julilili42/papers huggingface dataset:
Abstract 360: Senescent hepatocytes secrete CCL2 to accelerate liver cancer growth via accumulation of immunosuppressive myeloid cells
2015-08-01

Abstract Aim: Oncogene-induced senescence causes hepatocytes to secrete cytokines, which induce the immune-mediated clearance of these senescent cells, preventing malignant transformation and tumor initiation; a process termed ‘senescence surveillance’. However, senescent hepatocytes can give rise to hepatocellular carcinomas (HCC), if additional oncogenic mutations, e.g. p53 mutation, abrogate the senescence program. We set out to investigate the effect of senescent cell secreted cytokines on growth of neighboring liver tumor cells. Experimental procedure: To induce senescence in mouse livers, we hydrodynamically injected a transposon system, which encodes for either oncogenic Nras (NrasG12V) or an effector loop mutant (NrasG12V/D38A) that is incapable of signaling to downstream pathways, into C57BL/6 or CCR2-/- mice. To achieve tumor development in senescent livers, hepatocellular carcinoma cells were intrasplenically injected into mice, which expressed either NrasG12V or NrasG12V/D38A in the liver. Hepatic immune cell infiltrates were analyzed using flow cytometry and immunohistochemistry. Immunosuppressive ability of CD11b+Gr1+ myeloid cells was analyzed in vitro after fluorescence-activated cell sorting. Furthermore, peritumor tissue of 226 HCC patients was hierarchical clustered based on the expression of 35 senescence-associated genes. Senescence-associated gene signature was then compared with CCL2 expression and survival. Results: Senescent hepatocytes promoted growth of hepatocellular carcinoma cells through accumulation of immunosuppressive CD11b+Gr1+ myeloid cells. CD11b+Gr1+ cells inhibited T cell proliferation via an iNOS-dependent mechanism. Immunosuppressive myeloid cell accumulation as well as tumor growth promotion was abrogated, when senescence was induced in livers of CCR2 knockout mice, indicating a pivotal role for CCL2 in creating a tumor promoting immune environment. Finally, gene expression analysis in patients with hepatocellular carcinoma confirmed the association of senescence-induced CCL2 expression in peritumor tissue and poor prognosis. Conclusion: Senescent hepatocytes not only induce an inflammatory response that leads to their own clearance, preventing tumor initiation, but surprisingly also induce the accumulation of immunosuppressive myeloid cells that promote growth of neighboring hepatocellular carcinomas. Citation Format: Tobias Eggert, Juling Ji, Lars Zender, Xin Wei Wang, Tim F. Greten. Senescent hepatocytes secrete CCL2 to accelerate liver cancer growth via accumulation of immunosuppressive myeloid cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 360. doi:10.1158/1538-7445.AM2015-360
Abstract 1437: The activity of plasma membrane V-ATPases is critical for the invasion of breast cancer cells
2015-08-01

Abstract The V-ATPases are a family of ATP-driven proton pumps that have been implicated in breast cancer cell invasion. V-ATPases are found both intracellularly and on the plasma membrane of specialized acid-secreted cells and invasive cancer cells. As available inhibitors of the V-ATPase are membrane-permeable, it has not yet been examined whether intracellular or plasma membrane pumps are critical for invasiveness. It has been proposed that V-ATPases promote invasiveness by localizing to the plasma membrane. To test this hypothesis, we utilized two approaches to specifically inhibit the V-ATPases at the plasma membrane. First, we stably transfected invasive MB231 breast cancer cells with a V5-tagged construct of the membrane-embedded subunit c. This allows for extracellular expression of the V5 epitope. We then found that addition of an anti-V5 antibody specifically inhibited plasma membrane V-ATPase activity as well as in vitro invasion and migration of MB231 cells. Second, we utilized a biotin-conjugated form of the specific V-ATPase inhibitor bafilomycin to inhibit plasma membrane pumps. When bound to streptavidin, this compound is membrane impermeable. Addition of streptavidin-bound biotin-bafilomycin also inhibited in vitro invasion and migration of MB231 cells. These studies suggest that V-ATPases at the plasma membrane play a critical role in breast cancer cell invasion. We hypothesize that plasma membrane V-ATPases participate in invasion by creating an acidic microenvironment that promotes the activity of pH-dependent proteases. Overall, these results have significant implications for targeting the pump to prevent breast cancer metastasis. Citation Format: Kristina Cotter, Joseph Capecci, Souad Sennoune, Markus Huss, Martin Maier, Raul Martinez-Zaguilan, Michael Forgac. The activity of plasma membrane V-ATPases is critical for the invasion of breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1437. doi:10.1158/1538-7445.AM2015-1437
Is breathing rate a confounding variable in brain-computer interfaces (BCIs) based on EEG spectral power?
2015-08-01

