685 research outputs found
ChIP-BIT: Bayesian inference of target genes using a novel joint probabilistic model of ChIP-seq profiles.
Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) has greatly improved the reliability with which transcription factor binding sites (TFBSs) can be identified from genome-wide profiling studies. Many computational tools are developed to detect binding events or peaks, however the robust detection of weak binding events remains a challenge for current peak calling tools. We have developed a novel Bayesian approach (ChIP-BIT) to reliably detect TFBSs and their target genes by jointly modeling binding signal intensities and binding locations of TFBSs. Specifically, a Gaussian mixture model is used to capture both binding and background signals in sample data. As a unique feature of ChIP-BIT, background signals are modeled by a local Gaussian distribution that is accurately estimated from the input data. Extensive simulation studies showed a significantly improved performance of ChIP-BIT in target gene prediction, particularly for detecting weak binding signals at gene promoter regions. We applied ChIP-BIT to find target genes from NOTCH3 and PBX1 ChIP-seq data acquired from MCF-7 breast cancer cells. TF knockdown experiments have initially validated about 30% of co-regulated target genes identified by ChIP-BIT as being differentially expressed in MCF-7 cells. Functional analysis on these genes further revealed the existence of crosstalk between Notch and Wnt signaling pathways
Direct generation of photon triplets using cascaded photon-pair sources
Non-classical states of light, such as entangled photon pairs and number
states, are essential for fundamental tests of quantum mechanics and optical
quantum technologies. The most widespread technique for creating these quantum
resources is the spontaneous parametric down-conversion (SPDC) of laser light
into photon pairs. Conservation of energy and momentum in this process, known
as phase-matching, gives rise to strong correlations which are used to produce
two-photon entanglement in various degrees of freedom. It has been a
longstanding goal of the quantum optics community to realise a source that can
produce analogous correlations in photon triplets, but of the many approaches
considered, none have been technically feasible. In this paper we report the
observation of photon triplets generated by cascaded down-conversion. Here each
triplet originates from a single pump photon, and therefore quantum
correlations will extend over all three photons in a way not achievable with
independently created photon pairs. We expect our photon-triplet source to open
up new avenues of quantum optics and become an important tool in quantum
technologies. Our source will allow experimental interrogation of novel quantum
correlations, the post-selection free generation of tripartite entanglement
without post- selection and the generation of heralded entangled-photon pairs
suitable for linear optical quantum computing. Two of the triplet photons have
a wavelength matched for optimal transmission in optical fibres, ideally suited
for three-party quantum communication. Furthermore, our results open
interesting regimes of non-linear optics, as we observe spontaneous
down-conversion pumped by single photons, an interaction also highly relevant
to optical quantum computing.Comment: 7 pages, 3 figures, 1 table; accepted by Natur
De Broglie Wavelength of a Nonlocal Four-Photon
Superposition is one of the most distinct features of quantum theory and has
been demonstrated in numerous realizations of Young's classical double-slit
interference experiment and its analogues. However, quantum entanglement - a
significant coherent superposition in multiparticle systems - yields phenomena
that are much richer and more interesting than anything that can be seen in a
one-particle system. Among them, one important type of multi-particle
experiments uses path-entangled number-states, which exhibit pure higher-order
interference and allow novel applications in metrology and imaging such as
quantum interferometry and spectroscopy with phase sensitivity at the
Heisenberg limit or quantum lithography beyond the classical diffraction limit.
Up to now, in optical implementations of such schemes lower-order interference
effects would always decrease the overall performance at higher particle
numbers. They have thus been limited to two photons. We overcome this
limitation and demonstrate a linear-optics-based four-photon interferometer.
