555 research outputs found
Scalable k-Means Clustering via Lightweight Coresets
Coresets are compact representations of data sets such that models trained on
a coreset are provably competitive with models trained on the full data set. As
such, they have been successfully used to scale up clustering models to massive
data sets. While existing approaches generally only allow for multiplicative
approximation errors, we propose a novel notion of lightweight coresets that
allows for both multiplicative and additive errors. We provide a single
algorithm to construct lightweight coresets for k-means clustering as well as
soft and hard Bregman clustering. The algorithm is substantially faster than
existing constructions, embarrassingly parallel, and the resulting coresets are
smaller. We further show that the proposed approach naturally generalizes to
statistical k-means clustering and that, compared to existing results, it can
be used to compute smaller summaries for empirical risk minimization. In
extensive experiments, we demonstrate that the proposed algorithm outperforms
existing data summarization strategies in practice.Comment: To appear in the 24th ACM SIGKDD International Conference on
Knowledge Discovery & Data Mining (KDD
A new approach to cultural scripts of trauma sequelae assessment: The sample case of Switzerland
Background
The novel concept of cultural scripts of trauma sequelae captures culture-specific expressions of posttraumatic distress (e.g., cognitive, emotional, interpersonal, psychosomatic changes) and their temporal associations. Cultural scripts of trauma sequelae complement pan-cultural (etic) diagnoses, such as posttraumatic stress disorder (PTSD) and Complex PTSD, as well as the cultural syndromes concept.
Objective
This study aimed to develop the cultural scripts of trauma inventory (CSTI) for German-speaking Switzerland and to explore temporal associations of script elements.
Method
Five semi-structured focus groups were conducted with psychotraumatologists (n = 8) and Swiss trauma survivors (n = 7). The interview schedule included open questions about different domains of potential posttraumatic changes (emotions, cognitions, worldviews, interpersonal relationships, body-related experiences, behavior, and growth). Data were analyzed using qualitative content analysis.
Results
The Swiss CSTI includes 57 emic elements that represent salient trauma sequelae (30 conformed with a theoretically derived item pool, 27 were newly phrased). Temporal script associations were visualized in a network, whereby self-deprecation, the urge to function and overcompensate, and the urge to hide and endure suffering had the highest number of connections.
Conclusion
While many posttraumatic changes identified in the present work seem to mirror pan-cultural phenomena represented in the Complex PTSD concept (e.g., self-deprecation), others (e.g., urge to function and perform, urge to hide and endure suffering) may be prominently related to Swiss culture with its value orientations. Knowledge about cultural scripts of trauma sequelae may provide a culture-specific framework that can help to understand individual experiences of distress and enable mental health practitioners to administer culturally sensitive interventions. Pending further validation, the Swiss CSTI bears the potential to advance culture-sensitive assessment of trauma sequelae
Verbundprojekt PARALOR: Parallele Algorithmen fĂŒr Routingprobleme im Flug- und StraĂenverkehr
Im Verbundprojekt PARALOR wird untersucht, wie parallele Algorithmen der kombinatorischen Optimierung zur Lösung groĂer Optimierungsprobleme aus der industriellen Praxis eingesetzt werden können. Dabei werden insbesondere konkrete Aufgabenstellungen aus dem Bereich der Flugplanoptimierung und der integrierten Steuerung von Fertigungslagern bearbeitet. Der Beitrag gibt einen Ăberblick ĂŒber die jeweiligen Problemstellungen, die verwendeten Algorithmen und die bisher erzielten Resultate. Insbesondere werden mit dem Parallelen Simulated Trading und dem Parallelen Branch-and-Bound parallele Methoden betrachtet, mit denen eine breite Klasse kombinatorischer Optimierungsprobleme behandelt werden kann
Induced point mutations in the phytoene synthase 1 gene cause differences in carotenoid content during tomato fruit ripening
