403 research outputs found

    Integrin-independent movement of immune cells

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    Cell motility requires the temporal and spatial coordination of the actin cytoskeleton with cell-matrix adhesions. Since their discovery more than 20 years ago, integrins have been at the center of cell-matrix adhesion research. Integrin-mediated adhesions link the actin network to the extracellular matrix and are commonly observed as cells migrate across rigid two-dimensional substrates. However, as more cell motility studies are being conducted in three-dimensional (3D) culture systems and in vivo, the role of integrins has become less clear. Recent work has shown that leukocyte migration in 3D contexts can be integrin-independent and that alternative mechanisms of cell adhesion are employed

    Waring's number for large subgroups of double-struck Z_p

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    Let p be a prime, Z_p be the finite field in p elements, k be a positive integer, and A be the multiplicative subgroup of nonzero k-th powers in Z_p. The goal of this paper is to determine, for a given positive integer s, a value t_s such that if |A| ≫ t_s then every element of Z_p is a sum of s k-th powers. We obtain t_4 = p^{\frac{22}{39} + \in}, t_5 = p^{\frac{15}{29} + \in} and for s s ≄ 6, t_s = p^{\frac{9s+45}{29s+33} + \in}. For s ≄ 24 further improvements are made, such as t_32 = p^{\frac{5}{16} + \in} and t_128 = p^{\frac{1}{4}}

    Active bacterial core surveillance of the emerging infections program network.

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    Active Bacterial Core surveillance (ABCs) is a collaboration between the Centers for Disease Control and Prevention and several state health departments and universities participating in the Emerging Infections Program Network. ABCs conducts population-based active surveillance, collects isolates, and performs studies of invasive disease caused by Streptococcus pneumoniae, group A and group B Streptococcus, Neisseria meningitidis, and Haemophilus influenzae for a population of 17 to 30 million. These pathogens caused an estimated 97,000 invasive cases, resulting in 10,000 deaths in the United States in 1998. Incidence rates of these pathogens are described. During 1998, 25% of invasive pneumococcal infections in ABCs areas were not susceptible to penicillin, and 13.3% were not susceptible to three classes of antibiotics. In 1998, early-onset group B streptococcal disease had declined by 65% over the previous 6 years. More information on ABCs is available at www.cdc.gov/ncidod/dbmd/abcs. ABCs specimens will soon be available to researchers through an archive

    Assessment and Revision of Clinical Pharmacy Practice Internet Websites

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    Background: Health care professionals, trainees, and patients use the Internet extensively. Editable Web sites may contain inaccurate, incomplete, and/or outdated information that may mislead the public’s perception of the topic. Objective: To evaluate the editable, online descriptions of clinical pharmacy and pharmacist and attempt to improve their accuracy. Methods: The authors identified key areas within clinical pharmacy to evaluate for accuracy and appropriateness on the Internet. Current descriptions that were reviewed on public domain Web sites included: (1) clinical pharmacy and the clinical pharmacist, (2) pharmacy education, (3) clinical pharmacy and development and provision for reimbursement, (4) clinical pharmacists and advanced specialty certifications/training opportunities, (5) pharmacists and advocacy, and (6) clinical pharmacists and interdisciplinary/interprofessional content. The authors assessed each content area to determine accuracy and prioritized the need for updating, when applicable, to achieve consistency in descriptions and relevancy. The authors found that Wikipedia, a public domain that allows users to update, was consistently the most common Web site produced in search results. Results: The authors’ evaluation resulted in the creation or revision of 14 Wikipedia Web pages. However, rejection of 3 proposed newly created Web pages affected the authors’ ability to address identified content areas with deficiencies and/or inaccuracies. Conclusions: Through assessing and updating editable Web sites, the authors strengthened the online representation of clinical pharmacy in a clear, cohesive, and accurate manner. However, ongoing assessments of the Internet are continually needed to ensure accuracy and appropriateness

    On the "Mandelbrot set" for a pair of linear maps and complex Bernoulli convolutions