Brain-computer interfaces (BCIs) enable paralyzed patients to interact with the world by directly decoding brain activity. We investigated if systematic changes in breathing rate affect EEG bandpower features that are commonly used in BCIs. This is of particular interest for the development of cognitive BCIs for patients with artificial ventilation, e.g. for those in late stages of amyotrophic lateral sclerosis (ALS). If subjects can alter the spectrum of the EEG by changing their breathing rate, decoding results obtained with healthy subjects may not generalize to this patient population. We recorded a high-density EEG from twelve healthy subjects, who were instructed to alternate between fast and slow breathing. We do not find any statistically significant modulation of EEG bandpower. As such, changes in breathing rate are unlikely to substantially bias the performance of BCIs based on EEG bandpower features.
Abstract 1924: Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes
2015-08-01

Abstract Distinct subtypes of triple negative (TN) breast cancer have currently been identified by tumor expression profiling and are thought to be influenced by the tumor microenvironment. However, little is known about the relationship between distinguishing histopathologic features of TN tumors, which reflect aspects of both tumor behavior and tumor microenvironment, and molecular TN subtypes. We analyzed whole genome expression profiles of 593 TN tumors from the Triple Negative Breast Cancer Consortium (TNBCC) using the Illumina Whole Genome DASL array. Histopathologic review of mitotic index, grade, trabecular pattern, growth pattern, involution, presence of ductal carcinoma in situ, and degree of lymphoid infiltrate, necrosis, fibrosis, and lobulitis was completed for 310 of these tumors. Clusters were identified both agnostically and using genes associated with these histopathologic features, and subtypes were evaluated for enriched pathways and associations with histopathologic features. Agnostic clustering identified four stable clusters which represented a basal-like (BL) signature, a luminal signature with overexpression of androgen receptor and targets, an immune signature, and a stromal (STR) signature. Overall, the TN tumors tended to have little or no necrosis (91%), high grade (88%), a high mitotic index (80%), fibrosis (77%), an epicentric growth pattern (62%), incomplete lobular involution (55%), trabecular structures (37%), lymphocytic infiltration (25%), adjacent ductal carcinoma in situ (24%), and variable amounts of lobulitis. Using a combined total of 2,776 unique probes individually associated with the ten histopathologic features measured, we identified six distinct TN subtypes, with an additional BL and STR signature compared to the four agnostic subtypes. Our findings suggest that histopathologic features that reflect heterogeneity in tumor cell structure and behavior as well as the tumor microenvironment, particularly the presence of lymphocytic infiltrate, are critical for TN subtype identification. Further work is needed to validate these signatures and to better understand the immunologic pathways associated with each subtype. Citation Format: Kristen Purrington, Daniel Visscher, Drakoulis Yannoukakos, Jane Carpenter, Heli Nevanlinna, Arto Mannerma, Xianshu Wang, Graham Giles, Wei Zheng, Angela Cox, Hiltrud Brauch, Ute Hamann, Diana Eccles, Celine M. Vachon, Fergus J. Couch. Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1924. doi:10.1158/1538-7445.AM2015-1924
Triggering Comet-Like Activity of Main Belt Comets
2015-08-01

Abstract Main Belt Comets (MBCs) have attracted a great deal of interest since their identification as a new class of bodies by Hsieh and Jewitt in 2006. Much of this interest is due to the implication that MBC activity is driven by the sublimation of volatile material (presumed to be water-ice) presenting these bodies as probable candidates for the delivery of a significant fraction of Earth's water. Results of the studies of the dynamics of MBCs suggest that these objects might have formed in-situ as the remnants of the break-up of large icy asteroids. Simulations also show that collisions among MBCs and small objects could have played an important role in triggering the cometary activity of these bodies. Such collisions might have exposed sub-surface water-ice which sublimated and created thin atmospheres and tails around MBCs. In order to drive the effort of understanding the nature of the activation of MBCs, we have investigated these collision processes by simulating the impacts in detail using a smooth particle hydrodynamics (SPH) approach that includes material strength and fracture models. We have carried out simulations for a range of impact velocities and angles, allowing m-sized impactors to erode enough of an MBC's surface to expose volatiles and trigger its activation. Impact velocities were varied between 0.5 km/s and 5.3 km/s, and the projectile radius was chosen to be 1 m. As expected, we observe significantly different crater depths depending on the impact energy, impact angle, and MBC's material strength. Results show that for all values of impact velocity and angle, crater depths are only a few meters, implying that if the activity of MBCs is due to the sublimation of water-ice, ice has to exist in no deeper than a few meters from the surface. We present details of our simulations and discuss the implications of their results.
Abstract 1311: The frequency of circulating Vδ1-positive but not Vδ2-positive γ/δ T cells correlates negatively with survival in late-stage melanoma and may be increased by ipilimumab treatment
2015-08-01

Abstract Recently, there has been a resurgence of interest in the possibility of using γ/δ-T cells in cancer immunotherapy, because these cells can kill melanoma cells in vitro, and IL-2 and zoledronate treatment can expand some human γδ cells in vitro and in animal models in vivo. The presence of the main subsets of γ/δ-T cells in late-stage melanoma patients and relationship with survival has not been extensively explored, although relatively lower percentages of Vδ2-positive cells has been reported in melanoma. Here, we present preliminary data on associations between the major γ/δ-T cell subsets and survival in melanoma patients, and whether baseline data are informative for predicting responses to ipilimumab treatment. We used a carefully validated set of monoclonal antibodies to assess γ/δ-phenotypes, because we found that certain commercial reagents were not behaving as specified (Wistuba-Hamprecht et al. OMIP-020: phenotypic characterization of human γδ T-cells by multicolor flow cytometry. Cytometry A. 2014; 85:522-4). Comparing a total of 39 stage IV melanoma patients with 27 controls, we found no overall differences in Vδ1 or Vδ2 T-cell frequencies, or in proportions of naïe (CD27, CD28-double positive, CD45RA+)-vs -late-differentiated (CD27,CD28-double negative, CD45RA+) γ/δ cells. However, Kaplan-Meier plots stratifying individual patients into groups with Vδ1 or Vδ2 frequencies above or below the median showed that the presence of Vδ1 but not Vδ2 cells negatively correlated with longer survival (p = 0.033 log-rank; p = 0.047 Breslow). In a subgroup of 9 patients, ipilimumab treatment resulted in an increase of peripheral Vδ1+ T-cells (p = 0.0391, Wilcoxon) but not of Vδ2+ T-cells (p = 0.375, Wilcoxon). We are currently analyzing data from a larger prospective study of ipilimumba treatment with over 100 patients, to confirm or refute these results. Citation Format: Kilian Wistuba-Hamprecht, Benjamin Weide, Alexander Martens, Graham P. Pawelec. The frequency of circulating Vδ1-positive but not Vδ2-positive γ/δ T cells correlates negatively with survival in late-stage melanoma and may be increased by ipilimumab treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1311. doi:10.1158/1538-7445.AM2015-1311
Pion light-front wave function, parton distribution and the electromagnetic form factor
2015-08-03

We derive the lowest-order valence light-front wave function for the pion with Lz=0 and |Lz|=1, which reproduces its valence parton distribution and the electromagnetic form factor consistent with data.
Text–Picture Integration: How Delayed Testing Moderates Recognition of Pictorial Information in Multimedia Learning
2015-08-03

Summary When learning with multimedia, text and pictures are assumed to be integrated with each other. Arndt, Schüler, and Scheiter (Learning &amp; Instruction, 35, 62–72, 2015) confirmed the process of text picture integration for sentence recognition, not, however, for picture recognition. The current paper investigates the underlying reasons for the latter finding. Two experiments are reported, where subjects memorized text–picture stimuli that differed in the specificity of information contained in either sentences or pictures. In a subsequent picture recognition test, subjects showed no integration effect after a 30‐minute delay (Experiments 1 and 2), but only after a 1‐week delay (Experiment 2). Furthermore, eye‐tracking data showed that participants sufficiently processed the pictures during learning (Experiment 1). This data pattern speaks in favor of the assumption that after a short delay participants had available a short‐lived pictorial surface representation, which masked the integration effect for pictorial recognition.Copyright © 2015 John Wiley &amp; Sons, Ltd.
Constructing meaning for up and down situated sentences: Is a sentence more than the sum of its words?
2015-08-03

abstract The present study was concerned with the question whether comprehension is based on mental simulation processes beyond the word level. In Experiment 1, participants were presented with coherent sentence pairs, consisting of a context sentence and a target sentence. Target sentences ended with a word referring to an entity with a typical location in the upper vertical space (e.g., bird in There she sees a bird ). Context sentences either supported the target entity’s typical location or not ( Anna looks to the sky vs. Anna looks to the ground , respectively). Participants responded to the final word of the sentence pair by pressing an up- or a down-key. The results showed a main effect of response direction (faster up compared to down responses) as well as an interaction between context location and response direction. In Experiment 2, participants were presented with incoherent sentence pairs with the same context sentences and different target sentences (whereby the target word was kept identical), but in an incoherent manner (target sentence: On the poster one sees a bird ). Here, the results showed a main effect of response direction but no interaction. The same result was obtained in Experiment 3, in which participants were presented with word pairs consisting of an up- or down-context word (e.g., sky vs. ground ) and an up-target word (e.g., bird ). Overall, the results provide evidence for the view that comprehension involves simulation processes at the word level as well as simulation processes at the sentence or discourse level.
Quantum stabilization of cosmic strings
2015-08-03

In the standard model, stabilization of a classically unstable cosmic string may occur through the quantum fluctuations of a heavy fermion doublet. We review numerical results from a semiclassical expansion in a reduced version of the standard model. In this expansion, the leading quantum corrections emerge at one loop level for many internal degrees of freedom. The resulting vacuum polarization energy and the binding energies of occupied fermion energy levels are of the same order, and must therefore be treated on equal footing. Populating these bound states lowers the total energy compared to the same number of free fermions and assigns a charge to the string. Charged strings are already stabilized for a fermion mass only somewhat larger than the top quark mass. Though obtained in a reduced version, these results suggest that neither extraordinarily large fermion masses nor unrealistic couplings are required to bind a cosmic string in the standard model. Furthermore, we also review results for a quantum stabilization mechanism that prevents closed Nielsen–Olesen-type strings from collapsing.
Individual Organ Failure and Concomitant Risk of Mortality Differs According to the Type of Admission to ICU – A Retrospective Study of SOFA Score of 23,795 Patients
2015-08-04

The dynamic evolution of OD/OF within 72h after ICU admission and mortality differed between patients depending on their types of admission. This has to be considered to exclude a systematic bias during multi-center trials.
Perception of temporal asymmetries in dynamic facial expressions
2015-08-04

