Threshold Effects in the Decay of Heavy b' and t' Quarks

A sequential fourth generation is still viable, but the t' and b' quarks are constrained to be not too far apart in mass. The t'{\to}bW and b'{\to}tW decay channels are still being pursued at the Tevatron, which would soon be surpassed by the LHC. We use a convolution method with up to five-body final state to study t' and b' decays. We show how the two decay branches for m_{b'} below the tW threshold, b'{\to}tW^* and t^*W, merge with b'{\to}tW above the threshold. We then consider the heavy-to-heavy transitions b'{\to}t^{\prime(*)}W^{(*)} (or t'{\to}b^{\prime(*)}W^{(*)}), as they are not suppressed by quark mixing. We find that, because of the threshold sensitivity of the branching fraction of t'{\to}b'W^* (or b'{\to}t'W^*), it is possible to measure the strength of the CKM mixing element V_{t'b} (or V_{tb'}), especially when it is rather small. We urge the experiments to pursue and separate the t'{\to}b'W^* (or b'{\to}t'W^*) decay in their search program

Growth factor receptor-Src-mediated suppression of GRK6 dysregulates CXCR4 signaling and promotes medulloblastoma migration

BACKGROUND: Metastasis in medulloblastoma (MB) is associated with poor survival. Recent genetic studies revealed MB to comprise distinct molecular subgroups, including the sonic hedgehog (SHH) subgroup that exhibits a relatively high rate of progression. To identify targeted therapeutics against metastasis, a better understanding of the regulation of MB cell migration is needed. G protein-coupled receptor kinases (GRKs) have been implicated in cancer metastasis through their regulation of G-protein coupled receptors (GPCRs) involved in growth factor (GF)-mediated cell migration. However, the specific roles and regulation of GRKs in MB have not been investigated. METHODS: Microarray mRNA analysis was performed for GRKs, GPCRs, and GFs in 29 human MB, and real time RT-PCR was used to detect GRK6 expression in MB cells. Lenti- or retro-virus infection, and siRNA or shRNA transfection, of MB cells was used to overexpress and knockdown target genes, respectively. Western blot was used to confirm altered expression of proteins. The effect of altered target protein on cell migration was determined by Boyden chamber assay and xCELLigence migration assays. RESULTS: We observed co-overexpression of PDGFRA, CXCR4, and CXCL12 in the SHH MB subtype compared to non-SHH MB (5, 7, and 5-fold higher, respectively). GRK6, which typically acts as a negative regulator of CXCR4 signaling, is downregulated in MB, relative to other GRKs, while the percentage of GRK6 expression is lower in MB tumors with metastasis (22%), compared to those without metastasis (43%). In SHH-responsive MB cells, functional blockade of PDGFR abolished CXCR4-mediated signaling. shPDGFR transfected MB cells demonstrated increased GRK6 expression, while PDGF or 10% FBS treatment of native MB cells reduced the stability of GRK6 by inducing its proteosomal degradation. Overexpression or downregulation of Src, a key mediator of GF receptor/PDGFR signaling, similarly inhibited or induced GRK6 expression, respectively. siRNA downregulation of GRK6 enhanced CXCR4 signaling and promoted MB migration, while lentiviral-GRK6 overexpression suppressed CXCR4 signaling, potentiated the effect of AMD3100, a CXCR4 antagonist, and impaired migration. CONCLUSIONS: Our findings demonstrate a novel mechanism of GF receptor/PDGFR-Src-mediated dysregulation of CXCR4 signaling that promotes MB cell migration, which could potentially be exploited for therapeutic targeting in SHH MB

Incidence Rates of Enterovirus 71 Infections in Young Children during a Nationwide Epidemic in Taiwan, 2008–09

Enterovirus 71 (EV71) was first isolated in California, USA, in 1969. Since then, EV71 has been identified globally. Recently, EV71 caused several life-threatening outbreaks in young children in tropical Asia. Development of EV71 vaccines becomes national priority in several Asia countries including Taiwan. To design clinical trials of EV71 vaccines, age-specific incidence rates of EV71 infections are required to identify target populations, estimate disease burdens, select endpoints of clinical efficacy, and estimate sample size. In Taiwan, nationwide EV71 epidemics occurred every 3–4 years but age-specific incidences of EV71 infection are not available. In 2006, we initiated a prospective cohort study in northern Taiwan to recruit neonates and follow up them. In 2008–09, a nationwide EV71 epidemic occurred and we found that age-specific incidence rates of EV71 infection increased from 1.71 per 100 person-years at 0–6 months of age to 4.09, 5.74, and 4.97 per 100 person-years at 7–12, 13–24, and 25–36 months of age, respectively. The cumulative incidence rate was 15% by 36 months of age, and 29% of EV71 infections were asymptomatic in young children. These findings would be helpful to development of EV71 vaccines in Taiwan and other Asian tropical countries