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    We consider the "Mandelbrot set" MM for pairs of complex linear maps, introduced by Barnsley and Harrington in 1985 and studied by Bousch, Bandt and others. It is defined as the set of parameters λ\lambda in the unit disk such that the attractor AλA_\lambda of the IFS {λz−1,λz+1}\{\lambda z-1, \lambda z+1\} is connected. We show that a non-trivial portion of MM near the imaginary axis is contained in the closure of its interior (it is conjectured that all non-real points of MM are in the closure of the set of interior points of MM). Next we turn to the attractors AλA_\lambda themselves and to natural measures Μλ\nu_\lambda supported on them. These measures are the complex analogs of much-studied infinite Bernoulli convolutions. Extending the results of Erd\"os and Garsia, we demonstrate how certain classes of complex algebraic integers give rise to singular and absolutely continuous measures Μλ\nu_\lambda. Next we investigate the Hausdorff dimension and measure of AλA_\lambda, for λ\lambda in the set MM, for Lebesgue-a.e. λ\lambda. We also obtain partial results on the absolute continuity of Μλ\nu_\lambda for a.e. λ\lambda of modulus greater than 1/2\sqrt{1/2}.Comment: 22 pages, 5 figure

    Socio-demographic variables, clinical features and the role of pre-assessment cross-sex hormones in older trans people

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    Introduction. As referrals to gender identity clinics have increased dramatically over the last few years, no studies focusing on older trans people seeking treatment are available. Aims. The aim of this study was to investigate the socio-demographic and clinical characteristics of older trans people attending a national service and to investigate the influence of cross-sex hormones (CHT) on psychopathology. Methods. Every individual over the age of 50 years old referred to a national gender identity clinic during a thirty months period were invited to complete a battery of questionnaires to measure psychopathology and clinical characteristics. Individuals on cross sex hormones prior to the assessment were compared with those not on treatment for different variables measuring psychopathology. Main Outcome Measures. Socio-demographic and clinical variables and measures of depression and anxiety (Hospital Anxiety and Depression Scale), self-esteem (Rosenberg Self-Esteem Scale), victimisation (Experiences of Transphobia Scale), social support (Multidimensional Scale of Perceived Social Support), interpersonal functioning (Inventory of Interpersonal Problems), and non-suicidal self-injury (Self-Injury Questionnaire). Results. The sex ratio of trans females aged 50 years and older compared to trans males was 23.7:1. Trans males were removed for the analysis due to their small number (n=3). Participants included 71 trans females over the age of 50, of whom the vast majority were white, employed or retired, divorced and had children. Trans females on CHT that came out as trans and transitioned at an earlier age, were significantly less anxious, reported higher levels of self-esteem and presented with less socialization problems. When controlling for socialization problems, differences in levels of anxiety but not self-esteem, remained. Conclusion. The use of cross-sex hormones prior to seeking treatment is widespread among older trans females and appears to be associated with psychological benefits. Existing barriers to access CHT for older trans people may need to be re-examined

    A two-domain elevator mechanism for sodium/proton antiport

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    Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general

    Driven diffusion in a periodically compartmentalized tube: homogeneity versus intermittency of particle motion

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    We study the effect of a driving force F on drift and diffusion of a point Brownian particle in a tube formed by identical ylindrical compartments, which create periodic entropy barriers for the particle motion along the tube axis. The particle transport exhibits striking features: the effective mobility monotonically decreases with increasing F, and the effective diffusivity diverges as F → ∞, which indicates that the entropic effects in diffusive transport are enhanced by the driving force. Our consideration is based on two different scenarios of the particle motion at small and large F, homogeneous and intermittent, respectively. The scenarios are deduced from the careful analysis of statistics of the particle transition times between neighboring openings. From this qualitative picture, the limiting small-F and large-F behaviors of the effective mobility and diffusivity are derived analytically. Brownian dynamics simulations are used to find these quantities at intermediate values of the driving force for various compartment lengths and opening radii. This work shows that the driving force may lead to qualitatively different anomalous transport features, depending on the geometry design
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