Minimal Seesaw as an Ultraviolet Insensitive Cure for the Problems of Anomaly Mediation

We show that an intermediate scale supersymmetric left-right seesaw scenario with automatic R-parity conservation can cure the problem of tachyonic slepton masses that arises when supersymmetry is broken by anomaly mediation, while preserving ultraviolet insensitivity. The reason for this is the existence of light B - L = 2 higgses with yukawa couplings to the charged leptons. We find these theories to have distinct predictions compared to the usual mSUGRA and gauge mediated models as well as the minimal AMSB models. Such predictions include a condensed gaugino mass spectrum and possibly a correspondingly condensed sfermion spectrum.Comment: 19 pages, 1 figur

Gauge Mediated SUSY Breaking via Seesaw

We present a simple scenario for gauge mediated supersymmetry breaking where the messengers are also the fields that generate neutrino masses. We show that the simplest such scenario corresponds to the case where neutrino masses are generated through the Type I and Type III seesaw mechanisms. The entire supersymmetric spectrum and Higgs masses are calculable from only four input parameters. Since the electroweak symmetry is broken through a doubly radiative mechanism, meaning a nearly zero B-term at the messenger scale which runs down to acceptable values, one obtains quite a constrained spectrum for the supersymmetric particles whose properties we describe. We refer to this mechanism as "nu-GMSB".Comment: a few corrections, references adde

Running with Triplets: How Slepton Masses Change With Doubly-Charged Higgses

We examine the slepton masses of SUSYLR models and how they change due the presence of light-doubly charged higgs bosons. We discover that the measurement of the slepton masses could bound and even predict the value of the third generation Yukawa coupling of leptons to the SU(2)_R Triplets. We also consider the unification prospects for this model with the addition of left-handed, B - L = 0 triplets--a model we call the Triplet Extended Supersymmetric Standard Model (TESSM). Finally, we discuss the changes in the slepton masses due to the presence of the SU(2)_L triplets.Comment: 20 pages, 6 figures, 4 table

Using Intervention Mapping to Develop an Efficacious Multicomponent Systems-Based Intervention to Increase Human Papillomavirus (HPV) Vaccination in a Large Urban Pediatric Clinic Network

Background: The CDC recommends HPV vaccine for all adolescents to prevent cervical, anal, oropharyngeal, vaginal, vulvar, and penile cancers, and genital warts. HPV vaccine rates currently fall short of national vaccination goals. Despite evidence-based strategies with demonstrated efficacy to increase HPV vaccination rates, adoption and implementation of these strategies within clinics is lacking. The Adolescent Vaccination Program (AVP) is a multicomponent systems-based intervention designed to implement five evidence-based strategies within primary care pediatric practices. The AVP has demonstrated efficacy in increasing HPV vaccine initiation and completion among adolescents 10-17 years of age. The purpose of this paper is to describe the application of Intervention Mapping (IM) toward the development, implementation, and formative evaluation of the clinic-based AVP prototype. Methods: Intervention Mapping (IM) guided the development of the Adolescent Vaccination Program (AVP). Deliverables comprised: a logic model of the problem (IM Step 1); matrices of behavior change objectives (IM Step 2); a program planning document comprising scope, sequence, theory-based methods, and practical strategies (IM Step 3); functional AVP component prototypes (IM Step 4); and plans for implementation (IM Step 5) and evaluation (IM Step 6). Results: The AVP consists of six evidence-based strategies implemented in a successful sequenced roll-out that (1) established immunization champions in each clinic, (2) disseminated provider assessment and feedback reports with data-informed vaccination goals, (3) provided continued medical and nursing education (with ethics credit) on HPV, HPV vaccination, message bundling, and responding to parent hesitancy, (4) electronic health record cues to providers on patient eligibility, and (5) patient reminders for HPV vaccine initiation and completion. Conclusions: IM provided a logical and systematic approach to developing and evaluating a multicomponent systems-based intervention to increase HPV vaccination rates among adolescents in pediatric clinics

Yersinia pestis insecticidal-like toxin complex (Tc) family proteins: characterization of expression, subcellular localization, and potential role in infection of the flea vector

BACKGROUND: Toxin complex (Tc) family proteins were first identified as insecticidal toxins in Photorhabdus luminescens and have since been found in a wide range of bacteria. The genome of Yersinia pestis, the causative agent of bubonic plague, contains a locus that encodes the Tc protein homologues YitA, YitB, YitC, and YipA and YipB. Previous microarray data indicate that the Tc genes are highly upregulated by Y. pestis while in the flea vector; however, their role in the infection of fleas and pathogenesis in the mammalian host is unclear. RESULTS: We show that the Tc proteins YitA and YipA are highly produced by Y. pestis while in the flea but not during growth in brain heart infusion (BHI) broth at the same temperature. Over-production of the LysR-type regulator YitR from an exogenous plasmid increased YitA and YipA synthesis in broth culture. The increase in production of YitA and YipA correlated with the yitR copy number and was temperature-dependent. Although highly synthesized in fleas, deletion of the Tc proteins did not alter survival of Y. pestis in the flea or prevent blockage of the proventriculus. Furthermore, YipA was found to undergo post-translational processing and YipA and YitA are localized to the outer membrane of Y. pestis. YitA was also detected by immunofluorescence microscopy on the surface of Y. pestis. Both YitA and YipA are produced maximally at low temperature but persist for several hours after transfer to 37°C. CONCLUSIONS: Y. pestis Tc proteins are highly expressed in the flea but are not essential for Y. pestis to stably infect or produce a transmissible infection in the flea. However, YitA and YipA localize to the outer membrane and YitA is exposed on the surface, indicating that at least YitA is present on the surface when Y. pestis is transmitted into the mammalian host from the flea

