Signals of New Gauge Bosons in Gauged Two Higgs Doublet Model

Recently a gauged two Higgs doublet model, in which the two Higgs doublets are embedded into the fundamental representation of an extra local $SU(2)_H$ group, is constructed. Both the new gauge bosons $Z^\prime$ and $W^{\prime (p,m)}$ are electrically neutral. While $Z^\prime$ can be singly produced at colliders, $W^{\prime (p,m)}$, which is heavier, must be pair produced. We explore the constraints of $Z^\prime$ using the current Drell-Yan type data from the Large Hadron Collider. Anticipating optimistically that $Z^\prime$ can be discovered via the clean Drell-Yan type signals at high luminosity upgrade of the collider, we explore the detectability of extra heavy fermions in the model via the two leptons/jets plus missing transverse energy signals from the exotic decay modes of $Z^\prime$. For the $W^{\prime (p,m)}$ pair production in a future 100 TeV proton-proton collider, we demonstrate certain kinematical distributions for the two/four leptons plus missing energy signals have distinguishable features from the Standard Model background. In addition, comparisons of these kinematical distributions between the gauged two Higgs doublet model and the littlest Higgs model with T-parity, the latter of which can give rise to the same signals with competitive if not larger cross sections, are also presented.Comment: 39 pages, 23 figures, 7 tables and two new appendixes, to appear in EPJ

Cortical development & plasticity in the FMRP KO mouse

Autism is one of the leading causes of human intellectual disability (ID). More than 1% of the human population has autism spectrum disorders (ASDs), and it has been estimated that over 50% of those with ASDs also have ID. Fragile X syndrome (FXS) is the most common inherited form of mental retardation and is the leading known genetic cause of autism, affecting approximately 1 in 4000 males and 1 in 8000 females. Approximately 30% of boys with FXS will be diagnosed with autism in their later lives. The cause of FXS is through an over-expansion of the CGG trinucleotide repeat located at the 5’ untranslated region of the FMR1 gene, leading to hypermethylation of the surrounding sequence and eventually partially or fully silencing of the gene. Therefore, the protein product of the gene, fragile X mental retardation protein (FMRP), is reduced or missing. As a single-gene disorder, FXS offers a scientifically tractable way to examine the underlying mechanism of the disease and also shed some light on understanding ASD and ID. The mouse model of FXS (Fmr1−/y mice) is widely accepted and used as a good model, offering good structural and face validity. Since a primary deficit of FXS is believed to be altered neuronal communication, in this thesis I examined white matter tract and dendritic spine abnormalities in the mouse model of FXS. Loss of FMRP does not alter the gross morphology of the white matter. However, recent brain imaging studies indicated that loss of FMRP could lead to some minute abnormalities in different major white matter tracts in the human brain. The gross white matter morphology and myelination was unaltered in the Fmr1−/y mice, however, a small but significant increase of axon diameter in the corpus callosum (CC) was found compared to wild-type (WT) controls. Our computation model suggested that the increase of axon diameter in the Fmr1−/y mice could lead to an increase of conduction velocity in these animals. One of the key phenotypes reported previously in the loss of FMRP is the increase of “immature” dendritic spines. The increase of long and thin spines was reported in several brain regions including the somatosensory cortex and visual cortex in both FXS patients and the mouse model of FXS. Although recent studies which employed state-of-the-art microscopy techniques suggested that only minute differences were noticed between the WT and Fmr1−/y mice. In agreement with previous findings, I found an increase of dendritic spine density in the visual cortex in the Fmr1−/y mice, and spine morphology was also different between the two genotypes. We found that the spine head diameter is significantly increased in the CA1 area of the apical dendrites of the Fmr1−/y mice compared to WT controls. Dendritic spine length is also significantly increased in the same region of the Fmr1−/y mice. However, apical spine head size does not alter between the two genotypes in the V1 region of the visual cortex, and spine length is significantly decreased in the Fmr1−/y mice compared to WT animals in this region. Lovastatin, a drug known as one of the 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors, functions as a modulator of the mitogen-activated protein kinases (MAPK) pathway through inhibiting Ras farnesylation, was used in an attempt to rescue the dendritic spine abnormalities in the Fmr1−/y mice. Mice lacking FMRP are susceptible to audiogenic seizure (AGS). Previous work has shown that 48 hr of lovastatin treatment reduced the incidence of AGS in the Fmr1−/y mice. However, chronic lovastatin treatment failed to rescue the spine density and morphology abnormalities in the Fmr1−/y mice. Mouse models are invaluable tools for modelling human diseases. However inter-strain differences have often confounded results between laboratories. In my final Chapter of this thesis, I compared two commonly used C57BL/6 substrains of mice by recording their electrophysiological responses to visual stimuli in vivo. I found a significant increase of high-frequency gamma power in adult C57BL/6JOla mice, and this phenomenon was reduced during the critical period. My results suggested that the C57BL/6JOla substrain has a significant stronger overall inhibitory network activity in the visual cortex than the C57BL/6J substrain. This is in good agreement with previous findings showing a lack of open-eye potentiation to monocular deprivation in the C57BL/6JOla substrain, and highlights the need for appropriate choice of mouse strain when studying neurodevelopmental models. They also give valuable insights into the genetic mechanisms that permit experience-dependent developmental plasticity. In summary, these findings give us a better understanding of the fine structure abnormalities of the Fmr1−/y mice, which in turn can benefit future discoveries of the underlying mechanisms of neurodevelopmental disorders such as ID and ASDs

Distant-Time Location Prediction in Low-Sampling-Rate Trajectories

Abstract—With the growth of location-based services and social services, low-sampling-rate trajectories from check-in data or photos with geo-tag information becomes ubiquitous. In general, most detailed moving information in low-sampling-rate trajectories are lost. Prior works have elaborated on distant-time location prediction in high-sampling-rate trajectories. However, existing prediction models are pattern-based and thus not ap-plicable due to the sparsity of data points in low-sampling-rate trajectories. For example, it becomes difficult to derive trajectory patterns, let alone utilizing trajectory patterns for distant-time location prediction. In this paper, given a query time, the current location and time, we aim to predict the location of an object at the query time. To address the sparsity in low-sampling-rate trajectories, we develop a Reachability-based prediction model on Time-constrained Mobility Graph (abbreviated as RTMG) to predict locations for distant-time queries. Specifically, we design an adaptive temporal exploration approach to extract effective supporting trajectories that are temporally close to the query time. These data points are then represented as a Time-constrained user mobility Graph (refers to as TG). In light of TG, we further derive the reachability probabilities among locations in TG. Thus, a location with maximum reachability from the current location among all possible locations in sup-porting trajectories is considered as the prediction result. To efficiently process queries, we proposed an index structure SOIT to organize location records for on-line query processing. We conduct extensive experiments on real low-sampling-rate datasets and demonstrate the effectiveness and efficiency of RTMG. I

Chinese Herbal Medicine as an Adjunctive Therapy Ameliorated the Incidence of Chronic Hepatitis in Patients with Breast Cancer: A Nationwide Population-Based Cohort Study

We conducted a National Health Insurance Research Database-based Taiwanese nationwide population-based cohort study to evaluate whether Chinese herbal medicine (CHM) treatment decreased the incidence of chronic hepatitis in breast cancer patients receiving chemotherapy and/or radiotherapy. A total of 81171 patients were diagnosed with breast cancer within the defined study period. After randomly equal matching, data from 13856 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence and therapeutic potential of CHM in patients with breast cancer. The patients with breast cancer receiving CHM treatment exhibited a significantly decreased incidence rate of chronic hepatitis even across the stratification of age, CCI score, and treatments. The cumulative incidence of chronic hepatitis for a period of seven years after initial breast cancer diagnosis was also reduced in the patients receiving CHM treatment. The ten most commonly used single herbs and formulas were effective in protecting liver function in patients with breast cancer, where Hedyotis diffusa and Jia-Wei-Xiao-Yao-San were the most commonly used herbal agents. In conclusion, our study provided information that western medicine therapy combined with CHM as an adjuvant modality may have a significant impact on liver protection in patients with breast cancer

The Inhibitory Effect of Ellagic Acid on Cell Growth of Ovarian Carcinoma Cells

Ellagic acid (EA) is able to inhibit the growth of several cancer cells; however, its effect on human ovarian carcinoma cells has not yet been investigated. Ovarian carcinoma ES-2 and PA-1 cells were treated with EA (10~100 μM) and assessed for viability, cell cycle, apoptosis, anoikis, autophagy, and chemosensitivity to doxorubicin and their molecular mechanisms. EA inhibited cell proliferation in a dose- and time-dependent manner by arresting both cell lines at the G1 phase of the cell cycle, which were from elevating p53 and Cip1/p21 and decreasing cyclin D1 and E levels. EA also induced caspase-3-mediated apoptosis by increasing the Bax : Bcl-2 ratio and restored anoikis in both cell lines. The enhancement of apoptosis and/or inhibition of autophagy in these cells by EA assisted the chemotherapy efficacy. The results indicated that EA is a potential novel chemoprevention and treatment assistant agent for human ovarian carcinoma