17,265 research outputs found
Generalizations of Tucker-Fan-Shashkin lemmas
Tucker and Ky Fan's lemma are combinatorial analogs of the Borsuk-Ulam
theorem (BUT). In 1996, Yu. A. Shashkin proved a version of Fan's lemma, which
is a combinatorial analog of the odd mapping theorem (OMT). We consider
generalizations of these lemmas for BUT-manifolds, i.e. for manifolds that
satisfy BUT. Proofs rely on a generalization of the OMT and on a lemma about
the doubling of manifolds with boundaries that are BUT-manifolds.Comment: 10 pages, 2 figure
A Novel Method for Epileptic Seizure Detection Using Coupled Hidden Markov Models
We propose a novel Coupled Hidden Markov Model to detect epileptic seizures
in multichannel electroencephalography (EEG) data. Our model defines a network
of seizure propagation paths to capture both the temporal and spatial evolution
of epileptic activity. To address the intractability introduced by the coupled
interactions, we derive a variational inference procedure to efficiently infer
the seizure evolution from spectral patterns in the EEG data. We validate our
model on EEG aquired under clinical conditions in the Epilepsy Monitoring Unit
of the Johns Hopkins Hospital. Using 5-fold cross validation, we demonstrate
that our model outperforms three baseline approaches which rely on a classical
detection framework. Our model also demonstrates the potential to localize
seizure onset zones in focal epilepsy.Comment: To appear in MICCAI 2018 Proceeding
The Global Boundary Stratotype Section and Point (GSSP) for the base of the Albian Stage, of the Cretaceous, the Col de Pré-Guittard section, Arnayon, Drôme, France
Following the unanimous approval of the Executive Committee on the International Union of Geological Sciences as notified on April 8, 2016, the Global boundary Stratotype Section and Point for the base of the Albian Stage of the Cretaceous is defined at the first occurrence datum of the planktonic foraminiferan Microhedbergella renilaevis Huber and Leckie, 2011 at a level 37.4 meters above the base of the Marnes Bleues Formation and 40 cm above the base of the Niveau Kilian marker bed in the section SSE of the Col de Pré-Guittard, Arnayon, Drôme, France. The first occurrence of Microhedbergella renilaevis is placed within a 100-m section of argillaceous sediments with 28 secondary markers including calcareous nannofossils, planktonic foraminifera, an inoceramid bivalve, ammonites, stable carbon isotopes, and local marker beds
Elucidating the Role of Topological Constraint on the Structure of Overstretched DNA Using Fluorescence Polarization Microscopy
The combination of DNA force spectroscopy and polarization microscopy of fluorescent DNA intercalator dyes can provide valuable insights into the structure of DNA under tension. These techniques have previously been used to characterize S-DNA—an elongated DNA conformation that forms when DNA overstretches at forces ≥ 65 pN. In this way, it was deduced that the base pairs of S-DNA are highly inclined, relative to those in relaxed (B-form) DNA. However, it is unclear whether and how topological constraints on the DNA may influence the base-pair inclinations under tension. Here, we apply polarization microscopy to investigate the impact of DNA pulling geometry, torsional constraint, and negative supercoiling on the orientations of intercalated dyes during overstretching. In contrast to earlier predictions, the pulling geometry (namely, whether the DNA molecule is stretched via opposite strands or the same strand) is found to have little influence. However, torsional constraint leads to a substantial reduction in intercalator tilting in overstretched DNA, particularly in AT-rich sequences. Surprisingly, the extent of intercalator tilting is similarly reduced when the DNA molecule is negatively supercoiled up to a critical supercoiling density (corresponding to ∼70% reduction in the linking number). We attribute these observations to the presence of P-DNA (an overwound DNA conformation). Our results suggest that intercalated DNA preferentially flanks regions of P-DNA rather than those of S-DNA and also substantiate previous suggestions that P-DNA forms predominantly in AT-rich sequences
Ascaroside Expression in Caenorhabditis elegans Is Strongly Dependent on Diet and Developmental Stage
Background:
The ascarosides form a family of small molecules that have been isolated from cultures of the nematode Caenorhabditis elegans. They are often referred to as “dauer pheromones” because most of them induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. Thus, ascarosides have multiple functions. Until now, it has been generally assumed that ascarosides are constitutively expressed during nematode development.
Methodology/Principal Findings:
Cultures of C. elegans were developmentally synchronized on controlled diets. Ascarosides released into the media, as well as stored internally, were quantified by LC/MS. We found that ascaroside biosynthesis and release were strongly dependent on developmental stage and diet. The male attracting pheromone was verified to be a blend of at least four ascarosides, and peak production of the two most potent mating pheromone components, ascr#3 and asc#8 immediately preceded or coincided with the temporal window for mating. The concentration of ascr#2 increased under starvation conditions and peaked during dauer formation, strongly supporting ascr#2 as the main population density signal (dauer pheromone). After dauer formation, ascaroside production largely ceased and dauer larvae did not release any ascarosides. These findings show that both total ascaroside production and the relative proportions of individual ascarosides strongly correlate with these compounds' stage-specific biological functions.
Conclusions/Significance:
Ascaroside expression changes with development and environmental conditions. This is consistent with multiple functions of these signaling molecules. Knowledge of such differential regulation will make it possible to associate ascaroside production to gene expression profiles (transcript, protein or enzyme activity) and help to determine genetic pathways that control ascaroside biosynthesis. In conjunction with findings from previous studies, our results show that the pheromone system of C. elegans mimics that of insects in many ways, suggesting that pheromone signaling in C. elegans may exhibit functional homology also at the sensory level. In addition, our results provide a strong foundation for future behavioral modeling studies
Long-term survival rates of laryngeal cancer patients treated by radiation and surgery, radiation alone, and surgery alone : studied by lognormal and Kaplan-Meier survival methods
BACKGROUND: Validation of the use of the lognormal model for predicting long-term survival rates using short-term follow-up data. METHODS: 907 cases of laryngeal cancer were treated from 1973–1977 by radiation and surgery (248), radiation alone (345), and surgery alone (314), in registries of Connecticut and Metropolitan Detroit of the SEER database, with known survival status up to 1999. Phase 1 of this study used the minimum chi-square test to assess the goodness of fit of the survival times of those who died with disease to a lognormal distribution. Phase 2 used the maximum likelihood method to estimate long-term survival rates using short-term follow-up data. In order to validate the lognormal model, the estimated long-term cancer-specific survival rates (CSSR) were compared with the values calculated by the Kaplan-Meier (KM) method using long-term data. RESULTS: The 25-year CSSR were predicted to be 72%, 68% and 65% for treatments by radiation and surgery, by radiation alone, and by surgery alone respectively, using short-term follow-up data by the lognormal model. Corresponding results calculated by the KM method were: 72+/-3%, 68+/-3% and 66+/-4% respectively. CONCLUSIONS: The lognormal model was validated for the prediction of the long-term survival rates of laryngeal cancer patients treated by these different methods. The lognormal model may become a useful tool in research on outcomes
Patient-derived tumour xenografts for breast cancer drug discovery
Despite remarkable advances in our understanding of the drivers of human malignancies, new targeted therapies often fail to show sufficient efficacy in clinical trials. Indeed, the cost of bringing a new agent to market has risen substantially in the last several decades, in part fuelled by extensive reliance on preclinical models that fail to accurately reflect tumour heterogeneity. To halt unsustainable rates of attrition in the drug discovery process, we must develop a new generation of preclinical models capable of reflecting the heterogeneity of varying degrees of complexity found in human cancers. Patient-derived tumour xenograft (PDTX) models prevail as arguably the most powerful in this regard because they capture cancer's heterogeneous nature. Herein, we review current breast cancer models and their use in the drug discovery process, before discussing best practices for developing a highly annotated cohort of PDTX models. We describe the importance of extensive multidimensional molecular and functional characterisation of models and combination drug-drug screens to identify complex biomarkers of drug resistance and response. We reflect on our own experiences and propose the use of a cost-effective intermediate pharmacogenomic platform (the PDTX-PDTC platform) for breast cancer drug and biomarker discovery. We discuss the limitations and unanswered questions of PDTX models; yet, still strongly envision that their use in basic and translational research will dramatically change our understanding of breast cancer biology and how to more effectively treat it.This work was supported by Cancer Research UK (grant number RG84936)
Glauber theory of initial- and final-state interactions in (p,2p) scattering
We develop the Glauber theory description of initial- and final-state
interactions (IFSI) in quasielastic A(p,2p) scattering. We study the
IFSI-distortion effects both for the inclusive and exclusive conditions. In
inclusive reaction the important new effect is an interaction between the two
sets of the trajectories which enter the calculation of IFSI-distorted one-body
density matrix for inclusive (p,2p) scattering and are connected with
incoherent elastic rescatterings of the initial and final protons on spectator
nucleons. We demonstrate that IFSI-distortions of the missing momentum
distribution are large over the whole range of missing momentum both for
inclusive and exclusive reactions and affect in a crucial way the
interpretation of the BNL data on (p,2p) scattering. Our numerical results show
that in the region of missing momentum p_{m}\lsim 100-150 MeV/c the
incoherent IFSI increase nuclear transparency by 5-10\%. The incoherent IFSI
become dominant at p_{m}\gsim 200 MeV/c.Comment: Accepted in Z. Phys.A, Latex, 26 pages, uuencoded 9 figure
The Underestimation Of Egocentric Distance: Evidence From Frontal Matching Tasks
There is controversy over the existence, nature, and cause of error in egocentric distance judgments. One proposal is that the systematic biases often found in explicit judgments of egocentric distance along the ground may be related to recently observed biases in the perceived declination of gaze (Durgin & Li, Attention, Perception, & Psychophysics, in press), To measure perceived egocentric distance nonverbally, observers in a field were asked to position themselves so that their distance from one of two experimenters was equal to the frontal distance between the experimenters. Observers placed themselves too far away, consistent with egocentric distance underestimation. A similar experiment was conducted with vertical frontal extents. Both experiments were replicated in panoramic virtual reality. Perceived egocentric distance was quantitatively consistent with angular bias in perceived gaze declination (1.5 gain). Finally, an exocentric distance-matching task was contrasted with a variant of the egocentric matching task. The egocentric matching data approximate a constant compression of perceived egocentric distance with a power function exponent of nearly 1; exocentric matches had an exponent of about 0.67. The divergent pattern between egocentric and exocentric matches suggests that they depend on different visual cues
- …