Electromagnetic controlled cortical impact device for precise, graded experimental traumatic brain injury

Genetically modified mice represent useful tools for traumatic brain injury (TBI) research and attractive preclinical models for the development of novel therapeutics. Experimental methods that minimize the number of mice needed may increase the pace of discovery. With this in mind, we developed and characterized a prototype electromagnetic (EM) controlled cortical impact device along with refined surgical and behavioral testing techniques. By varying the depth of impact between 1.0 and 3.0 mm, we found that the EM device was capable of producing a broad range of injury severities. Histologically, 2.0-mm impact depth injuries produced by the EM device were similar to 1.0-mm impact depth injuries produced by a commercially available pneumatic device. Behaviorally, 2.0-, 2.5-, and 3.0-mm impacts impaired hidden platform and probe trial water maze performance, whereas 1.5-mm impacts did not. Rotorod and visible platform water maze deficits were also found following 2.5- and 3.0-mm impacts. No impairment of conditioned fear performance was detected. No differences were found between sexes of mice. Inter-operator reliability was very good. Behaviorally, we found that we could statistically distinguish between injury depths differing by 0.5 mm using 12 mice per group and between injury depths differing by 1.0 mm with 7-8 mice per group. Thus, the EM impactor and refined surgical and behavioral testing techniques may offer a reliable and convenient framework for preclinical TBI research involving mice

When Anomaly Mediation is UV Sensitive

Despite its successes---such as solving the supersymmetric flavor problem---anomaly mediated supersymmetry breaking is untenable because of its prediction of tachyonic sleptons. An appealing solution to this problem was proposed by Pomarol and Rattazzi where a threshold controlled by a light field deflects the anomaly mediated supersymmetry breaking trajectory, thus evading tachyonic sleptons. In this paper we examine an alternate class of deflection models where the non-supersymmetric threshold is accompanied by a heavy, instead of light, singlet. The low energy form of this model is the so-called extended anomaly mediation proposed by Nelson and Weiner, but with potential for a much higher deflection threshold. The existence of this high deflection threshold implies that the space of anomaly mediated supersymmetry breaking deflecting models is larger than previously thought.Comment: 14 pages, 1 figure (version to appear in JHEP

P-glycoprotein deficiency at the blood-brain barrier increases amyloid-β deposition in an Alzheimer disease mouse model

Accumulation of amyloid-β (Aβ) within extracellular spaces of the brain is a hallmark of Alzheimer disease (AD). In sporadic, late-onset AD, there is little evidence for increased Aβ production, suggesting that decreased elimination from the brain may contribute to elevated levels of Aβ and plaque formation. Efflux transport of Aβ across the blood-brain barrier (BBB) contributes to Aβ removal from the brain. P-glycoprotein (Pgp) is highly expressed on the luminal surface of brain capillary endothelial cells and contributes to the BBB. In Pgp-null mice, we show that [(125)I]Aβ(40) and [(125)I]Aβ(42) microinjected into the CNS clear at half the rate that they do in WT mice. When amyloid precursor protein–transgenic (APP-transgenic) mice were administered a Pgp inhibitor, Aβ levels within the brain interstitial fluid significantly increased within hours of treatment. Furthermore, APP-transgenic, Pgp-null mice had increased levels of brain Aβ and enhanced Aβ deposition compared with APP-transgenic, Pgp WT mice. These data establish a direct link between Pgp and Aβ metabolism in vivo and suggest that Pgp activity at the BBB could affect risk for developing AD as well as provide a novel diagnostic and therapeutic target

Considering Intra-individual Genetic Heterogeneity to Understand Biodiversity

In this chapter, I am concerned with the concept of Intra-individual Genetic Hetereogeneity (IGH) and its potential influence on biodiversity estimates. Definitions of biological individuality are often indirectly dependent on genetic sampling -and vice versa. Genetic sampling typically focuses on a particular locus or set of loci, found in the the mitochondrial, chloroplast or nuclear genome. If ecological function or evolutionary individuality can be defined on the level of multiple divergent genomes, as I shall argue is the case in IGH, our current genetic sampling strategies and analytic approaches may miss out on relevant biodiversity. Now that more and more examples of IGH are available, it is becoming possible to investigate the positive and negative effects of IGH on the functioning and evolution of multicellular individuals more systematically. I consider some examples and argue that studying diversity through the lens of IGH facilitates thinking not in terms of units, but in terms of interactions between biological entities. This, in turn, enables a fresh take on the ecological and evolutionary significance of biological diversity

The Democratic Biopolitics of PrEP

PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts ‘sexual-somatic ethics’ and ‘democratic biopolitics’, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. ‘Biopolitical democratization’ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma