Identification of integrin drug targets for 17 solid tumor types.

Integrins are contributors to remodeling of the extracellular matrix and cell migration. Integrins participate in the assembly of the actin cytoskeleton, regulate growth factor signaling pathways, cell proliferation, and control cell motility. In solid tumors, integrins are involved in promoting metastasis to distant sites, and angiogenesis. Integrins are a key target in cancer therapy and imaging. Integrin antagonists have proven successful in halting invasion and migration of tumors. Overexpressed integrins are prime anti-cancer drug targets. To streamline the development of specific integrin cancer therapeutics, we curated data to predict which integrin heterodimers are pausible therapeutic targets against 17 different solid tumors. Computational analysis of The Cancer Genome Atlas (TCGA) gene expression data revealed a set of integrin targets that are differentially expressed in tumors. Filtered by FPKM (Fragments Per Kilobase of transcript per Million mapped reads) expression level, overexpressed subunits were paired into heterodimeric protein targets. By comparing the RNA-seq differential expression results with immunohistochemistry (IHC) data, overexpressed integrin subunits were validated. Biologics and small molecule drug compounds against these identified overexpressed subunits and heterodimeric receptors are potential therapeutics against these cancers. In addition, high-affinity and high-specificity ligands against these integrins can serve as efficient vehicles for delivery of cancer drugs, nanotherapeutics, or imaging probes against cancer

Online Pattern Matching for String Edit Distance with Moves

Edit distance with moves (EDM) is a string-to-string distance measure that includes substring moves in addition to ordinal editing operations to turn one string to the other. Although optimizing EDM is intractable, it has many applications especially in error detections. Edit sensitive parsing (ESP) is an efficient parsing algorithm that guarantees an upper bound of parsing discrepancies between different appearances of the same substrings in a string. ESP can be used for computing an approximate EDM as the L1 distance between characteristic vectors built by node labels in parsing trees. However, ESP is not applicable to a streaming text data where a whole text is unknown in advance. We present an online ESP (OESP) that enables an online pattern matching for EDM. OESP builds a parse tree for a streaming text and computes the L1 distance between characteristic vectors in an online manner. For the space-efficient computation of EDM, OESP directly encodes the parse tree into a succinct representation by leveraging the idea behind recent results of a dynamic succinct tree. We experimentally test OESP on the ability to compute EDM in an online manner on benchmark datasets, and we show OESP's efficiency.Comment: This paper has been accepted to the 21st edition of the International Symposium on String Processing and Information Retrieval (SPIRE2014

Status report on a natural laminar-flow nacelle flight experiment

The natural laminar flow (NLF) nacelle experiment is part of a drag reduction production program, and has the dual objectives of studying the extent of NLF on full scale nacelles in a flight environment and the effect of acoustic disturbance on the location of transition on the nacelle surface. The experiment is being conducted in two phases: (1) an NLF fairing was flown on a full scale Citation nacelle to develop the experiment technique and establish feasibility; (2) full scale, flow through, NLF nacelles located below the right wing of an experimental NASA OV-1 aircraft are evaluated. The measurements of most interest are the static pressure distribution and transition location on the nacelle surface, and the fluctuating pressure levels associated with the noise sources. Data are collected in combinations of acoustic frequencies and sound pressure levels. The results of phase 2 tests to date indicate that on shape GE2, natural laminar flow was maintained as far aft as the afterbody joint at 50 percent of the nacelle length. An aft facing step at this joint caused premature transition at this station. No change was observed in the transition pattern when the noise sources were operated

Autistic adults show preserved normalisation of sensory responses in gaze processing

Progress in our understanding of autism spectrum disorder (ASD) has recently been sought by characterising how systematic differences in canonical neural computations employed across the sensory cortex might contribute to clinical symptoms in diverse sensory, cognitive, and social domains. A key proposal is that ASD is characterised by reduced divisive normalisation of sensory responses. This provides a bridge between genetic and molecular evidence for an increased ratio of cortical excitation to inhibition in ASD and the functional characteristics of sensory coding that are relevant for understanding perception and behaviour. Here we tested this hypothesis in the context of gaze processing (i.e., the perception of other people's direction of gaze), a domain with direct relevance to the core diagnostic features of ASD. We show that reduced divisive normalisation in gaze processing is associated with specific predictions regarding the psychophysical effects of sensory adaptation to gaze direction, and test these predictions in adults with ASD. We report compelling evidence that both divisive normalisation and sensory adaptation occur robustly in adults with ASD in the context of gaze processing. These results have important theoretical implications for defining the types of divisive computations that are likely to be intact or compromised in this condition (e.g., relating to local vs distal control of cortical gain). These results are also a strong testament to the typical sensory coding of gaze direction in ASD, despite the atypical responses to others' gaze that are a hallmark feature of this diagnosis.This research was supported by a Wellcome Trust Senior Clinical Research Fellowship (100227) awarded to GR and Australian Research Council Discovery Project (DP160102239) awarded to CC. This work was enabled partly by a study visit grant to CP from the Experimental Psychology Society. We thank all the participants who gave up their time to take part in this research

