Clash of symmetries on the brane

If our 3+1-dimensional universe is a brane or domain wall embedded in a higher dimensional space, then a phenomenon we term the ``clash of symmetries'' provides a new method of breaking some continuous symmetries. A global $G_{\text{cts}} \otimes G_{\text{discrete}}$ symmetry is spontaneously broken to $H_{\text{cts}} \otimes H_{\text{discrete}}$, where the continuous subgroup $H_{\text{cts}}$ can be embedded in several different ways in the parent group $G_{\text{cts}}$, and $H_{\text{discrete}} < G_{\text{discrete}}$. A certain class of topological domain wall solutions connect two vacua that are invariant under {\it differently embedded} $H_{\text{cts}}$ subgroups. There is then enhanced symmetry breakdown to the intersection of these two subgroups on the domain wall. This is the ``clash''. In the brane limit, we obtain a configuration with $H_{\text{cts}}$ symmetries in the bulk but the smaller intersection symmetry on the brane itself. We illustrate this idea using a permutation symmetric three-Higgs-triplet toy model exploiting the distinct $I-$, $U-$ and $V-$spin U(2) subgroups of U(3). The three disconnected portions of the vacuum manifold can be treated symmetrically through the construction of a three-fold planar domain wall junction configuration, with our universe at the nexus. A possible connection with $E_6$ is discussed.Comment: 30 pages, 9 embedded figure

Pengaruh Arus terhadap Sebaran Material Padatan Tersuspensi di PT. Pertamina Ru VI Perairan Balongan, Kabupaten Indramayu, Jawa Barat

Aktivitas pada pelabuhan khusus PT. Pertamina RU VI Balongan Indramayu menyebabkan kondisi perairan di sekitar lokasi pelabuhan menjadi dinamis. Proses hidro-oseanografi memberikan pengaruh terhadap tingginya suatu nilai padatan tersuspensi di suatu lokasi. Dalam hal ini perlu dilakukan penelitian mengenai pola arus laut terhadap sebaran material padatan tersuspensi di PT. Pertamina RU VI Perairan Balongan Indramayu, Jawa Barat. Tujuan dilakukannya penelitian ini adalah untuk mengetahui pengaruh arus laut terhadap sebaran MPT di PT. Pertamina RU VI Perairan Balongan Indramayu. Penelitian dimulai dari tahap pengambilan data di lapangan pada tanggal 8-15 November 2014 di PT. Pertamina RU VI Perairan Balongan Indramayu dan tahap pengolahan data serta analisis data hasil pengukuran lapangan. Materi yang digunakan meliputi data primer berupa arus dan sampel air sedangkan data sekunder berupa data pasut dan peta batimetri Tanjungpriok hingga Cirebon. Penelitian ini menggunakan metode deskriptif yang bersifat eksploratif, penentuan lokasi pengambilan sampel air menggunakan metode sampling purposive, pengambilan data arus menggunakan metode lagrange. Model matematik yang digunakan adalah model ADCIRC untuk pola arus dan ArcGIS untuk sebaran MPT. Berdasarkan hasil sebaran MPT di PT. Pertamina RU VI Perairan Balongan mempunyai nilai konsentrasi rerata MPT pada saat menuju pasang sebesar 122 mg/l dan saat menuju surut sebesar 89 mg/l. Dalam proses penyebaran nilai konsentrasi di perairan tidak hanya dipengaruhi oleh arus melainkan ada faktor lain, yaitu faktor kedalaman dan aktivitas kapal

Goal-directed versus outcome-based financial incentives for weight loss among low-income patients with obesity: rationale and design of the Financial Incentives foR Weight Reduction (FIReWoRk) randomised controlled trial.

