On local linearization of control systems

We consider the problem of topological linearization of smooth (C infinity or real analytic) control systems, i.e. of their local equivalence to a linear controllable system via point-wise transformations on the state and the control (static feedback transformations) that are topological but not necessarily differentiable. We prove that local topological linearization implies local smooth linearization, at generic points. At arbitrary points, it implies local conjugation to a linear system via a homeomorphism that induces a smooth diffeomorphism on the state variables, and, except at "strongly" singular points, this homeomorphism can be chosen to be a smooth mapping (the inverse map needs not be smooth). Deciding whether the same is true at "strongly" singular points is tantamount to solve an intriguing open question in differential topology

Symbolic Logic meets Machine Learning: A Brief Survey in Infinite Domains

The tension between deduction and induction is perhaps the most fundamental issue in areas such as philosophy, cognition and artificial intelligence (AI). The deduction camp concerns itself with questions about the expressiveness of formal languages for capturing knowledge about the world, together with proof systems for reasoning from such knowledge bases. The learning camp attempts to generalize from examples about partial descriptions about the world. In AI, historically, these camps have loosely divided the development of the field, but advances in cross-over areas such as statistical relational learning, neuro-symbolic systems, and high-level control have illustrated that the dichotomy is not very constructive, and perhaps even ill-formed. In this article, we survey work that provides further evidence for the connections between logic and learning. Our narrative is structured in terms of three strands: logic versus learning, machine learning for logic, and logic for machine learning, but naturally, there is considerable overlap. We place an emphasis on the following "sore" point: there is a common misconception that logic is for discrete properties, whereas probability theory and machine learning, more generally, is for continuous properties. We report on results that challenge this view on the limitations of logic, and expose the role that logic can play for learning in infinite domains

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Prevalence of obsessive-compulsive disorder in Iran

BACKGROUND: Estimates of the annual prevalence for Obsessive Compulsive Disorder (OCD) were consistent across the international sites range, 1.9% – 2.5%. The nine population surveys, which used Diagnostic Interview Schedule, estimated a six-month prevalence of OCD ranging from 0.7% to 2.1%. This study performed in order to determine the prevalence of OCD in a population-based study among Iranian adults aged 18 and older and to study the association of them with factors such as sex, marital status, education, type of occupation and residential area. METHODS: A cross-sectional nationwide epidemiological study of the Iranian population aged 18 and older was designed to estimate the prevalence of psychiatric disorders and their association with the above mentioned factors. 25180 individuals were selected and interviewed through a randomized systematic and cluster sampling method from all Iranian households. Schedule for Affective Disorders and Schizophrenia (SADS) and Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria were used in diagnosis of OCD. 250 clinical psychologists interviewed the selected subjects face to face at their homes. RESULTS: The prevalence of OCD in Iran is 1.8% (0.7% and 2.8% in males and females; respectively). 50.3% of the survey sample were men, 49.9% women, 29.1% single, 67.45% married, 0.4% separated or divorced, 2.5% widow/widower and 4% undetermined. All of the above-mentioned factors were examined in the univariate and multivariate logistic regression models. Although the data did not fit the models well, but in univariate models, sex, the category "single" of marital status, age, the categories "business" and "housewife" and residential areas showed significant effect adjusting for the factors, but the models didn't fit the data properly. CONCLUSION: The study suggests that the prevalence of OCD is not rare in the community of Iran and is within the range of other countries. Similar to prior studies in other communities, OCD is more common in females than males

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells

<p>Abstract</p> <p>Background</p> <p>A major problem with the use of current chemotherapy regimens for several cancers, including breast cancer, is development of intrinsic or acquired drug resistance, which results in disease recurrence and metastasis. However, the mechanisms underlying this drug resistance are unknown. To study the molecular mechanisms underlying the invasive and metastatic activities of drug-resistant cancer cells, we generated a doxorubicin-resistant MCF-7 breast cancer cell line (MCF-7/DOX).</p> <p>Methods</p> <p>We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, DNA fragmentation assays, Western blot analysis, cell invasion assays, small interfering RNA (siRNA) transfection, reverse transcription-polymerase chain reaction, experimental lung metastasis models, and gelatin and fibrinogen/plasminogen zymography to study the molecular mechanism of metastatic activities in MCF-7/DOX cells.</p> <p>Results</p> <p>We found that MCF-7/DOX acquired invasive activities. In addition, Western blot analysis showed increased expression of epidermal growth factor receptor (EGFR) and Cox-2 in MCF-7/DOX cells. Inhibition of Cox-2, phosphoinositide 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase (MAPK) pathways effectively inhibited the invasive activities of MCF-7/DOX cells. Gelatin and fibrinogen/plasminogen zymography analysis showed that the enzymatic activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator were markedly higher in MCF-7/DOX cells than in the MCF-7 cells. <it>In vitro </it>invasion assays and mouse models of lung metastasis demonstrated that MCF-7/DOX cells acquired invasive abilities. Using siRNAs and agonists specific for prostaglandin E (EP) receptors, we found that EP1 and EP3 played important roles in the invasiveness of MCF-7/DOX cells.</p> <p>Conclusions</p> <p>We found that the invasive activity of MCF-7/DOX cells is mediated by Cox-2, which is induced by the EGFR-activated PI3K/Akt and MAPK pathways. In addition, EP1 and EP3 are important in the Cox-2-induced invasion of MCF-7/DOX cells. Therefore, not only Cox-2 but also EP1 and EP3 could be important targets for chemosensitization and inhibition of metastasis in breast cancers that are resistant to chemotherapy.</p

Nanoparticles for Local Drug Delivery to the Oral Mucosa: Proof of Principle Studies

Purpose To determine if solid lipid nanoparticles represent a viable strategy for local delivery of poorly water soluble and unstable chemopreventive compounds to human oral tissues. Methods Nanoparticle uptake and compound retention evaluations employed monolayer-cultured human oral squamous cell carcinoma (OSCC) cell lines and normal human oral mucosal explants. Feasibility of nanoparticle delivery was also evaluated with respect to the presence of phase-III efflux transporters in normal oral mucosal tissue and OSCC tissues. Results Functional uptake assays confirmed significantly greater internalization of nanoparticle-delivered fluorescent probe relative to free-fluorescent probe delivery, while concurrently demonstrating nanoparticle uptake rate differences among the OSCC cell lines and the phagocytic control human monocyte cell line. Mucosal explants exhibited nanoparticle penetration and internalization in the spinous and basal epithelial layer

New convolutions for quadratic-phase Fourier integral operators and their applications

We obtain new convolutions for quadratic-phase Fourier integral operators (which include, as subcases, e.g., the fractional Fourier transform and the linear canonical transform). The structure of these convolutions is based on properties of the mentioned integral operators and takes profit of weight-functions associated with some amplitude and Gaussian functions. Therefore, the fundamental properties of that quadratic-phase Fourier integral operators are also studied (including a Riemann-Lebesgue type lemma, invertibility results, a Plancherel type theorem and a Parseval type identity). As applications, we obtain new Young type inequalities, the asymptotic behaviour of some oscillatory integrals, and the solvability of convolution integral equations