Radiative Electroweak Symmetry Breaking in a Little Higgs Model

We present a new Little Higgs model, motivated by the deconstruction of a five-dimensional gauge-Higgs model. The approximate global symmetry is $SO(5)_0\times SO(5)_1$, breaking to $SO(5)$, with a gauged subgroup of $[SU(2)_{0L}\times U(1)_{0R}]\times O(4)_1$, breaking to $SU(2)_L \times U(1)_Y$. Radiative corrections produce an additional small vacuum misalignment, breaking the electroweak symmetry down to $U(1)_{EM}$. Novel features of this model are: the only un-eaten pseudo-Goldstone boson in the effective theory is the Higgs boson; the model contains a custodial symmetry, which ensures that $\hat{T}=0$ at tree-level; and the potential for the Higgs boson is generated entirely through one-loop radiative corrections. A small negative mass-squared in the Higgs potential is obtained by a cancellation between the contribution of two heavy partners of the top quark, which is readily achieved over much of the parameter space. We can then obtain both a vacuum expectation value of $v=246$ GeV and a light Higgs boson mass, which is strongly correlated with the masses of the two heavy top quark partners. For a scale of the global symmetry breaking of $f=1$ TeV and using a single cutoff for the fermion loops, the Higgs boson mass satisfies 120 GeV $\lesssim M_H\lesssim150$ GeV over much of the range of parameter space. For $f$ raised to 10 TeV, these values increase by about 40 GeV. Effects at the ultraviolet cutoff scale may also raise the predicted values of the Higgs boson mass, but the model still favors $M_H\lesssim 200$ GeV.Comment: 32 pages, 10 figures, JHEP style. Version accepted for publication in JHEP. Includes additional discussion of sensitivity to UV effects and fine-tuning, revised Fig. 9, added appendix and additional references

Decoupling property of the supersymmetric Higgs sector with four doublets

In supersymmetric standard models with multi Higgs doublet fields, selfcoupling constants in the Higgs potential come only from the D-terms at the tree level. We investigate the decoupling property of additional two heavier Higgs doublet fields in the supersymmetric standard model with four Higgs doublets. In particular, we study how they can modify the predictions on the quantities well predicted in the minimal supersymmetric standard model (MSSM), when the extra doublet fields are rather heavy to be measured at collider experiments. The B-term mixing between these extra heavy Higgs bosons and the relatively light MSSM-like Higgs bosons can significantly change the predictions in the MSSM such as on the masses of MSSM-like Higgs bosons as well as the mixing angle for the two light CP-even scalar states. We first give formulae for deviations in the observables of the MSSM in the decoupling region for the extra two doublet fields. We then examine possible deviations in the Higgs sector numerically, and discuss their phenomenological implications.Comment: 26 pages, 24 figures, text sligtly modified,version to appear in Journal of High Energy Physic

Cost-Effectiveness of Preoperative Screening and Eradication of Staphylococcus aureus Carriage

BACKGROUND: Preoperative screening for nasal S. aureus carriage, followed by eradication treatment of identified carriers with nasal mupirocine ointment and chlorhexidine soap was highly effective in preventing deep-seated S. aureus infections. It is unknown how cost-effectiveness of this intervention is affected by suboptimal S. aureus screening. We determined cost-effectiveness of different preoperative S. aureus screening regimes. METHODS: We compared different screening scenarios (ranging from treating all patients without screening to treating only identified S. aureus carriers) to the base case scenario without any screening and treatment. Screening and treatment costs as well as costs and mortality due to deep-seated S. aureus infection were derived from hospital databases and prospectively collected data, respectively. RESULTS: As compared to the base case scenario, all scenarios are associated with improved health care outcomes at reduced costs. Treating all patients without screening is most cost-beneficial, saving €7339 per life year gained, as compared to €3330 when only identified carriers are treated. In sensitivity analysis, outcomes are susceptible to the sensitivity of the screening test and the efficacy of treatment. Reductions in these parameters would reduce the cost-effectiveness of scenarios in which treatment is based on screening. When only identified S. aureus carriers are treated costs of screening should be less than €6.23 to become the dominant strategy. CONCLUSIONS: Preoperative screening and eradication of S. aureus carriage to prevent deep-seated S. aureus infections saves both life years and medical costs at the same time, although treating all patients without screening is the dominant strategy, resulting in most health gains and largest savings

Frequency-Invariant Representation of Interaural Time Differences in Mammals

Interaural time differences (ITDs) are the major cue for localizing low-frequency sounds. The activity of neuronal populations in the brainstem encodes ITDs with an exquisite temporal acuity of about . The response of single neurons, however, also changes with other stimulus properties like the spectral composition of sound. The influence of stimulus frequency is very different across neurons and thus it is unclear how ITDs are encoded independently of stimulus frequency by populations of neurons. Here we fitted a statistical model to single-cell rate responses of the dorsal nucleus of the lateral lemniscus. The model was used to evaluate the impact of single-cell response characteristics on the frequency-invariant mutual information between rate response and ITD. We found a rough correspondence between the measured cell characteristics and those predicted by computing mutual information. Furthermore, we studied two readout mechanisms, a linear classifier and a two-channel rate difference decoder. The latter turned out to be better suited to decode the population patterns obtained from the fitted model

Resistance Status of the Malaria Vector Mosquitoes, Anopheles stephensi and Anopheles subpictus Towards Adulticides and Larvicides in Arid and Semi-Arid Areas of India

Susceptibility studies of malaria vectors Anopheles stephensi Liston (Diptera: Culicidae) and An. subpictus Grassi collected during 2004–2007 from various locations of Arid and Semi-Arid Zone of India were conducted by adulticide bioassay of DDT, malathion, deltamethrin and larvicide bioassay of fenthion, temephos, chlorpyriphos and malathion using diagnostic doses. Both species from all locations exhibited variable resistance to DDT and malathion from majority of location. Adults of both the species were susceptible to Deltamethrin. Larvae of both the Anopheline species showed some evidence of resistance to chlorpyriphos followed by fenthion whereas susceptible to temephos and malathion

Triplet Repeat–Derived siRNAs Enhance RNA–Mediated Toxicity in a Drosophila Model for Myotonic Dystrophy

More than 20 human neurological and neurodegenerative diseases are caused by simple DNA repeat expansions; among these, non-coding CTG repeat expansions are the basis of myotonic dystrophy (DM1). Recent work, however, has also revealed that many human genes have anti-sense transcripts, raising the possibility that human trinucleotide expansion diseases may be comprised of pathogenic activities due both to a sense expanded-repeat transcript and to an anti-sense expanded-repeat transcript. We established a Drosophila model for DM1 and tested the role of interactions between expanded CTG transcripts and expanded CAG repeat transcripts. These studies revealed dramatically enhanced toxicity in flies co-expressing CTG with CAG expanded repeats. Expression of the two transcripts led to novel pathogenesis with the generation of dcr-2 and ago2-dependent 21-nt triplet repeat-derived siRNAs. These small RNAs targeted the expression of CAG-containing genes, such as Ataxin-2 and TATA binding protein (TBP), which bear long CAG repeats in both fly and man. These findings indicate that the generation of triplet repeat-derived siRNAs may dramatically enhance toxicity in human repeat expansion diseases in which anti-sense transcription occurs

Dissecting the Autocrine and Paracrine Roles of the CCR2-CCL2 Axis in Tumor Survival and Angiogenesis

The CCL2 CCR2 axis is likely to contributes to the development and progression of cancer diseases by two major mechanisms; autocrine effect of CCL2 as a survival/growth factor for CCR2+ cancer cells and, the attraction of CCR2+ CX3CR1+tumor associated macrophages that in the absence of CCR2 hardly migrate. Thus far no in vivo system has been set up to differentiate the selective contribution of each of these features to cancer development. Here we employed a chimera animal model in which all non-malignant cells are CCR2−/−, but all cancer cells are CCR2+, combined with an adoptive transfer system of bone marrow (BM) CX3CR1+ cells from CCR2+ mice harboring a targeted replacement of the CX3CR1gene by an enhanced green fluorescent protein (EGFP) reporter gene (cx3cr1gfp), together with the CD45.1 congene. Using this system we dissected the selective contribution of CX3CR1+CCR2+ cells, which comprise only about 7% of CD11b+ BM cells, to tumor development and angiogenesis. Showing that aside for their direct pro-angiogenic effect they are essential for the recruitment of other CD11b+ cells to the tumor site. We further show that the administration of CCR2-Ig, that selectively and specifically neutralize CCL2, to mice in which CCR2 is expressed only on tumor cells, further suppressed tumor development, implicating for the key role of this chemokine supporting tumor survival in an autocrine manner. This further emphasizes the important role of CCL2 as a target for therapy of cancer diseases

Angiopreventive Efficacy of Pure Flavonolignans from Milk Thistle Extract against Prostate Cancer: Targeting VEGF-VEGFR Signaling

The role of neo-angiogenesis in prostate cancer (PCA) growth and metastasis is well established, but the development of effective and non-toxic pharmacological inhibitors of angiogenesis remains an unaccomplished goal. In this regard, targeting aberrant angiogenesis through non-toxic phytochemicals could be an attractive angiopreventive strategy against PCA. The rationale of the present study was to compare the anti-angiogenic potential of four pure diastereoisomeric flavonolignans, namely silybin A, silybin B, isosilybin A and isosilybin B, which we established previously as biologically active constituents in Milk Thistle extract. Results showed that oral feeding of these flavonolignans (50 and 100 mg/kg body weight) effectively inhibit the growth of advanced human PCA DU145 xenografts. Immunohistochemical analyses revealed that these flavonolignans inhibit tumor angiogenesis biomarkers (CD31 and nestin) and signaling molecules regulating angiogenesis (VEGF, VEGFR1, VEGFR2, phospho-Akt and HIF-1α) without adversely affecting the vessel-count in normal tissues (liver, lung, and kidney) of tumor bearing mice. These flavonolignans also inhibited the microvessel sprouting from mouse dorsal aortas ex vivo, and the VEGF-induced cell proliferation, capillary-like tube formation and invasiveness of human umbilical vein endothelial cells (HUVEC) in vitro. Further studies in HUVEC showed that these diastereoisomers target cell cycle, apoptosis and VEGF-induced signaling cascade. Three dimensional growth assay as well as co-culture invasion and in vitro angiogenesis studies (with HUVEC and DU145 cells) suggested the differential effectiveness of the diastereoisomers toward PCA and endothelial cells. Overall, these studies elucidated the comparative anti-angiogenic efficacy of pure flavonolignans from Milk Thistle and suggest their usefulness in PCA angioprevention

MUC4 mucin expression in human pancreatic tumours is affected by organ environment: the possible role of TGFβ2

MUC4 is highly expressed in human pancreatic tumours and pancreatic tumour cell lines, but is minimally or not expressed in normal pancreas or chronic pancreatitis. Here, we investigated the aberrant regulation of MUC4 expression in vivo using clonal human pancreatic tumour cells (CD18/HPAF) grown either orthotopically in the pancreas (OT) or ectopically in subcutaneous tissue (SC) in the nude mice. Histological examination of the OT and SC tumours showed moderately differentiated and anaplastic morphology, respectively. The OT tumour cells showed metastases to distant lymph nodes and faster tumour growth (