In tomato, carotenoids are important with regard to major breeding traits such as fruit colour and human health. The enzyme phytoene synthase (PSY1) directs metabolic flux towards carotenoid synthesis. Through TILLING (Targeting Induced Local Lesions IN Genomes), we have identified two point mutations in the Psy1 gene. The first mutation is a knockout allele (W180*) and the second mutation leads to an amino acid substitution (P192L). Plants carrying the Psy1 knockout allele show fruit with a yellow flesh colour similar to the r, r mutant, with no further change in colour during ripening. In the line with P192L substitution, fruit remain yellow until 3Â days post-breaker and eventually turn red. Metabolite profiling verified the absence of carotenoids in the W180* line and thereby confirms that PSY1 is the only enzyme introducing substrate into the carotenoid pathway in ripening fruit. More subtle effects on carotenoid accumulation were observed in the P192L line with a delay in lycopene and ÎČ-carotene accumulation clearly linked to a very slow synthesis of phytoene. The observation of lutein degradation with ripening in both lines showed that lutein and its precursors are still synthesised in ripening fruit. Gene expression analysis of key genes involved in carotenoid biosynthesis revealed that expression levels of genes in the pathway are not feedback-regulated by low levels or absence of carotenoid compounds. Furthermore, protein secondary structure modelling indicated that the P192L mutation affects PSY1 activity through misfolding, leading to the low phytoene accumulation
Integrin-interleukin-4 mechanotransduction pathways in human chondrocytes
INTRODUCTION Low intensity ultrasound (LIUS) is a special type of sonic pressure that can generate radiation forces, shear stresses and cavitation MATERIALS AND METHODS C-28/I2 cells (human chondrocyte cell line) were cultured in monolayer and treated with LIUS at an intensity of 200 mW/cm 2 using Noblelife TM (Duplogen Inc., Suwon, Korea). The role of stretchactivated channels (SAC) and integrins was first examined in mediating the LIUS effects on the expression of type II collagen and aggrecan by RT-PCR and Western blot analysis. Inhibitors for SACs (gadolinium) and integrins (GRGDSP peptide or anti-integrin α1 antibody) were used to confirm their specificity. The involvement of three MPAKs signal pathways in the LIUS-mediated phenotypic changes of chondrocytes and its mechanotrnsduction pathways was also investigated using the phospho-specific antibodies. Similar approaches are currently undergoing using rabbit primary chondrocytes in three-dimensional alginate culture. RESULTS Effect of LIUS on the expression of cartilage matrix proteins C-28/I2 cells were stimulated with LIUS, and the optimal conditions for incubation and treatment times were examined in terms of type II collagen and aggrecan expression by RT-PCR. The mRNA level of type II collagen was the highest after 3 hr and that of aggrecan was gradually increasing by time, when cells were treated with LIUS for 15 min. Role of SACs in the LIUS signal When examined at 1, 3 and 6 hr after stimulation by RT-PCR, the LIUS effects on the mRNA levels of type II collagen and aggrecan were reduced by gadolinium treatment depending on time Role of integrins in the LIUS signal C-28/I2 cells were pre-incubated with the inhibitor (GRGDSP) or a control peptide (GRADSP) for 10 min before LIUS treatment. The mRNA levels of type II collagen and aggrecan were clearly induced by LIUS in the presence of GRADSP but were lower than the untreated control (0 hr) when GRGDSP was co-treated. MAPKs as downstream mediators of LIUS signal The phosphorylation of ERK and JNK was induced by LIUS but that of p38 kinase was not CONCLUSION These results suggest that the LIUS signal might be mediated via canonical mechanoreceptors of SACs and integrins and subsequently through JNK and ERK pathways. Further studies are necessary to understand more details of the LIUS signaling network and regulation mechanisms. In addition, our ongoing studies in a 3-D culture of chondrocytes would give more important information about the cellular and molecular mechanism(s) of LIUS effects on development of chondrogenic phenotypes. REFERENCES 1. Feril, L.B. Jr. and Kondo, T. Biological effects of low intensity ultrasound: the mechanism involved and its implications on therapy and on biosafety of ultrasound
Synchronization of developmental, molecular and metabolic aspects of sourceâsink interactions
Plants have evolved a multitude of strategies to adjust their growth according to external and internal signals. Interconnected metabolic and phytohormonal signalling networks allow adaption to changing environmental and developmental conditions and ensure the survival of species in fluctuating environments. In agricultural ecosystems, many of these adaptive responses are not required or may even limit crop yield, as they prevent plants from realizing their fullest potential. By lifting source and sink activities to their maximum, massive yield increases can be foreseen, potentially closing the future yield gap resulting from an increasing world population and the transition to a carbon-neutral economy. To do so, a better understanding of the interplay between metabolic and developmental processes is required. In the past, these processes have been tackled independently from each other, but coordinated efforts are required to understand the fine mechanics of sourceâsink relations and thus optimize crop yield. Here, we describe approaches to design high-yielding crop plants utilizing strategies derived from current metabolic concepts and our understanding of the molecular processes determining sink development.Research in the authorsâ laboratories was supported by the following grants: the cassava sourceâsink (CASS) project of the Bill and Melinda Gates Foundation (to A.R.F., H.E.N., M.S. and U.S.); the ERA-CAPs project SourSi (to A.R.F. and L.J.S.); the BIO2015-3019-EXP grant from the Spanish Ministry of Economy, Industry and Competitiveness and the PCIN-2017-032 CONCERT-JAPAN project financed by the Ministry of Science, Innovation and Universities (to S.P.); Australian Research Council DP180103834 (to Y.L.R.); the US National Science Foundation (grant no. IOS-1457183); the Agriculture and Food Research Initiative (AFRI; grant no. 2017-67013-26158) from the USDA National Institute of Food and Agriculture (to M.T.); the Finnish Centre of Excellence in Molecular Biology of Primary Producers (Academy of Finland CoE program 2014â2019; grant no. 271832); the Gatsby Foundation (grant no. GAT3395/PR3); the University of Helsinki (grant no. 799992091); the European Research Council Advanced Investigator Grant SYMDEV (grant no. 323052; to Y.H.); the BMBF (grant no. 031B0191); the DFG (SPP1530: WA3639/1-2, 2-1); and the Max-Planck-Society (to V.W.). We additionally thank D. Ko and R. Ruonala for their comments on the manuscript
Deterministic approach to microscopic three-phase traffic theory
Two different deterministic microscopic traffic flow models, which are in the
context of the Kerner's there-phase traffic theory, are introduced. In an
acceleration time delay model (ATD-model), different time delays in driver
acceleration associated with driver behaviour in various local driving
situations are explicitly incorporated into the model. Vehicle acceleration
depends on local traffic situation, i.e., whether a driver is within the free
flow, or synchronized flow, or else wide moving jam traffic phase. In a speed
adaptation model (SA-model), vehicle speed adaptation occurs in synchronized
flow depending on driving conditions. It is found that the ATD- and SA-models
show spatiotemporal congested traffic patterns that are adequate with empirical
results. In the ATD- and SA-models, the onset of congestion in free flow at a
freeway bottleneck is associated with a first-order phase transition from free
flow to synchronized flow; moving jams emerge spontaneously in synchronized
flow only. Differences between the ATD- and SA-models are studied. A comparison
of the ATD- and SA-models with stochastic models in the context of three phase
traffic theory is made. A critical discussion of earlier traffic flow theories
and models based on the fundamental diagram approach is presented.Comment: 40 pages, 14 figure
A remote secondary binding pocket promotes heteromultivalent targeting of DC-SIGN
Dendritic cells (DC) are antigen-presenting cells coordinating the interplay of the innate and the adaptive immune response. The endocytic C-type lectin receptors DC-SIGN and Langerin display expression profiles restricted to distinct DC subtypes and have emerged as prime targets for next-generation immunotherapies and anti-infectives. Using heteromultivalent liposomes copresenting mannosides bearing aromatic aglycones with natural glycan ligands, we serendipitously discovered striking cooperativity effects for DC-SIGN+ but not for Langerin+ cell lines. Mechanistic investigations combining NMR spectroscopy with molecular docking and molecular dynamics simulations led to the identification of a secondary binding pocket for the glycomimetics. This pocket, located remotely of DC-SIGNâs carbohydrate bindings site, can be leveraged by heteromultivalent avidity enhancement. We further present preliminary evidence that the aglycone allosterically activates glycan recognition and thereby contributes to DC-SIGN-specific cell targeting. Our findings have important implications for both translational and basic glycoscience, showcasing heteromultivalent targeting of DCs to improve specificity and supporting potential allosteric regulation of DC-SIGN and CLRs in general
Semiâinsulating nature of gas source molecular beam epitaxial InGaP grown at very low temperatures
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