model structure. The fuel composition information is embedded in the adapted model coefficients whose variation is used for ethanol content estimation. The method is validated with experiments on a 2005 Ford 5.4-L V8 port fuel injected engine.
Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome (2010)

The availability of useful animal models reflecting the human obesity syndrome is crucial in the search for novel compounds for the pharmacological treatment of obesity. In the current study, we have performed an extensive characterization of the obesity syndrome in a polygenetic animal model, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization including blood biochemistry and glucose homeostasis was examined at 2, 3, 6, and 9 months of age. Furthermore, in 6-month-old HE-fed DIO rats, the anti-obesity effects of liraglutide and sibutramine were examined in a 28-day study. Only HE-fed DIO rats developed visceral obesity, hyperleptinemia, hyperinsulinemia, and dyslipidemia, and showed a worsening of glucose tolerance over time. In line with the hyperlipidemic profile, a severe hepatic fat infiltration was observed in DIO rats at 6 months of age. The effects of liraglutide and sibutramine were tested in 6-month-old DIO rats. Both compounds effectively reduced food intake and body weight in DIO rats. Liraglutide furthermore improved glucose tolerance when compared with sibutramine. Our data highlights the usefulness of a polygenetic animal model for screening of compounds affecting food intake, body weight, and glucose homeostasis. Furthermore, the results underscore the effectiveness of GLP-1 mimetics both as anti-diabetes and anti-obesity agents.
Alternative Developer Solutions and Processes for EUV and ArFi Lithography (2019)

The application of alternative developers for both extreme ultraviolet (EUV) and 193-nm immersion (“ArFi”) lithography is investigated by focusing on their effects on the “Defect-Not-Found” (DNF) margins. In case of EUV lithography, defects primarily comprise line bridging at the underdose region and line breaks at the overdose region. The application of a 0.26-N tetrabutylammonium hydroxide (TBAH) developer solution when compared to that of a 0.26-N tetramethylammonium hydroxide (TMAH) developer solution resulted in improved resist sensitivity while maintaining the same DNF margin. In case of ArFi lithography, defects primarily comprise line bridging at the underdose region and pattern collapse at the overdose region. The same improvement that has been mentioned above can be observed with respect to the resist sensitivity using the TBAH developer solution. However, the TBAH developer solution significantly minimizes the pattern collapse at the overdose region, further extending the minimum line pattern size. This translated to significant improvements in both the exposure latitude (EL) and overdose margin (OM) and resulted in a significant increase in the DNF margin. Furthermore, the application of a non-ionic surfactant type additive on the TMAH developer solution demonstrates resist sensitivity improvement and pattern collapse mitigation. Increased EL and OM values were observed, which also resulted in increased DNF margin. Results indicate the advantages of utilizing alternative developer solutions in improving the DNF margins.
Improving diesel engine efficiency at high speeds and loads through improved breathing via delayed intake valve closure timing (2017)

Valve train flexibility enables optimization of the cylinder-manifold gas exchange process across an engine’s torque/speed operating space. This study focuses on the diesel engine fuel economy improvements possible through delayed intake valve closure timing as a means to improve volumetric efficiency at elevated engine speeds via dynamic charging. It is experimentally and analytically demonstrated that intake valve modulation can be employed at high-speed (2200 r/min) and medium-to-high load conditions (12.7 and 7.6 bar brake mean effective pressure) to increase volumetric efficiency. The resulting increase in inducted charge enables higher exhaust gas recirculation fractions without penalizing the air-to-fuel ratio. Higher exhaust gas recirculation fractions allow efficiency improving injection advances without sacrificing NOx. Fuel savings of 1.2% and 1.9% are experimentally demonstrated at 2200 r/min for 12.7 and 7.6 bar brake mean effective pressure operating conditions via this combined strategy of delayed intake valve closure, higher exhaust gas recirculation fractions, and earlier injections.
Intraoral Mitochondrial-Targeted GS-Nitroxide, JP4-039, Radioprotects Normal Tissue in Tumor-Bearing Radiosensitive Fancd2–/– (C57BL/6) Mice (2016)

We evaluated normal tissue specific radioprotection of the oral cavity in radiosensitive Fanconi Anemia (FA) Fancd2(-/-) mice with orally established tumors using mitochondrial-targeted GS-nitroxide (JP4-039). Adult (10-12 weeks old) Fancd2(+/+), Fancd2(+/-) and Fancd2(-/-) mice (C57BL/6 background) and subgroups with orally established TC-1 epithelial cell tumors received a single fraction of 28 Gy or four daily fractions of 8 Gy to the head and neck. Subgroups received JP4-039 in F15 emulsion (F15/JP4-039; 0.4 mg/mouse), 4-amino-Tempo in F15 emulsion (F15/4-amino-Tempo; 0.2 mg/mouse) or F15 emulsion alone prior to each irradiation. Oral mucosa of Fancd2(-/-) mice showed baseline elevated RNA transcripts for Sod2, p53, p21 and Rad51 (all P < 0.0012) and suppressed levels of Nfkb and Tgfb, (all P < 0.0020) compared with Fancd2(+/+) mice. The oral mucosa in tumor-bearing mice of all genotypes showed decreased levels of p53 and elevated Tgfb and Gadd45a (P ≤ 0.0001 for all three genotypes). Intraoral F15/JP4-039, but not F15/4-amino-Tempo, modulated radiation-induced normal tissue transcript elevation, ameliorated mucosal ulceration and reduced the depletion of antioxidant stores in oral cavity tissue of all genotypes, but did not radioprotect tumors. Mitochondrial targeting makes F15/JP4-039 an effective normal tissue radioprotector for Fancd2(-/-) mice, as well as wild-type mice.