IntroductionObesity is a major public health challenge and exacerbates economic disparities through employment discrimination and increased personal health expenditures. Financial incentives for weight management may intensify individuals' utilisation of evidence-based behavioural strategies while addressing obesity-related economic disparities in low-income populations. Trials have focused on testing incentives contingent on achieving weight loss outcomes. However, based on social cognitive and self-determination theories, providing incentives for achieving intermediate behavioural goals may be more sustainable than incentivising outcomes if they enhance an individual's skills and self-efficacy for maintaining long-term weight loss. The objective of this paper is to describe the rationale and design of the Financial Incentives foR Weight Reduction study, a randomised controlled trial to test the comparative effectiveness and cost-effectiveness of two financial incentive strategies for weight loss (goal directed vs outcome based) among low-income adults with obesity, as well as compared with the provision of health behaviour change resources alone.Methods and analysisWe are recruiting 795 adults, aged 18-70 years with a body mass index ≥30 kg/m2, from three primary care clinics serving residents of socioeconomically disadvantaged neighbourhoods in New York City and Los Angeles. All participants receive a 1-year commercial weight loss programme membership, self-monitoring tools (bathroom scale, food journal and Fitbit Alta HR), health education and monthly check-in visits. In addition to these resources, those in the two intervention groups can earn up to $750 over 6 months for: (1) participating in an intensive weight management programme, self-monitoring weight and diet and meeting physical activity guidelines (goal-directed arm); or (2) a ≥1.5% to ≥5% reduction in baseline weight (outcome-based arm). To maximise incentive efficacy, we incorporate concepts from behavioural economics, including immediacy of payments and framing feedback to elicit regret aversion. We will use generalised mixed effect models for repeated measures to examine intervention effects on weight at 6, 9 and 12 months.Ethics and disseminationHuman research protection committees at New York University School of Medicine, University of California Los Angeles (UCLA) David Geffen School of Medicine and Olive-View-UCLA Medical Center granted ethics approval. We will disseminate the results of this research via peer-reviewed publications, conference presentations and meetings with stakeholders.Trial registration numberNCT03157713

Enhanced antiproliferative and apoptotic response to combined treatment of γ-tocotrienol with erlotinib or gefitinib in mammary tumor cells

BACKGROUND: Aberrant ErbB receptor signaling is associated with various types of malignancies. γ-Tocotrienol is a member of the vitamin E family of compounds that displays potent anticancer activity that is associated with suppression in ErbB receptor phosphorylation and mitogenic signaling. Erlotinib and gefitinib are tyrosine kinase inhibitors that block ErbB1 receptor activation, whereas trastuzumab is a monoclonal antibody that has been designed to specifically inhibit ErbB2 receptor activation. However, the clinical effectiveness of these agents have been disappointing because of cooperation between different ErbB family members that can rescue cancer cells from agents directed against a single ErbB receptor subtype. It was hypothesized that targeting multiple ErbB receptor subtypes with combined treatment of γ-tocotrienol and ErbB receptor inhibitors would provide greater anticancer effects than monotherapy targeting only a single ErbB receptor subtype. METHODS: Highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined media containing 10 ng/ml EGF as a mitogen. Cell viability wase determined by MTT assay, whereas Western blot and immunofluorescent staining was used to determine treatment effects on ErbB receptor subtype level and activation. Treatment-induced apoptosis was determined using annexin V staining and Western blot analysis of cleaved caspase-3 and PARP levels. RESULTS: Treatment with 3.5 μM γ-tocotrienol, 0.5 μM erlotinib or 1.0 μM gefitinib alone, significantly inhibited +SA tumor cell growth. Combined treatment with subeffective doses of erlotinib (0.25 μM) or gefitinib (0.5 μM) with subeffective doses of γ-tocotrienol (0.5-3.0 μM) significantly inhibited the growth and induced apoptosis in a dose-responsive manner. Trastuzumab treatment alone or in combination had no effect on +SA cell growth and viability. Combined treatment of γ-tocotrienol with erlotinib or gefitinib also cause a large decrease in ErbB3, ErbB4, and to a lesser extent ErbB2 receptor levels, and EGF-dependent ErbB2-4 tyrosine phosphorylation (activation), but had no effect on ErbB1 receptor levels or activation. CONCLUSION: Combination treatment of γ-tocotrienol with specific ErbB receptor inhibitors is more effective in reducing mammary tumor cell growth and viability than high dose monotherapy, suggesting that targeting multiple ErbB receptors with combination therapy may significantly improve the therapeutic response in breast cancer patients

Light-Heavy Symmetry: Geometric Mass Hierarchy for Three Families

The Universal Seesaw pattern coupled with a Light$\leftrightarrow$Heavy symmetry principle leads to the Diophantine equation $\displaystyle N = \sum_{i=1}^Nn_i$, where $n_i\geq 0$ and distinct. Its unique non-trivial solution $(3=0+1+2)$ gives rise to the geometric mass hierarchy $m_W$, $m_W\epsilon$, $m_W\epsilon^2$ for $N=3$ fermion families. This is realized in a model where the hybrid (yet Up$\leftrightarrow$Down symmetric) quark mass relations $m_d m_t \approx m_c^2\leftrightarrow m_u m_b \approx m_s^2$ play a crucial role in expressing the CKM mixings in terms of simple mass ratios, notably $\sin\theta_C \approx {m_c\over m_b}$.Comment: 12 pages, no figures, Revtex fil

Non-Abelian Monopole and Dyon Solutions in a Modified Einstein-Yang-Mills-Higgs System