In the current study we examined whether timeline-reversals and emotional direction of dynamic facial expressions affect subjective experience of human observers. We recorded natural movies of faces that increased or decreased their expressions of fear, and played them either in the natural frame order or reversed from last to first frame (reversed timeline). This led to four conditions of increasing or decreasing fear, either following the natural or reversed temporal trajectory of facial dynamics. This 2-by-2 factorial design controlled for visual low-level properties, static visual content, and motion energy across the different factors. It allowed us to examine perceptual consequences that would occur if the timeline trajectory of facial muscle movements during the increase of an emotion are not the exact mirror of the timeline during the decrease. It additionally allowed us to study perceptual differences between increasing and decreasing emotional expressions. Perception of these time-dependent asymmetries have not yet been quantified. We found that three emotional measures, emotional intensity, artificialness of facial movement, and convincingness or plausibility of emotion portrayal, were affected by timeline-reversals as well as by the emotional direction of the facial expressions. Our results imply that natural dynamic facial expressions contain temporal asymmetries, and show that deviations from the natural timeline lead to a reduction of perceived emotional intensity and convincingness, and to an increase of perceived artificialness of the dynamic facial expression. In addition, they show that decreasing facial expressions are judged as less plausible than increasing facial expressions. Our findings are of relevance for both, behavioral as well as neuroimaging studies, as processing and perception are influenced by temporal asymmetries.
KEPLER 453 b—THE 10thKEPLERTRANSITING CIRCUMBINARY PLANET
2015-08-05

We present the discovery of Kepler-453 b, a 6.2 planet in a low-eccentricity, 240.5 day orbit about an eclipsing binary. The binary itself consists of a 0.94 and 0.195 pair of stars with an orbital period of 27.32 days. The plane of the planet's orbit is rapidly precessing, and its inclination only becomes sufficiently aligned with the primary star in the latter portion of the Kepler data. Thus three transits are present in the second half of the light curve, but none of the three conjunctions that occurred during the first half of the light curve produced observable transits. The precession period is ~103 years, and during that cycle, transits are visible only ~8.9% of the time. This has the important implication that for every system like Kepler-453 that we detect, there are ~11.5 circumbinary systems that exist but are not currently exhibiting transits. The planet's mass is too small to noticeably perturb the binary, and consequently its mass is not measurable with these data; however, our photodynamical model places a 1σ upper limit of . With a period 8.8 times that of the binary, the planet is well outside the dynamical instability zone. It does, however, lie within the habitable zone of the binary, making it the third of 10 Keplercircumbinary planets to do so.
Meta-Analysis of Arabidopsis KANADI1 Direct Target Genes Identifies a Basic Growth-Promoting Module Acting Upstream of Hormonal Signaling Pathways
2015-08-05

An intricate network of antagonistically acting transcription factors mediates the formation of a flat leaf lamina of Arabidopsis (Arabidopsis thaliana) plants. In this context, members of the class III homeodomain leucine zipper (HD-ZIPIII) transcription factor family specify the adaxial domain (future upper side) of the leaf, while antagonistically acting KANADI transcription factors determine the abaxial domain (future lower side). Here, we used a messenger RNA sequencing approach to identify genes regulated by KANADI1 (KAN1) and subsequently performed a meta-analysis combining our data sets with published genome-wide data sets. Our analysis revealed that KAN1 acts upstream of several genes encoding auxin biosynthetic enzymes. When exposed to shade, we found three YUCCA genes, YUC2, YUC5, and YUC8, to be transcriptionally up-regulated, which correlates with an increase in the levels of free auxin. When ectopically expressed, KAN1 is able to transcriptionally repress these three YUC genes and thereby block shade-induced auxin biosynthesis. Consequently, KAN1 is able to strongly suppress shade-avoidance responses. Taken together, we hypothesize that HD-ZIPIII/KAN form the basis of a basic growth-promoting module. Hypocotyl extension in the shade and outgrowth of new leaves both involve auxin synthesis and signaling, which are under the direct control of HD-ZIPIII/KAN.