The role of the metabotropic glutamate receptor 5 in nicotine addiction.

This review summarizes the evidence for the potential involvement of metabotropic glutamate receptor 5 (mGluR5) in the development of nicotine addiction. Nicotine is consumed worldwide and is highly addictive. Previous research has extensively investigated the role of dopamine in association with reward learning and addiction, which has provided strong evidence for the involvement of dopaminergic neuronal circuitry in nicotine addiction. More recently, researchers focused on glutamatergic transmission after nicotine abuse, and its involvement in the reinforcing and rewarding effects of nicotine addiction. A number of robust preclinical and clinical studies have shown mGluR5 signaling as a facilitating mechanism of nicotine addiction and nicotine withdrawal. Specifically, clinical studies have illustrated lower cortical mGluR5 density in smokers compared to non-smokers in the human brain. In addition, mGluR5 might selectively regulate craving and withdrawal. This suggests that mGluR5 could be a key receptor in the development of nicotine addiction and therefore clinical trials to examine the therapeutic potential of mGluR5 agents could help to contribute to reduce nicotine addiction in society

Quantification of Bound Microbubbles in Ultrasound Molecular Imaging

Molecular markers associated with diseases can be visualized and quantified noninvasively with targeted ultrasound contrast agent (t-UCA) consisting of microbubbles (MBs) that can bind to specific molecular targets. Techniques used for quantifying t-UCA assume that all unbound MBs are taken out of the blood pool few minutes after injection and only MBs bound to the molecular markers remain. However, differences in physiology, diseases, and experimental conditions can increase the longevity of unbound MBs. In such conditions, unbound MBs will falsely be quantified as bound MBs. We have developed a novel technique to distinguish and classify bound from unbound MBs. In the post-processing steps, first, tissue motion was compensated using block-matching (BM) techniques. To preserve only stationary contrast signals, a minimum intensity projection (MinIP) or 20th-percentile intensity projection (PerIP) was applied. The after-flash MinIP or PerIP was subtracted from the before-flash MinIP or PerIP. In this way, tissue artifacts in contrast images were suppressed. In the next step, bound MB candidates were detected. Finally, detected objects were tracked to classify the candidates as unbound or bound MBs based on their displacement. This technique was validated in vitro, followed by two in vivo experiments in mice. Tumors (n = 2) and salivary glands of hypercholesterolemic mice (n = 8) were imaged using a commercially available scanner. Boluses of 100 mu L of a commercially available t-UCA targeted to angiogenesis markers and untargeted control UCA were injected separately. Our results show considerable reduction in misclassification of unbound MBs as bound ones. Using our method, the ratio of bound MBs in salivary gland for images with targeted UCA versus control UCA was improved by up to two times compared with unprocessed images

On the pathogenesis of penile venous leakage: role of the tunica albuginea

<p>Abstract</p> <p>Background</p> <p>Etiology of venogenic erectile dysfunction is not exactly known. Various pathologic processes were accused but none proved entirely satisfactory. These include presence of large venous channels draining corpora cavernosa, Peyronie's disease, diabetes and structural alterations in fibroblastic components of trabeculae and cavernous smooth muscles. We investigated hypothesis that tunica albuginea atrophy with a resulting subluxation and redundancy effects venous leakage during erection.</p> <p>Methods</p> <p>18 patients (mean age 33.6 ± 2.8 SD years) with venogenic erectile dysfunction and 17 volunteers for control (mean age 31.7 ± 2.2 SD years) were studied. Intracorporal pressure was recorded in all subjects; tunica albuginea biopsies were taken from 18 patients and 9 controls and stained with hematoxylin and eosin and Masson's trichrome stains.</p> <p>Results</p> <p>In flaccid phase intracorporal pressure recorded a mean of 11.8 ± 0.8 cm H₂O for control subjects and for patients of 5.2 ± 0.6 cm, while during induced erection recorded 98.4 ± 6.2 and 5.9 ± 0.7 cmH₂O, respectively. Microscopically, tunica albuginea of controls consisted of circularly-oriented collagen impregnated with elastic fibers. Tunica albuginea of patients showed degenerative and atrophic changes of collagen fibers; elastic fibers were scarce or absent.</p> <p>Conclusion</p> <p>Study has shown that during erection intracorporal pressure of patients with venogenic erectile dysfunction was significantly lower than that of controls. Tunica albuginea collagen fibers exhibited degenerative and atrophic changes which presumably lead to tunica albuginea subluxation and floppiness. These tunica albuginea changes seem to explain cause of lowered intracorporal pressure which apparently results from loss of tunica albuginea veno-occlusive mechanism. Causes of tunica albuginea atrophic changes and subluxation need to be studied.</p

Nonlinear Markov Random Fields Learned via Backpropagation

Although convolutional neural networks (CNNs) currently dominate competitions on image segmentation, for neuroimaging analysis tasks, more classical generative approaches based on mixture models are still used in practice to parcellate brains. To bridge the gap between the two, in this paper we propose a marriage between a probabilistic generative model, which has been shown to be robust to variability among magnetic resonance (MR) images acquired via different imaging protocols, and a CNN. The link is in the prior distribution over the unknown tissue classes, which are classically modelled using a Markov random field. In this work we model the interactions among neighbouring pixels by a type of recurrent CNN, which can encode more complex spatial interactions. We validate our proposed model on publicly available MR data, from different centres, and show that it generalises across imaging protocols. This result demonstrates a successful and principled inclusion of a CNN in a generative model, which in turn could be adapted by any probabilistic generative approach for image segmentation.Comment: Accepted for the international conference on Information Processing in Medical Imaging (IPMI) 2019, camera ready versio