Observation of a four-particle mode-entangled state is confirmed by
interference fringes with a periodicity of one quarter of the single-photon
wavelength. This scheme can readily be extended to arbitrary photon numbers and
thus represents an important step towards realizable applications with
entanglement-enhanced performance.Comment: 19 pages, 4 figures, submitted on November 18, 200
Clinical correlation of nonalcoholic fatty liver disease in a Chinese taxi drivers population in Taiwan: Experience at a teaching hospital
<p>Abstract</p> <p>Background</p> <p>To explore any gender-related differences in the prevalence of conditions-associated with non-alcoholic fatty liver disease (NAFLD) among Taiwanese taxi drivers in Taipei, Taiwan.</p> <p>Methods</p> <p>We studied 1635 healthy taxi drivers (1541 males and 94 females) who volunteered for physical check-ups in 2006. Blood samples and ultrasound fatty liver sonography results were collected.</p> <p>Results</p> <p>The prevalence of NAFLD was 66.4% and revealed no statistically significant decrease with increasing age (p = 0.58). Males exhibited a greater prevalence of NAFLD than did females (67.5% vs 47.9%, p < 0.0001). Gender-related differences for associated factors were found. For males, hypertension, hyperuricemia, higher AST, higher ALT, hypertriglyceridemia, and higher fasting plasma glucose were significantly related to NAFLD. These conditions were not sigfinicantly related to NAFLD in females.</p> <p>Conclusion</p> <p>Several gender-related differences were noted for NAFLD among Taiwanese taxi drivers.</p
On thermodynamic modeling and the role of the second law of thermodynamics in geophysics
The article contains a brief review of elements of thermodynamic modeling in theoretical geophysics. We motivate the existence of the second law of thermodynamics in macroscopic theoretical physics and demonstrate its evaluation. In particular we show its consequences in the construction of constitutive laws for a two-component poroelastic medium. This construction is also related to microstructural properties verified by means of the second law
Von Bezold assimilation effect reverses in stereoscopic conditions
Lightness contrast and lightness assimilation are opposite phenomena: in contrast,
grey targets appear darker when bordering bright surfaces (inducers) rather than dark ones; in
assimilation, the opposite occurs. The question is: which visual process favours the occurrence
of one phenomenon over the other? Researchers provided three answers to this question. The
first asserts that both phenomena are caused by peripheral processes; the second attributes their
occurrence to central processes; and the third claims that contrast involves central processes,
whilst assimilation involves peripheral ones. To test these hypotheses, an experiment on an IT
system equipped with goggles for stereo vision was run. Observers were asked to evaluate the
lightness of a grey target, and two variables were systematically manipulated: (i) the apparent
distance of the inducers; and (ii) brightness of the inducers. The retinal stimulation was kept
constant throughout, so that the peripheral processes remained the same. The results show that
the lightness of the target depends on both variables. As the retinal stimulation was kept constant, we
conclude that central mechanisms are involved in both lightness contrast and lightness assimilation
Constitutive TL1A (TNFSF15) Expression on Lymphoid or Myeloid Cells Leads to Mild Intestinal Inflammation and Fibrosis
TL1A is a member of the TNF superfamily and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, a subset of Crohn's disease (CD) patients with the risk TL1A haplotype is associated with elevated TL1A expression and a more severe disease course. To investigate the in vivo role of elevated TL1A expression, we generated two transgenic (Tg) murine models with constitutive Tl1a expression in either lymphoid or myeloid cells. Compared to wildtype (WT) mice, constitutive expression of Tl1a in either lymphoid or myeloid cells showed mild patchy inflammation in the small intestine, which was more prominent in the ileum. In addition, mice with constitutive Tl1a expression exhibited enhanced intestinal and colonic fibrosis compared to WT littermates. The percentage of T cells expressing the gut homing chemokine receptors CCR9 and CCR10 was higher in the Tl1a Tg mice compared to WT littermates. Sustained expression of Tl1A in T cells also lead to increased Foxp3+ Treg cells. T cells or antigen presenting cells (APC) with constitutive expression of Tl1a were found to have a more activated phenotype and mucosal mononuclear cells exhibit enhanced Th1 cytokine activity. These results indicated an important role of TL1A in mucosal T cells and APC function and showed that up-regulation of TL1A expression can promote mucosal inflammation and gut fibrosis
Intervention to enhance skilled arm and hand movements after stroke: A feasibility study using a new virtual reality system
<p>Abstract</p> <p>Background</p> <p>Rehabilitation programs designed to develop skill in upper extremity (UE) function after stroke require progressive practice that engage and challenge the learner. Virtual realty (VR) provides a unique environment where the presentation of stimuli can be controlled systematically for optimal challenge by adapting task difficulty as performance improves. We describe four VR tasks that were developed and tested to improve arm and hand movement skills for individuals with hemiparesis.</p> <p>Methods</p> <p>Two participants with chronic post-stroke paresis and different levels of motor severity attended 12 training sessions lasting 1 to 2 hours each over a 3-week period. Behavior measures and questionnaires were administered pre-, mid-, and post-training.</p> <p>Results</p> <p>Both participants improved VR task performance across sessions. The less impaired participant averaged more time on task, practiced a greater number of blocks per session, and progressed at a faster rate over sessions than the more impaired participant. Impairment level did not change but both participants improved functional ability after training. The less impaired participant increased the number of blocks moved on the Box & Blocks test while the more impaired participant achieved 4 more items on the Functional Test of the Hemiparetic UE.</p> <p>Conclusion</p> <p>Two participants with differing motor severity were able to engage in VR based practice and improve performance over 12 training sessions. We were able to successfully provide individualized, progressive practice based on each participant's level of movement ability and rate of performance improvement.</p
Long-term medical utilization following ventilator-associated pneumonia in acute stroke and traumatic brain injury patients: a case-control study
<p>Abstract</p> <p>Background</p> <p>The economic burden of ventilator-associated pneumonia (VAP) during the index hospitalization has been confirmed in previous studies. However, the long-term economic impact is still unclear. The aim of this study is to examine the effect of VAP on medical utilization in the long term.</p> <p>Methods</p> <p>This is a retrospective case-control study. Study subjects were patients experiencing their first traumatic brain injury, acute hemorrhagic stroke, or acute ischemic stroke during 2004. All subjects underwent endotracheal intubation in the emergency room (ER) on the day of admission or the day before admission, were transferred to the intensive care unit (ICU) and were mechanically ventilated for 48 hours or more. A total of 943 patients who developed VAP were included as the case group, and each was matched with two control patients without VAP by age ( ± 2 years), gender, diagnosis, date of admission ( ± 1 month) and hospital size, resulting in a total of 2,802 patients in the study. Using robust regression and Poisson regression models we examined the effect of VAP on medical utilization including hospitalization expenses, outpatient expenses, total medical expenses, number of ER visits, number of readmissions, number of hospitalization days and number of ICU days, during the index hospitalization and during the following 2-year period.</p> <p>Results</p> <p>Patients in the VAP group had higher hospitalization expenses, longer length of stay in hospital and in ICU, and a greater number of readmissions than the control group patients.</p> <p>Conclusions</p> <p>VAP has a significant impact on medical expenses and utilization, both during the index hospitalization during which VAP developed and in the longer term.</p
Down-regulation of SFRP1 as a putative tumor suppressor gene can contribute to human hepatocellular carcinoma
<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. SFRP1 (the secreted frizzled-related protein 1), a putative tumor suppressor gene mapped onto chromosome 8p12-p11.1, the frequent loss of heterozygosity (LOH) region in human HCC, encodes a Wingless-type (Wnt) signaling antagonist and is frequently inactivated by promoter methylation in many human cancers. However, whether the down-regulation of SFRP1 can contribute to hepatocarcinogenesis still remains unclear.</p> <p>Methods</p> <p>We investigated the expression of SFRP1 through real time RT-PCR and immunohistochemistry staining. The cell growth and colony formation were observed as the overexpression and knockdown of SFRP1. The DNA methylation status within SFRP1 promoter was analyzed through methylation-specific PCR or bisulphate-treated DNA sequencing assays. Loss of heterozygosity was here detected with microsatellite markers.</p> <p>Results</p> <p>SFRP1 was significantly down-regulated in 76.1% (35/46) HCC specimens at mRNA level and in 30% (30/100) HCCs indicated by immunohistochemistry staining, as compared to adjacent non-cancerous livers. The overexpression of SFRP1 can significantly inhibit the cell growth and colony formation of YY-8103, SMMC7721, and Hep3B cells. The RNA interference against the constitutional SFRP1 in the offspring SMMC7721 cells, which were stably transfected by ectopic SFRP1, can markedly promote cell growth of these cells. LOH of both microsatellite markers D8S532 and D8SAC016868 flanking the gene locus was found in 13% (6 of 46 HCCs) and 6.5% (3 of 46 HCCs) of the informative cases, respectively, where 5 of 8 HCC specimens with LOH showed the down-regulation of SFRP1. DNA hypermethylation within SFRP1 promoter was identified in two of three HCC specimens without SFRP1 expression. Moreover, the DNA methylation of SFRP1 promoter was significantly reduced, along with the re-expression of the gene, in those HCC cell lines, Bel7404, QGY7701, and MHCC-H, as treated by DAC.</p> <p>Conclusion</p> <p>Our data suggested that the down-regulation of SFRP1 as a candidate tumor suppressor gene, triggered by the epigenetic and/or genetic events, could contribute to the oncogenesis of HCC.</p
- …