Neurobiological systems for lexical representation and analysis in English.

Current research suggests that language comprehension engages two joint but functionally distinguishable neurobiological processes: a distributed bilateral system, which supports general perceptual and interpretative processes underpinning speech comprehension, and a left hemisphere (LH) frontotemporal system, selectively tuned to the processing of combinatorial grammatical sequences, such as regularly inflected verbs in English [Marslen-Wilson, W. D., & Tyler, L. K. Morphology, language and the brain: The decompositional substrate for language comprehension. Philosophical Transactions of the Royal Society: Biological Sciences, 362, 823-836, 2007]. Here we investigated how English derivationally complex words engage these systems, asking whether they selectively activate the LH system in the same way as inflections or whether they primarily engage the bilateral system that support nondecompositional access. In an fMRI study, we saw no evidence for selective activation of the LH frontotemporal system, even for highly transparent forms like bravely. Instead, a combination of univariate and multivariate analyses revealed the engagement of a distributed bilateral system, modulated by factors of perceptual complexity and semantic transparency. We discuss the implications for theories of the processing and representation of English derivational morphology and highlight the importance of neurobiological constraints in understanding these processes

Formation and Interaction of Membrane Tubes

We show that the formation of membrane tubes (or membrane tethers), which is a crucial step in many biological processes, is highly non-trivial and involves first order shape transitions. The force exerted by an emerging tube is a non-monotonic function of its length. We point out that tubes attract each other, which eventually leads to their coalescence. We also show that detached tubes behave like semiflexible filaments with a rather short persistence length. We suggest that these properties play an important role in the formation and structure of tubular organelles.Comment: 4 pages, 3 figure

Qualitative Multi-Objective Reachability for Ordered Branching MDPs

We study qualitative multi-objective reachability problems for Ordered Branching Markov Decision Processes (OBMDPs), or equivalently context-free MDPs, building on prior results for single-target reachability on Branching Markov Decision Processes (BMDPs). We provide two separate algorithms for "almost-sure" and "limit-sure" multi-target reachability for OBMDPs. Specifically, given an OBMDP, $\mathcal{A}$, given a starting non-terminal, and given a set of target non-terminals $K$ of size $k = |K|$, our first algorithm decides whether the supremum probability, of generating a tree that contains every target non-terminal in set $K$, is $1$. Our second algorithm decides whether there is a strategy for the player to almost-surely (with probability $1$) generate a tree that contains every target non-terminal in set $K$. The two separate algorithms are needed: we show that indeed, in this context, "almost-sure" $\not=$ "limit-sure" for multi-target reachability, meaning that there are OBMDPs for which the player may not have any strategy to achieve probability exactly $1$ of reaching all targets in set $K$ in the same generated tree, but may have a sequence of strategies that achieve probability arbitrarily close to $1$. Both algorithms run in time $2^{O(k)} \cdot |\mathcal{A}|^{O(1)}$, where $|\mathcal{A}|$ is the total bit encoding length of the given OBMDP, $\mathcal{A}$. Hence they run in polynomial time when $k$ is fixed, and are fixed-parameter tractable with respect to $k$. Moreover, we show that even the qualitative almost-sure (and limit-sure) multi-target reachability decision problem is in general NP-hard, when the size $k$ of the set $K$ of target non-terminals is not fixed.Comment: 47 page

Palladium(II) complexes of quinolinylaminophosphonates: synthesis, structural characterization, antitumor and antimicrobial activity

Three types of palladium(II) halide complexes of quinolinylaminophosphonates have been synthesized and studied. Diethyl and dibutyl [alpha-anilino-(quinolin-2-ylmethyl)]phosphonates (L1, 12) act as N,N-chelate ligands through the quinoline and aniline nitrogens giving complexes cis-[Pd(L1/12)X-2] (X Cl, Br) (1-4). Their 3-substituted analogues [alpha-anilino-(quinolin-3-ylmethyl)]phosphonates (L3, L4) form dihalidopalladium complexes trans-[Pd(L3/L4)(2)X-2] (5-8), with trans N-bonded ligand molecules only through the quinoline nitrogen. Dialkyl [alpha-(quinolin-3-ylamino)-N-benzyl]phosphonates (L5, L6) give tetrahalidodipalladium complexes [Pd-2(L5/L6)(3)X-4] (9-12), containing one bridging and two terminal ligand molecules. The bridging molecule is bonded to the both palladium atoms, one through the quinoline and the other through the aminoquinoline nitrogen, whereas terminal ligand molecules are coordinated each only to one palladium via the quinoline nitrogen. Each palladium ion is also bonded to two halide ions in a trans square-planar fashion. The new complexes were identified and characterized by elemental analyses and by IR, UV-visible, H-1, C-13 and P-31 nuclear magnetic resonance and ESI-mass spectroscopic studies. The crystal structures of complexes 1-4 and 6 were determined by X-ray structure analysis. The antitumor activity of complexes in vitro was investigated on several human tumor cell lines and the highest activity with cell growth inhibitory effects in the low micromolar range was observed for dipalladium complexes 11 and 12 derived from dibutyl ester L6. The antimicrobial properties in vitro of ligands and their complexes were studied using a wide spectrum of bacterial and fungal strains. No specific activity was noted. Only ligands L3 and L4 and tetrahalidodipalladium complexes 9 and 11 show poor activities against some Gram positive bacteria

Accumulation of driver and passenger mutations during tumor progression

Major efforts to sequence cancer genomes are now occurring throughout the world. Though the emerging data from these studies are illuminating, their reconciliation with epidemiologic and clinical observations poses a major challenge. In the current study, we provide a novel mathematical model that begins to address this challenge. We model tumors as a discrete time branching process that starts with a single driver mutation and proceeds as each new driver mutation leads to a slightly increased rate of clonal expansion. Using the model, we observe tremendous variation in the rate of tumor development - providing an understanding of the heterogeneity in tumor sizes and development times that have been observed by epidemiologists and clinicians. Furthermore, the model provides a simple formula for the number of driver mutations as a function of the total number of mutations in the tumor. Finally, when applied to recent experimental data, the model allows us to calculate, for the first time, the actual selective advantage provided by typical somatic mutations in human tumors in situ. This selective advantage is surprisingly small, 0.005 +- 0.0005, and has major implications for experimental cancer research

Incorporating kidney disease measures into cardiovascular risk prediction: Development and validation in 9 million adults from 72 datasets

Background: Chronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. CKD Patch is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures.Methods: Utilizing data from 4,143,535 adults from 35 datasets, we developed several CKD Patches incorporating eGFR and albuminuria, to enhance prediction of risk of atherosclerotic CVD (ASCVD) by the Pooled Cohort Equation (PCE) and CVD mortality by Systematic COronary Risk Evaluation (SCORE). The risk enhancement by CKD Patch was determined by the deviation between individual CKD measures and the values expected from their traditional CVD risk factors and the hazard ratios for eGFR and albuminuria. We then validated this approach among 4,932,824 adults from 37 independent datasets, comparing the original PCE and SCORE equations (recalibrated in each dataset) to those with addition of CKD Patch.Findings: We confirmed the prediction improvement with the CKD Patch for CVD mortality beyond SCORE and ASCVD beyond PCE in validation datasets (Δc-statistic 0.027 [95% CI 0.018-0.036] and 0.010 [0.007-0.013] and categorical net reclassification improvement 0.080 [0.032-0.127] and 0.056 [0.044-0.067], respectively). The median (IQI) of the ratio of predicted risk for CVD mortality with CKD Patch vs. the original prediction with SCORE was 2.64 (1.89-3.40) in very high-risk CKD (e.g., eGFR 30-44 ml/min/1.73m2 with albuminuria ≥30 mg/g), 1.86 (1.48-2.44) in high-risk CKD (e.g., eGFR 45-59 ml/min/1.73m2 with albuminuria 30-299 mg/g), and 1.37 (1.14-1.69) in moderate risk CKD (e.g., eGFR 60-89 ml/min/1.73m2 with albuminuria 30-299 mg/g), indicating considerable risk underestimation in CKD with SCORE. The corresponding estimates for ASCVD with PCE were 1.55 (1.37-1.81), 1.24 (1.10-1.54), and 1.21 (0.98-1.46).Interpretation: The CKD Patch can be used to quantitatively enhance ASCVD and CVD mortality risk prediction equations recommended in major US and European guidelines according to CKD measures, when available.Funding: US National Kidney Foundation and the NIDDK

High levels of effective long-distance dispersal may blur ecotypic divergence in a rare terrestrial orchid

Background: Gene flow and adaptive divergence are key aspects of metapopulation dynamics and ecological speciation. Long-distance dispersal is hard to detect and few studies estimate dispersal in combination with adaptive divergence. The aim of this study was to investigate effective long-distance dispersal and adaptive divergence in the fen orchid (Liparis loeselii (L.) Rich.). We used amplified fragment length polymorphism (AFLP)-based assignment tests to quantify effective long-distance dispersal at two different regions in Northwest Europe. In addition, genomic divergence between fen orchid populations occupying two distinguishable habitats, wet dune slacks and alkaline fens, was investigated by a genome scan approach at different spatial scales (continental, landscape and regional) and based on 451 AFLP loci. Results: We expected that different habitats would contribute to strong divergence and restricted gene flow resulting in isolation-by-adaptation. Instead, we found remarkably high levels of effective long-distance seed dispersal and low levels of adaptive divergence. At least 15% of the assigned individuals likely originated from among-population dispersal events with dispersal distances up to 220 km. Six (1.3%) ‘outlier’ loci, potentially reflecting local adaptation to habitat-type, were identified with high statistical support. Of these, only one (0.22%) was a replicated outlier in multiple independent dune-fen population comparisons and thus possibly reflecting truly parallel divergence. Signals of adaptation in response to habitat type were most evident at the scale of individual populations. Conclusions: The findings of this study suggest that the homogenizing effect of effective long-distance seed dispersal may overwhelm divergent selection associated to habitat type in fen orchids in Northwest Europe

Early decomposition in visual word recognition: Dissociating morphology, form, and meaning

The role of morphological, semantic, and form-based factors in the early stages of visual word recognition was investigated across different SOAs in a masked priming paradigm, focusing on English derivational morphology. In a first set of experiments, stimulus pairs co-varying in morphological decomposability and in semantic and orthographic relatedness were presented at three SOAs (36, 48, and 72 ms). No effects of orthographic relatedness were found at any SOA. Semantic relatedness did not interact with effects of morphological decomposability, which came through strongly at all SOAs, even for pseudo-suffixed pairs such as archer-arch. Derivational morphological effects in masked priming seem to be primarily driven by morphological decomposability at an early stage of visual word recognition, and are independent of semantic factors. A second experiment reversed the order of prime and target (stem-derived rather than derived-stem), and again found that morphological priming did not interact with semantic relatedness. This points to an early segmentation process that is driven by morphological decomposability and not by the structure or content of central lexical representations