Sampling time and performance in rat whisker sensory system

We designed a behavioural paradigm for vibro-tactile detection to characterise the sampling time and performance in the rat whisker sensory system. Rats initiated a trial by nose-poking into an aperture where their whiskers came into contact with two meshes. A continuous nose-poke for a random duration triggered stimulus presentation. Stimuli were a sequence of discrete Gaussian deflections of the mesh that increased in amplitude over time - across 5 conditions, time to maximum amplitude varied from 0.5 to 8 seconds. Rats indicated the detected stimulus by choosing between two reward spouts. Two rats completed more than 500 trials per condition. Rats' stimulus sampling duration increased and performance dropped with increasing task difficulty. For all conditions the median reaction time was longer for correct trials than incorrect trials. Higher rates of increment in stimulus amplitude resulted in faster rise in performance as a function of stimulus sampling duration. Rats' behaviour indicated a dynamic stimulus sampling whereby nose-poke was maintained until a stimulus was correctly identified or the rat experienced a false alarm. The perception was then manifested in behaviour after a motor delay. We thus modelled the results with 3 parameters: signal detection, false alarm, and motor delay. The model captured the main features of the data and produced parameter estimates that were biologically plausible and highly similar across the two rats

Population decoding in rat barrel cortex: optimizing the linear readout of correlated population responses

Sensory information is encoded in the response of neuronal populations. How might this information be decoded by downstream neurons? Here we analyzed the responses of simultaneously recorded barrel cortex neurons to sinusoidal vibrations of varying amplitudes preceded by three adapting stimuli of 0, 6 and 12 µm in amplitude. Using the framework of signal detection theory, we quantified the performance of a linear decoder which sums the responses of neurons after applying an optimum set of weights. Optimum weights were found by the analytical solution that maximized the average signal-to-noise ratio based on Fisher linear discriminant analysis. This provided a biologically plausible decoder that took into account the neuronal variability, covariability, and signal correlations. The optimal decoder achieved consistent improvement in discrimination performance over simple pooling. Decorrelating neuronal responses by trial shuffling revealed that, unlike pooling, the performance of the optimal decoder was minimally affected by noise correlation. In the non-adapted state, noise correlation enhanced the performance of the optimal decoder for some populations. Under adaptation, however, noise correlation always degraded the performance of the optimal decoder. Nonetheless, sensory adaptation improved the performance of the optimal decoder mainly by increasing signal correlation more than noise correlation. Adaptation induced little systematic change in the relative direction of signal and noise. Thus, a decoder which was optimized under the non-adapted state generalized well across states of adaptation

Infinite-dimensional Compact Quantum Semigroup

In this paper we construct a compact quantum semigroup structure on the Toeplitz algebra $\mathcal{T}$. The existence of a subalgebra, isomorphic to the algebra of regular Borel's measures on a circle with convolution product, in the dual algebra $\mathcal{T}^*$ is shown. The existence of Haar functionals in the dual algebra and in the above-mentioned subalgebra is proved. Also we show the connection between $\mathcal{T}$ and the structure of weak Hopf algebra.Comment: 17 page

Adaptation improves neural coding efficiency despite increasing correlations in variability

Exposure of cortical cells to sustained sensory stimuli results in changes in the neuronal response function. This phenomenon, known as adaptation, is a common feature across sensory modalities. Here, we quantified the functional effect of adaptation on the ensemble activity of cortical neurons in the rat whisker-barrel system. A multishank array of electrodes was used to allow simultaneous sampling of neuronal activity. We characterized the response of neurons to sinusoidal whisker vibrations of varying amplitude in three states of adaptation. The adaptors produced a systematic rightward shift in the neuronal response function. Consistently, mutual information revealed that peak discrimination performance was not aligned to the adaptor but to test amplitudes 3–9 um higher. Stimulus presentation reduced single neuron trial-to-trial response variability (captured by Fano factor) and correlations in the population response variability (noise correlation). We found that these two types of variability were inversely proportional to the average firing rate regardless of the adaptation state. Adaptation transferred the neuronal operating regime to lower rates with higher Fano factor and noise correlations. Noise correlations were positive and in the direction of signal, and thus detrimental to coding efficiency. Interestingly, across all population sizes, the net effect of adaptation was to increase the total information despite increasing the noise correlation between neurons.This work was supported by the Australian Research Council Discovery Project DP0987133 and the Australian National Health and Medical Research Council Project Grant 1028670

Gravitation on a Homogeneous Domain

Among all plastic deformations of the gravitational Lorentz vacuum \cite{wr1} a particular role is being played by conformal deformations. These are conveniently described by using the homogeneous space for the conformal group SU(2,2)/S(U(2)x U(2)) and its Shilov boundary - the compactified Minkowski space \tilde{M} [1]. In this paper we review the geometrical structure involved in such a description. In particular we demonstrate that coherent states on the homogeneous Kae}hler domain give rise to Einstein-like plastic conformal deformations when extended to \tilde{M} [2].Comment: 10 pages, 1 figure; four misprints in the original version corrected: one lacking closing parenthesis, two letters, and an overall sign in front of the primitive function on p.

Tailored stereotactic radiotherapy technique using deep inspiration breath-hold to reduce stomach dose for cardiac radioablation

PURPOSE: To provide a new insight on a novel safe cardiac radioablation using deep inspiration breath-hold (DIBH) to reduce gastrointestinal dose. MATERIALS AND METHODS: For treating incessant ventricular tachycardia (VT) originated from left ventricle inferior scar abutting the stomach, a target delineation and treatment planning for cardiac radioablation was performed. With four different computed tomography (CT) scan protocols-DIBH, full expiration breath-hold, four-dimensional (4D) CT without and with abdominal compression, the distances between the target and the stomach were compared. RESULTS: Among the protocols, the CT scan with DIBH showed largest distance between the target and the stomach and selected for the treatment planning. The prescribed dose was 25 Gy in a single fraction, and satisfactory dosimetric parameters were achieved with the DIBH. The patient was successfully treated with the DIBH, and experienced no acute toxicity. CONCLUSION: To gain the best benefit from cardiac radioablation, understanding the possible toxicity in the adjacent organs is crucial. By moving the heart with thoraco-diaphragmatic movement by DIBH, the target could be physically separated from the stomach