High-spin States in \u3csup\u3e191, 193\u3c/sup\u3eAu and \u3csup\u3e192\u3c/sup\u3ePt: Evidence for Oblate Deformation and Triaxial Shapes

High-spin states of 191, 193Au and 192Pt have been populated in the 186W(11B, xn) and 186W(11B, p4n) reactions, respectively, at a beam energy of 68 MeV and their γ decay was studied using the YRAST Ball detector array at the Wright Nuclear Structure Laboratory at Yale University. The level scheme of 193Au has been extended up to Iπ = 55/2+. New transitions were observed also in 191Au and 192Pt. Particle-plus-Triaxial-Rotor (PTR) and Total Routhian Surface (TRS) calculations were performed to determine the equilibrium deformations of the Au isotopes. The predictions for oblate deformations in these nuclei are in agreement with the experimental data. Development of nonaxial shapes is discussed within the framework of the PTR model

Triaxial Deformation and Nuclear Shape Transition in \u3csup\u3e192\u3c/sup\u3eAu

Background: Nuclei in the A≈190 mass region show gradual shape changes from prolate through nonaxial deformed shapes and ultimately towards spherical shapes as the Pb region is approached. Exploring how this shape evolution occurs will help us understand the evolution of collectivity in this region. Purpose: The level scheme of the 192Au nucleus in A ≈ 190 region was studied in order to deduce its deformations. Methods: High-spin states of 192Au have been populated in the 186W(11B, 5n) reaction at a beam energy of 68 MeV and their γ decay was studied using the YRAST Ball detector array at the Wright Nuclear Structure Laboratory (WNSL), Yale University. Results: Based on double and triple γ-ray coincidence data the level scheme of 192Au has been extended up to Iπ = 32+ at an excitation energy of ∼6 MeV. Conclusion: The results are discussed in the framework of pairing and deformation self-consistent total Routhian surface (TRS) and cranked shell model (CSM) calculations. The comparison of the experimental observations with the calculations indicates that this nucleus takes a nonaxial shape similar to other Au nuclei in this region

Self-consistent Spectral Function for Non-Degenerate Coulomb Systems and Analytic Scaling Behaviour

Novel results for the self-consistent single-particle spectral function and self-energy are presented for non-degenerate one-component Coulomb systems at various densities and temperatures. The GW^0-method for the dynamical self-energy is used to include many-particle correlations beyond the quasi-particle approximation. The self-energy is analysed over a broad range of densities and temperatures (n=10^17/cm^3-10^27/cm^3, T=10^2 eV/k_B-10^4 eV/k_B). The spectral function shows a systematic behaviour, which is determined by collective plasma modes at small wavenumbers and converges towards a quasi-particle resonance at higher wavenumbers. In the low density limit, the numerical results comply with an analytic scaling law that is presented for the first time. It predicts a power-law behaviour of the imaginary part of the self-energy, Im Sigma ~ -n^(1/4). This resolves a long time problem of the quasi-particle approximation which yields a finite self-energy at vanishing density.Comment: 28 pages, 9 figure

Leading-order QCD Analysis of Neutrino-Induced Dimuon Events

The results of a leading-order QCD analysis of neutrino-induced charm production are presented. They are based on a sample of 4111 \numu- and 871 \anumu-induced opposite-sign dimuon events with $E_{\mu 1},E_{\mu 2} > 6~{\rm GeV}$, $35 5.5\,{\rm GeV^2}$, observed in the CHARM~II detector exposed to the CERN wideband neutrino and antineutrino beams. The analysis yields the value of \linebreak the charm quark mass $m_c=1.79\pm0.38\,{\rm GeV}/c^2$ and the Cabibbo--Kobayashi--Maskawa matrix element $|V_{cd}|=0.219\pm0.016$. The strange quark content of the nucleon is found to be suppressed with respect to non-strange sea quarks by a factor $\kappa =0.39\pm0.09$

Mechanical model for a collagen fibril pair in extracellular matrix

In this paper, we model the mechanics of a collagen pair in the connective tissue extracellular matrix that exists in abundance throughout animals, including the human body. This connective tissue comprises repeated units of two main structures, namely collagens as well as axial, parallel and regular anionic glycosaminoglycan between collagens. The collagen fibril can be modeled by Hooke's law whereas anionic glycosaminoglycan behaves more like a rubber-band rod and as such can be better modeled by the worm-like chain model. While both computer simulations and continuum mechanics models have been investigated the behavior of this connective tissue typically, authors either assume a simple form of the molecular potential energy or entirely ignore the microscopic structure of the connective tissue. Here, we apply basic physical methodologies and simple applied mathematical modeling techniques to describe the collagen pair quantitatively. We find that the growth of fibrils is intimately related to the maximum length of the anionic glycosaminoglycan and the relative displacement of two adjacent fibrils, which in return is closely related to the effectiveness of anionic glycosaminoglycan in transmitting forces between fibrils. These reveal the importance of the anionic glycosaminoglycan in maintaining the structural shape of the connective tissue extracellular matrix and eventually the shape modulus of human tissues. We also find that some macroscopic properties, like the maximum molecular energy and the breaking fraction of the collagen, are also related to the microscopic characteristics of the anionic glycosaminoglycan