Development of an aptamer-based biosensing system for measuring luteinizing hormone pulsatility for infertility treatment

Poster Presentation - Theme 1: Cell biologyNormal fertility in human involves a highly orchestrated signal communication between the hypothalamic-pituitary-gonadal. The pulsatile release of Luteinizing Hormone (LH) from pituitary gland is the key element in this ”concerto” for the simulation of sex steroid hormones synthesis and the production of mature eggs. Specific alterations in LH pulsatile pattern are linked to hypothalamic dysfunction in female patient with anovulatory infertility - by knowing the information of this pattern, clinicians can decide whether the patient needs treatment with pituitary hormones. However, there is currently no ...postprin

Beyond Correlation Filters: Learning Continuous Convolution Operators for Visual Tracking

Discriminative Correlation Filters (DCF) have demonstrated excellent performance for visual object tracking. The key to their success is the ability to efficiently exploit available negative data by including all shifted versions of a training sample. However, the underlying DCF formulation is restricted to single-resolution feature maps, significantly limiting its potential. In this paper, we go beyond the conventional DCF framework and introduce a novel formulation for training continuous convolution filters. We employ an implicit interpolation model to pose the learning problem in the continuous spatial domain. Our proposed formulation enables efficient integration of multi-resolution deep feature maps, leading to superior results on three object tracking benchmarks: OTB-2015 (+5.1% in mean OP), Temple-Color (+4.6% in mean OP), and VOT2015 (20% relative reduction in failure rate). Additionally, our approach is capable of sub-pixel localization, crucial for the task of accurate feature point tracking. We also demonstrate the effectiveness of our learning formulation in extensive feature point tracking experiments. Code and supplementary material are available at http://www.cvl.isy.liu.se/research/objrec/visualtracking/conttrack/index.html.Comment: Accepted at ECCV 201

Oligonucleotide Functionalised Microbeads: Indispensable Tools for High-Throughput Aptamer Selection

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Harmonic Analysis of Boolean Networks: Determinative Power and Perturbations

Consider a large Boolean network with a feed forward structure. Given a probability distribution on the inputs, can one find, possibly small, collections of input nodes that determine the states of most other nodes in the network? To answer this question, a notion that quantifies the determinative power of an input over the states of the nodes in the network is needed. We argue that the mutual information (MI) between a given subset of the inputs X = {X_1, ..., X_n} of some node i and its associated function f_i(X) quantifies the determinative power of this set of inputs over node i. We compare the determinative power of a set of inputs to the sensitivity to perturbations to these inputs, and find that, maybe surprisingly, an input that has large sensitivity to perturbations does not necessarily have large determinative power. However, for unate functions, which play an important role in genetic regulatory networks, we find a direct relation between MI and sensitivity to perturbations. As an application of our results, we analyze the large-scale regulatory network of Escherichia coli. We identify the most determinative nodes and show that a small subset of those reduces the overall uncertainty of the network state significantly. Furthermore, the network is found to be tolerant to perturbations of its inputs

Criticality in correlated quantum matter

At quantum critical points (QCP) \cite{Pfeuty:1971,Young:1975,Hertz:1976,Chakravarty:1989,Millis:1993,Chubukov:1 994,Coleman:2005} there are quantum fluctuations on all length scales, from microscopic to macroscopic lengths, which, remarkably, can be observed at finite temperatures, the regime to which all experiments are necessarily confined. A fundamental question is how high in temperature can the effects of quantum criticality persist? That is, can physical observables be described in terms of universal scaling functions originating from the QCPs? Here we answer these questions by examining exact solutions of models of correlated systems and find that the temperature can be surprisingly high. As a powerful illustration of quantum criticality, we predict that the zero temperature superfluid density, $\rho_{s}(0)$, and the transition temperature, $T_{c}$, of the cuprates are related by $T_{c}\propto\rho_{s}(0)^y$, where the exponent $y$ is different at the two edges of the superconducting dome, signifying the respective QCPs. This relationship can be tested in high quality crystals.Comment: Final accepted version not including minor stylistic correction

Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples

Measuring luteinising hormone pulsatility with a robotic aptamer-enabled electrochemical reader

Normal reproductive functioning is critically dependent on pulsatile secretion of luteinising hormone (LH). Assessment of LH pulsatility is important for the clinical diagnosis of reproductive disorders, but current methods are hampered by frequent blood sampling coupled to expensive serial immunochemical analysis. Here, we report the development and application of a Robotic APTamer-enabled Electrochemical Reader (RAPTER) electrochemical analysis system to determine LH pulsatility. Through selective evolution of ligands by exponential enrichment (SELEX), we identify DNA aptamers that bind specifically to LH and not to related hormones. The aptamers are integrated into electrochemical aptamer-based (E-AB) sensors on a robotic platform. E-AB enables rapid, sensitive and repeatable determination of LH concentration profiles. Bayesian Spectrum Analysis is applied to determine LH pulsatility in three distinct patient cohorts. This technology has the potential to transform the clinical care of patients with reproductive disorders and could be developed to allow real-time in vivo hormone monitoring

The optical counterpart to gamma-ray burst GRB970228 observed using the Hubble Space Telescope

Although more than 2,000 astronomical gamma-ray bursts (GRBs) have been detected, and numerous models proposed to explain their occurrence, they have remained enigmatic owing to the lack of an obvious counterpart at other wavelengths. The recent ground-based detection of a transient source in the vicinity of GRB 970228 may therefore have provided a breakthrough. The optical counterpart appears to be embedded in an extended source which, if a galaxy as has been suggested, would lend weight to those models that place GRBs at cosmological distances. Here we report the observations using the Hubble Space Telescope of the transient counterpart and extended source 26 and 39 days after the initial gamma-ray outburst. We find that the counterpart has faded since the initial detection (and continues to fade), but the extended source exhibits no significant change in brightness between the two dates of observations reported here. The size and apparent constancy between the two epochs of HST observations imply that it is extragalactic, but its faintness makes a definitive statement about its nature difficult. Nevertheless, the decay profile of the transient source is consistent with a popular impulsive-fireball model, which assumes a merger between two neutron stars in a distant galaxy.Comment: 11 pages + 2 figures. To appear in Nature (29 May 1997 issue

A new interpretation of total column BrO during Arctic spring

Emission of bromine from sea-salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO "hotspots" during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short-lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere. Copyright 2010 by the American Geophysical Union