julilili42/papers huggingface dataset:
Phenotypic plasticity in response to temperature fluctuations is genetically variable, and relates to climatic variability of origin, in Arabidopsis thaliana
2018-07-01

Under current climate change, increasing mean temperatures are not only causing hotter summers, but temperature variability is increasing as well. Phenotypic plasticity can help plants to overcome negative effects of temperature variability and allow them to rapidly adjust traits to adverse conditions. Moreover, genetic variation in such plasticity could provide potential for adaptive evolution in response to changing climate variability. Here, we conducted an experiment with 11 Arabidopsis thaliana genotypes to investigate intraspecific variation in plant responses to two aspects of variable temperature stress: timing and frequency. We found that the timing but not frequency of temperature stress affected the phenology, growth, reproduction and allocation strategy of plants, and that genotypes differed substantially in their responses. Moreover, trait plasticity was positively related to precipitation variability of origin, suggesting an adaptive role of plasticity. Our results indicate that the developmental stage of a plant during heat stress is a key determinant of its response, and that plasticity to temperature variability is an evolving and possibly adaptive trait in natural populations of A. thaliana. More generally, our study demonstrates the usefulness of studying plant responses to climatic variability per se, given that climatic variability is predicted to increase in the future.
Reliability of Novel Ceramic Encapsulation Materials for Electronic Packaging
2018-07-01

Abstract Enhancements on power electronic systems with reduced chip area and miniaturized passive components are subject of several research activities in academics and industry. To realize such future electronic devices, it is necessary to incorporate wide bandgap semiconductor technology such as silicon carbide and gallium nitride operating at higher temperatures. Therefore, the development of novel materials with high thermal conductivities and stability, withstanding harsh environments up to 300°C is of major interest. Especially, polymeric encapsulation materials have to be improved because of common degradation effects above 175°C. Ceramic (nonpolymeric) materials with thermal conductivities above 5 W/(m·K) already illustrated promising results for the encapsulation of power electronics. The present work illustrates recent developments and improvements on novel ceramic encapsulation materials, which finally avoid critical interactions with the chip surface. Furthermore, advances in reliability will be discussed in terms of passed high-temperature reverse bias and humidity tests correlated with relevant material properties.
Slow Long‐Term Exhumation of the West Central Andean Plate Boundary, Chile
2018-07-01

Abstract We present a regional analysis of new low‐temperature thermochronometer ages from the Central Andean fore arc to provide insights into the exhumation history of the western Andean margin. To derive exhumation rates over 10 million‐year timescales, 38 new apatite and zircon (U‐Th)/He ages were analyzed along six ~500‐km long near‐equal‐elevation, coast parallel, transects in the Coastal Cordillera (CC) and higher‐elevation Precordillera (PC) of the northern Chilean Andes between latitudes 18.5°S and 22.5°S. These transects were augmented with age‐elevation profiles where possible. Results are synthesized with previously published thermochronometric data, corroborating a previously observed trenchward increase in cooling ages in Peru and northern Chile. One‐dimensional thermal‐kinematic modeling of all available multichronometer equal‐elevation samples reveals mean exhumation rates of &lt;0.2 km/Myr since ~50 Ma in the PC and ~100 Ma in the CC. Regression of pseudovertical age‐elevation transects in the CC yields comparable rates of ~0.05 to ~0.12 km/Myr between ~40 and 80 Ma. Differences between the long‐term mean 1‐D rates and shorter‐term age‐elevation‐derived rates indicate low variability in the exhumation history. Modeling results suggest similar background exhumation rates in the CC and PC; younger ages in the PC are largely a function of increased heat flow and consequently an elevated geothermal gradient near the arc. Slow exhumation rates are suggestive of semiarid conditions across the region since at least the Eocene and deformation and development of the Andean fore arc around this time.
You say 'what', i hear 'where' and 'why'
2018-07-01

SQL declaratively specifies what the desired output of a query is. This work shows that a non-standard interpretation of the SQL semantics can, instead, disclose where a piece of the output originated in the input and why that piece found its way into the result. We derive such data provenance for very rich SQL dialects---including recursion, windowed aggregates, and user-defined functions---at the fine-grained level of individual table cells. The approach is non-invasive and implemented as a compositional source-level SQL rewrite: an input SQL query is transformed into its own interpreter that wields data dependencies instead of regular values. We deliberately design this transformation to preserve the shape of both data and query, which allows provenance derivation to scale to complex queries without overwhelming the underlying database system.
A unified manifold framework for efficient BRDF sampling based on parametric mixture models
2018-07-01

&lt;p&gt;Virtually all existing analytic BRDF models are built from multiple functional components (e.g., Fresnel term, normal distribution function, etc.). This makes accurate importance sampling of the full model challenging, and so current solutions only cover a subset of the model&#39;s components. This leads to sub-optimal or even invalid proposed directional samples, which can negatively impact the efficiency of light transport solvers based on Monte Carlo integration. To overcome this problem, we propose a unified BRDF sampling strategy based on parametric mixture models (PMMs). We show that for a given BRDF, the parameters of the associated PMM can be defined in smooth manifold spaces, which can be compactly represented using multivariate B-Splines. These manifolds are defined in the parameter space of the BRDF and allow for arbitrary, continuous queries of the PMM representation for varying BRDF parameters, which further enables importance sampling for spatially varying BRDFs. Our representation is not limited to analytic BRDF models, but can also be used for sampling measured BRDF data. The resulting manifold framework enables accurate and efficient BRDF importance sampling with very small approximation errors.&lt;/p&gt;
Precise predictions for electroweakino-pair production in association with a jet at the LHC
2018-07-01

A bstract We present the full NLO SUSY-QCD corrections to the pair production of neutralinos and charginos at the LHC in association with a jet and their matching to partonshower programs in the framework of the POWHEG-BOX package. The code we have developed provides a SUSY Les Houches Accord interface for setting electroweak and supersymmetric input parameters. Decays of the neutralinos and charginos and parton-shower effects can be simulated with multi-purpose programs such as PYTHIA. The capabilities of the code are illustrated by phenomenological results for a parameter point in the framework of pMSSM10, compatible with present experimental limits on supersymmetry. We find that NLO-QCD corrections as well as parton-shower effects are of primary importance for the appropriate description of jet distributions.
Individual Differences in Uncertainty Tolerance Are not Associated With Cognitive Control Functions in the Flanker Task
2018-07-01

Abstract. Cognitive control refers to the ability to make correct decisions concurrent to distracting information, and to adapt to conflicting stimulus configurations, eventually promoting goal-directed behavior. Previous research has linked individual differences in cognitive control to psychopathological conditions such as anxiety. However, a link with uncertainty tolerance (UT) has not been tested so far, although both constructs describe cognitive and behavioral performance in ambiguous situations, thus they share some similarities. We probed cognitive control in web-based experimentation (jsPsych) with a simple flanker task (N = 111) and a version without confounds in episodic memory (N = 116). Both experiments revealed two well-established behavioral indices: congruency effects (CEs) and congruency-sequence effects (CSEs). Only small-to-zero correlations emerged between CEs, UT, and need for cognitive closure (NCC), a personality trait inversely related to UT. A subtle correlation (r = .18) was noted in Experiment 2 between NCC and CSE. Throughout, Bayesian analyses provided anecdotal-to-moderate evidence for the null-hypotheses.
A two-step indirect inference approach to estimate the long-run risk asset pricing model
2018-07-01

Abstract The long-run consumption risk model provides a theoretically appealing explanation for prominent asset pricing puzzles, but its intricate structure presents a challenge for econometric analysis. This paper proposes a two-step indirect inference approach that disentangles the estimation of the model’s macro-economic dynamics and the investor’s preference parameters. A Monte Carlo study explores the feasibility and efficiency of the estimation strategy. We apply the method to recent U.S. data and provide a critical re-assessment of the long-run risk model’s ability to reconcile the real economy and financial markets. This two-step indirect inference approach is potentially useful for the econometric analysis of other prominent consumption-based asset pricing models that are equally difficult to estimate.
Abstract LB-369: In vivo imaging of tumor senescence with a novel beta-galactosidase specific PET tracer
2018-07-01

Abstract Senescence is a response to cellular stress and induces a durable cell cycle arrest, which has essential effects on metabolism as well as treatment outcome in cancer. Therefore the development of a diagnostic tool to detect senescent cells in vivo in cancer patients is of great interest. Here, the development of a novel PET tracer for non-invasive imaging of beta-galactosidase as a surrogate marker for senescence is described. Three different in vitro models were used to test the tracer. In HCT116 cells senescence was induced by doxorubicin, while in an HRas driven liver progenitor cell line it was induced by a doxycycline-dependent p53-specific shRNA. Finally, in a hepatocellular carcinoma cell line a ribosomal checkpoint inhibitor (RCI) was used for senescence induction. After incubation of the senescent cell lines with the tracer, we measured the activity of the cells in a gamma-counter, to assess the tracer uptake. For in vivo studies, the in vitro tested cells lines were injected s.c. in mice. These xenograft tumor bearing mice were treated with doxorubicin, doxycycline or RCI for senescence induction, depending on the cell line used. After i.v. injection of the tracer, PET/MR scans were performed to assess tracer uptake in the tumors (% of the injected dose/cc; %ID/cc) and tumor-to-muscle ratios. In vitro tracer uptake was significantly increased in all three cellular models used, compared to the respective control cells. The strongest increase was observed in the hepatocellular carcinoma cell line with an increase from 0.06 %ID/106 cells in control cells to 0.21 %ID/106 cells in senescent cells. In vivo PET/MRI revealed an enhanced tracer uptake in mice bearing HCT116 tumors after senescence induction (1.7 %ID/cc) compared to mice without senescence inducing treatment (1.1 %ID/cc). In the HRas model, the tracer uptake in senescent tumors was increased from 0.9 %ID/cc in control tumors to 1.5 %ID/cc in senescent tumors and in the hepatocellular carcinoma model we could observe an increase from 0.6 %ID/cc in control mice to 1.1 %ID/cc in treated mice. Ex vivo beta-galactosidase staining and immunohistology of tumor tissue confirmed induction of senescence. In this study we were able to show an increased uptake of our novel beta-galactosidase specific PET tracer in vitro in senescent cells as well as in vivo in murine xenograft tumor models. Therefore our tracer could become the first tool for non-invasive detection of senescence in patients. First-in-man studies are currently being prepared. Citation Format: Marcel A. Krueger, Jonathan M. Cotton, Benyuan Zhou, Katharina Wolter, Anna Kuehn, Johannes Schwenck, Kerstin Fuchs, Andreas Maurer, Christian la Fougere, Lars Zender, Bernd Pichler. In vivo imaging of tumor senescence with a novel beta-galactosidase specific PET tracer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-369.
Abstract 2593: AR-V7 and AR-V9 expression is not predictive of response to AR-axis targeting agents in metastatic castration-resistant prostate cancer
2018-07-01

Abstract In 2014, a landmark study was published demonstrating that androgen receptor splice variant (AR-V) AR-V7 expression was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumor cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR splice variants and treatment response. To further investigate, we designed a highly sensitive and specific whole blood assay for detecting AR-V7 and AR-V9. We then examined for a correlation between baseline AR-V7/V9 status and treatment outcome in 37 mCRPC patients commencing abiraterone or enzalutamide. Blood was taken in a PAXgene RNA tube at baseline prior to the commencement of therapy and at end of treatment (if applicable). 24% (9/37) of patients were AR-V-positive. Notably, PSA response rates did not significantly differ between AR-V-positive (6/9) and AR-V-negative (18/28) patients (66% vs. 64%, p=0.896). Likewise, median PSA progression-free survival was not significantly different between AR-V-positive and AR-V-negative patients (9.2 months vs. not reached; p=0.894). Additionally, we identified 2 patients who were AR-V7 negative at baseline but had converted to AR-V7 positive in their end-of-treatment sample. This was associated with much shorter PSA-PFS than those that remained negative (2.58 months vs. no reached), suggesting gain of AR-V expression may be a marker of acquired resistance. These data, which support the findings of the pivotal ARMOR3-SV clinical trial, suggest that baseline AR-V expression does not predict outcomes in mCRPC patients receiving abiraterone or enzalutamide. Citation Format: Sarah Q. To, Edmond Kwan, Heidi Fettke, Andrew Mant, Maria Docanto, Luciano Martelotto, Patricia Bukczynska, Nicole Ng, Lisa-Jane Graham, Phillip Parente, Carmel Pezaro, Kate Mahon, Lisa Horvath, Tilman Todenhöfer, Arun Azad. AR-V7 and AR-V9 expression is not predictive of response to AR-axis targeting agents in metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2593.
Abstract 846: Co-targeting of Axl and MerTK improves radiation response in HNSCC
2018-07-01

Abstract Axl and MerTK are members of the TAM family (Tyro, Axl and MerTK) of receptor tyrosine kinases and have been reported to be altered in several types of cancer including Head and Neck Squamous Carcinoma (HNSCC). It is well known that aberrant expression or activity of Axl is associated with resistance to various therapies. Therefore, the translational potential of targeting AXL in HNSCC is worthy, however poorly defined. We recently identified an adaptive feedback mechanism of resistance to AXL-targeting agents mediated by upregulation of MerTK that reveals a direct role for MerTK in resistance to Axl inhibition. In this study, we investigated potential radiosensitization by dual targeting of Axl and MerTK in combination with radiation in human HNSCC cell lines and xenografts (SCC47 and TU138). Immunoblot analysis demonstrated that endogenous levels of Axl or MerTK expression were distinct between these two cell lines. SCC47 cells expressed higher endogenous levels of Axl compared to Tu138. Tu138 expressed higher levels of MerTK compared to SCC47 cells. Radiation induced Axl phosphorylation in SCC47 cells but not in Tu138 cells in vitro. Next, inhibitors of Axl (R428) and/or MerTK (UNC2025) were utilized in combination with single dose radiation in vitro. Clonogenic assays showed that the Axl inhibitor alone acted as a potent radiosensitizer in SCC47 cells. To better define Axl's role in radiation response in HNSCC, we developed HN30-Vector and HN30-Axl stable cells and exposed them to radiation. Phosphorylation of Axl was increased 1 hour post-radiation in Axl overexpressed HN30 compared to parental HN30-Vector which expresses low endogenous levels of Axl. We also found that the HN30-Axl cell line was associated with radioresistance by clonogenic assays. Tumor xenograft studies demonstrated that the combination of R428 and UNC2025 inhibitors improved the efficacy of radiation in Tu138 but not in SCC47. Interestingly, radiation therapy alone was more effective in SCC47 tumors than TU138 tumors. These results reveal that the co-targeting of Axl and MerTK enhanced tumor growth delay in TU138 xenograft mouse models in vivo. Mechanisms of radiosensitization are currently under investigation. Citation Format: Mahyar Abbariki, Mahmoud Toulany, Mari Iida, Alecia Morgan, Kwang Nickel, Nellie McDaniel, Grace Kang, Chunrong Li, Paul Harari, Deric Wheeler. Co-targeting of Axl and MerTK improves radiation response in HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 846.
P3‐251: SERUM NEUROFILAMENT LIGHT CHAIN LEVELS ARE ASSOCIATED WITH CSF NEUROFILAMENT LIGHT CHAIN, COGNITIVE STATUS, AND DISEASE PROGRESSION IN AUTOSOMAL DOMINANT AD
2018-07-01

Measuring serum neurofilament light chain protein (NfL), a marker of neuronal injury, may provide a simple and minimally invasive assay to measure disease progression in neurodegenerative diseases, including Alzheimer disease (AD). This study examines cross-sectional and longitudinal associations between serum NfL levels and 1) CSF NfL levels, 2) cognitive status, and 3) disease progression. Individuals from the Dominantly Inherited Alzheimer's Network (DIAN) (asymptomatic mutation carriers (asMC), converters (Conv), or symptomatic mutation carriers (sMC) and asymptomatic familial mutation non-carriers (NC)) were studied (data freeze 11). Participants underwent 1-5 blood draws for cross-sectional and longitudinal NfL quantification and longitudinal cognitive assessments. A subset also underwent a lumbar puncture for baseline CSF NfL assessment. We used Pearson correlations to examine the cross-sectional relationship between serum NfL and CSF NfL in all subjects. Leveraging longitudinal data, we compared how the rate of change in serum NfL over time behaved as a function of baseline estimated year of dementia onset (EYO) between MCs and NCs. Next, we utilized t-tests based on the linear mixed effect model to compare longitudinal group differences between change in serum NfL over time and cognitive status. Cross-sectionally, higher serum NfL was positively associated with CSF NfL in the total cohort (r=0.798), and MCs (r=0.886). Longitudinally, change in serum NfL over time increased in MCs as a function of EYO with a peak approaching an EYO 0, and differed from NCs beginning at least a decade before anticipated symptoms. When comparing groups, sMC and Conv had higher rate of change in serum NfL values compared to NC and asMC (P's<0.001). These results suggest a strong relationship between serum and CSF NfL, bolstering the use of blood-based biomarkers for detecting CNS changes. Furthermore, change in serum NfL over time is associated with cognitive status, being highest in sMC, and can differentiate MC at NC groups at a relatively early EYO. Overall, cross-sectional and longitudinal serum NfL may be a viable biomarker of neurodegeneration and disease progression, allowing for a simple and accessible assay for evaluating neurodegeneration that should be considered as a potential outcome for clinical trials.
P4‐068: LEVELS OF THE ASTROCYTE‐DERIVED PROTEINS GFAP AND S100B IN THE CEREBROSPINAL FLUID OF HEALTHY INDIVIDUALS AND ALZHEIMER'S DISEASE PATIENTS AT DIFFERENT DISEASE STAGES
2018-07-01

The quantitative analysis of biomarker proteins in the cerebrospinal fluid (CSF) substantiates the clinical diagnosis of Alzheimer's disease (AD). However, when the disease becomes manifest, abeta- and tau-protein levels have already become static. Since it is believed that amyloid plaques are associated with activated astrocytes especially in early disease stages, we asked whether concentrations of the astrocyte-derived proteins glial fibrillary acidic protein (GFAP) and S100B in CSF might serve as markers of pathophysiological events especially in preclinical and early stages of AD. We used ELISA kits for the quantitative analysis of GFAP (IBL-International, Hamburg, Germany) and S100B (IBL). In healthy control subjects (n = 33), patients with subjective memory decline (SCD, n = 34), patients with mild cognitive impairment (MCI, n = 29) and AD patients (n = 20) from the DELCODE-cohort we quantified GFAP and S100B in CSF and compared mean levels between groups. Furthermore, we correlated levels of astroglial proteins in the CSF with standard biomarker concentrations (abeta42 and t-Tau). While there is a trend for a gradual increase of mean levels of both, GFAP and S100B in CSF from control to SCD, MCI and AD patients, we found that comparing the groups of AD patients and controls, GFAP and S100B levels in CSF are significantly higher in AD patients (p = 0.0164 and p = 0.0012 respectively). For GFAP, the CSF levels are also significantly higher in the MCI patients compared to controls (p = 0.0111). We determined low overall correlation coefficients when correlating concentrations of classical biomarker and astroglial markers. Correlations coefficients range from r = -0.247 for the correlation of GFAP and t-Tau in the MCI-cohort to r = 0.349 for the correlation of S100B and t-Tau in the control group. GFAP and S100B can reliably be detected in CSF. While we did not observe an increase in astroglial biomarkers in the groups of subjects at early disease stages, these markers might mirror neuropathological processes different from those underlying the biomarkers abeta42 and t-Tau. Long-term follow up studies will clarify whether GFAP and S100B might serve as markers for disease progression.