RSC96 Schwann Cell Proliferation and Survival Induced by Dilong through PI3K/Akt Signaling Mediated by IGF-I

Schwann cell proliferation is critical for the regeneration of injured nerves. Dilongs are widely used in Chinese herbal medicine to remove stasis and stimulate wound-healing functions. Exactly how this Chinese herbal medicine promotes tissue survival remains unclear. The aim of the present study was to investigate the molecular mechanisms by which Dilong promote neuron regeneration. Our results show that treatment with extract of Dilong induces the phosphorylation of the insulin-like growth factor-I (IGF-I)-mediated phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) pathway, and activates protein expression of cell nuclear antigen (PCNA) in a time-dependent manner. Cell cycle analysis showed that G1 transits into the S phase in 12–16 h, and S transits into the G2 phase 20 h after exposure to earthworm extract. Strong expression of cyclin D1, cyclin E and cyclin A occurs in a time-dependent manner. Small interfering RNA (siRNA)-mediated knockdown of PI3K significantly reduced PI3K protein expression levels, resulting in Bcl2 survival factor reduction and a marked blockage of G1 to S transition in proliferating cells. These results demonstrate that Dilong promotes the proliferation and survival of RSC96 cells via IGF-I signaling. The mechanism is mainly dependent on the PI3K protein

Back-Side Wafer Grinding Quality Affecting Back-End Assembly Process for LCD Driver ICs

ABSTRACT Die size and thickness of IC substrate typically vary as a result of the various market demands while the semiconductor process and the product applications develop fast. In order to satisfy the market concerns, the improvement of wafer grinding and dicing saw technology is necessary to provide lighter, thinner and more reliable ICs. Generally, most of previous commercial ICs almost demonstrate the square profile, but some special applications such as liquid-crystaldisplay (LCD) driver ICs request approximate rectangle shape. Furthermore, the ratios of length / width of these drivers are near 14:1, therefore, it is easy to be broken during IC assembly process and induce some reliability defects. However, the growth rate of digital panel displays is gradually increased. This global market is more and more impressed. In this study, how to promote the die strength and investigate the wafer grinding process for the previous LCD products is the main target. Through the analysis of data collection in die sizes, the suitable wafer grinding process is recommended in assembly line and some predictable trends for future panel IC applications are also exposed

Pretreatment with a Heat-Killed Probiotic Modulates the NLRP3 Inflammasome and Attenuates Colitis-Associated Colorectal Cancer in Mice.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Inflammation contributes to cancer development and inflammatory bowel disease is an important risk factor for CRC. The aim of this study is to assess whether a widely used probiotic Enterococcus faecalis can modulate the NLRP3 inflammasome and protect against colitis and colitis-associated CRC. We studied the effect of heat-killed cells of E. faecalis on NLRP3 inflammasome activation in THP-1-derived macrophages. Pretreatment of E. faecalis or NLRP3 siRNA can inhibit NLRP3 inflammasome activation in macrophages in response to fecal content or commensal microbes, P. mirabilis or E. coli, according to the reduction of caspase-1 activation and IL-1β maturation. Mechanistically, E. faecalis attenuates the phagocytosis that is required for the full activation of the NLRP3 inflammasome. In in vivo mouse experiments, E. faecalis can ameliorate the severity of intestinal inflammation and thereby protect mice from dextran sodium sulfate (DSS)-induced colitis and the formation of CRC in wild type mice. On the other hand, E. faecalis cannot prevent DSS-induced colitis in NLRP3 knockout mice. Our findings indicate that application of the inactivated probiotic, E. faecalis, may be a useful and safe strategy for attenuation of NLRP3-mediated colitis and inflammation-associated colon carcinogenesis

Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma

Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and hormonal therapies. Previous studies have shown over-expression of EGFR is associated with high grade tumors and a worse prognosis. Recent studies suggest anticancer therapies targeting the EGFR pathway have shown promising results in clinical trials of RCC patients. Therefore, characterization of the level and localization of EGFR expression in RCC is important for target-dependent therapy. In this study, we investigated the clinical significance of cellular localization of EGFR in human normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63 patients were obtained for characterization of EGFR expression. EGFR protein expression was assessed by immunohistochemistry on a scale from 0 to 300 (percentage of positive cells × staining intensity) and Western blotting. EGFR membranous staining was significantly stronger in RCC tumors than in normal tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly higher in normal than in tumor tissues (P < 0.001). The levels of membranous or cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor grade, TNM stage or overall survival (P > 0.05). These results showed abundant expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR in normal tissues. EGFR expression in RCC was mostly located in the cell membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in cytoplasm. Our results suggest different locations of EGFR expression may be associated with human renal tumorigenesis