We have studied a modified Yang-Mills-Higgs system coupled to Einstein gravity. The modification of the Einstein-Hilbert action involves a direct coupling of the Higgs field to the scalar curvature. In this modified system we are able to write a Bogomol'nyi type condition in curved space and demonstrate that the positive static energy functional is bounded from below. We then investigate non-Abelian sperically symmetric static solutions in a similar fashion to the `t Hooft-Polyakov monopole. After reviewing previously studied monopole solutions of this type, we extend the formalism to included electric charge and we present dyon solutions.Comment: 18 pages LaTeX, 7 eps-figure

miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype with no clinically proven biologically targeted treatment options. The molecular heterogeneity of TNBC and lack of high frequency driver mutations other than TP53 have hindered the development of new and effective therapies that significantly improve patient outcomes. miRNAs, global regulators of survival and proliferation pathways important in tumor development and maintenance, are becoming promising therapeutic agents. We performed miRNA-profiling studies in different TNBC subtypes to identify miRNAs that significantly contribute to disease progression. We found that miR-34a was lost in TNBC, specifically within mesenchymal and mesenchymal stem cell-like subtypes, whereas expression of miR-34a targets was significantly enriched. Furthermore, restoration of miR-34a in cell lines representing these subtypes inhibited proliferation and invasion, activated senescence, and promoted sensitivity to dasatinib by targeting the proto-oncogene c-SRC. Notably, SRC depletion in TNBC cell lines phenocopied the effects of miR-34a reintroduction, whereas SRC overexpression rescued the antitumorigenic properties mediated by miR-34a. miR-34a levels also increased when cells were treated with c-SRC inhibitors, suggesting a negative feedback exists between miR-34a and c-SRC. Moreover, miR-34a administration significantly delayed tumor growth of subcutaneously and orthotopically implanted tumors in nude mice, and was accompanied by c-SRC downregulation. Finally, we found that miR-34a and SRC levels were inversely correlated in human tumor specimens. Together, our results demonstrate that miR-34a exerts potent antitumorigenic effects in vitro and in vivo and suggests that miR-34a replacement therapy, which is currently being tested in human clinical trials, represents a promising therapeutic strategy for TNBC. Cancer Res; 76(4); 1-13. (c)2015 AACR

Serum Antioxidant Vitamins Levels in Children with Sickle Cell Anaemia in Sokoto, North Western Nigeria

Sickle cell anaemia is associated with elevated oxidative stress via increase generation of reactive oxygen species (ROS), and decline in antioxidant defences. Increased oxidative stress is thought to play a role in the development of sickle cell anaemic complications. In the current study, vitamins A, C, and E levels were estimated in 35 sickle cell anaemics attending the Paediatric medical clinic of the Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria and the results compared with those of apparently healthy non-sickle cell anaemic volunteers of comparable age and social status. Serum levels of vitamin A, C, and E were 31.06 ± 2.97 μg/dl, 0.27 ± 0.05 mg/dl, 0.20 ± 0.01 mg/dl and 69.51 ± 4.54 μg/dl, 0.77 ± 0.10 mg/dl and 0.49 ± 0.02 mg/dl in sickle cell anaemics and non- sickle cell anaemic subjects respectively. There was significantly (P&lt;0.05) decreased levels of antioxidant vitamins in sickle cell anaemic subjects. Age and gender did not have significant (P&gt;0.05) difference. The results suggest that sickle cell anaemics in the study area have low serum levels of antioxidant vitamins, an indication that the sickle cell anaemics are predisposed to increased oxidative onslaught.Keywords: Sickle cell anaemia, serum vitamins A, C, and E

Einstein's quantum theory of the monatomic ideal gas: non-statistical arguments for a new statistics

In this article, we analyze the third of three papers, in which Einstein presented his quantum theory of the ideal gas of 1924-1925. Although it failed to attract the attention of Einstein's contemporaries and although also today very few commentators refer to it, we argue for its significance in the context of Einstein's quantum researches. It contains an attempt to extend and exhaust the characterization of the monatomic ideal gas without appealing to combinatorics. Its ambiguities illustrate Einstein's confusion with his initial success in extending Bose's results and in realizing the consequences of what later became to be called Bose-Einstein statistics. We discuss Einstein's motivation for writing a non-combinatorial paper, partly in response to criticism by his friend Ehrenfest, and we paraphrase its content. Its arguments are based on Einstein's belief in the complete analogy between the thermodynamics of light quanta and of material particles and invoke considerations of adiabatic transformations as well as of dimensional analysis. These techniques were well-known to Einstein from earlier work on Wien's displacement law, Planck's radiation theory, and the specific heat of solids. We also investigate the possible role of Ehrenfest in the gestation of the theory.Comment: 57 pp

Detection of early age-related macular degeneration using novel functional parameters of the focal cone electroretinogram

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration