367 research outputs found

    On the Symmetry Foundation of Double Soft Theorems

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    Double-soft theorems, like its single-soft counterparts, arises from the underlying symmetry principles that constrain the interactions of massless particles. While single soft theorems can be derived in a non-perturbative fashion by employing current algebras, recent attempts of extending such an approach to known double soft theorems has been met with difficulties. In this work, we have traced the difficulty to two inequivalent expansion schemes, depending on whether the soft limit is taken asymmetrically or symmetrically, which we denote as type A and B respectively. We show that soft-behaviour for type A scheme can simply be derived from single soft theorems, and are thus non-preturbatively protected. For type B, the information of the four-point vertex is required to determine the corresponding soft theorems, and thus are in general not protected. This argument can be readily extended to general multi-soft theorems. We also ask whether unitarity can be emergent from locality together with the two kinds of soft theorems, which has not been fully investigated before.Comment: 45 pages, 7 figure

    Metastatic carcinoma of the urinary bladder in a 67-year-old female with underlying triple primary cancers

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    AbstractDue to progressive ageing of our population and increasing cancer incidence rates, more and more patients are presenting with multiple primary cancers. Here we describe a case of metastatic carcinoma involving the urinary bladder with underlying triple primary adenocarcinoma in a female adult.A 67-year-old Taiwanese female presented to our institution in November 1997 with gastric signet ring cell carcinoma, pT2N0M0, status post subtotal gastrectomy. In February 2003 she was diagnosed with left breast invasive lobular carcinoma status post modified radical mastectomy, pT2N2M0. Further examination in January 2005 revealed proximal transverse colon cancer, Dukes' C2, with status post right hemicolectomy. She achieved disease-free status from all three malignancies after surgical resection and adjuvant chemotherapy for breast and colon cancers sequentially. In November 2011, she complained about sudden onset of gross hematuria for several days. Diagnostic cystoscopy showed a mass lesion over her urinary bladder. Cystoscope-assisted biopsy showed metastatic poorly differentiated adenocarcinoma with signet ring appearance. Herein we have discussed the pathologic role in the diagnosis of metastatic tumor involving a patient with multiple primary cancers. We also explored the epidemiologic risk and potential causal mechanism of patients with multiple primary cancers

    Fibronectin and laminin promote differentiation of human mesenchymal stem cells into insulin producing cells through activating Akt and ERK

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    <p>Abstract</p> <p>Background</p> <p>Islet transplantation provides a promising cure for Type 1 diabetes; however it is limited by a shortage of pancreas donors. Bone marrow-derived multipotent mesenchymal stem cells (MSCs) offer renewable cells for generating insulin-producing cells (IPCs).</p> <p>Methods</p> <p>We used a four-stage differentiation protocol, containing neuronal differentiation and IPC-conversion stages, and combined with pellet suspension culture to induce IPC differentiation.</p> <p>Results</p> <p>Here, we report adding extracellular matrix proteins (ECM) such as fibronectin (FN) or laminin (LAM) enhances pancreatic differentiation with increases in insulin and Glut2 gene expressions, proinsulin and insulin protein levels, and insulin release in response to elevated glucose concentration. Adding FN or LAM induced activation of Akt and ERK. Blocking Akt or ERK by adding LY294002 (PI3K specific inhibitor), PD98059 (MEK specific inhibitor) or knocking down Akt or ERK failed to abrogate FN or LAM-induced enhancement of IPC differentiation. Only blocking both of Akt and ERK or knocking down Akt and ERK inhibited the enhancement of IPC differentiation by adding ECM.</p> <p>Conclusions</p> <p>These data prove IPC differentiation by MSCs can be modulated by adding ECM, and these stimulatory effects were mediated through activation of Akt and ERK pathways.</p

    Comparison and Identification of Estrogen-Receptor Related Gene Expression Profiles in Breast Cancer of Different Ethnic Origins

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    The interactions between genetic variants in estrogen receptor (ER) have been identified to be associated with an increased risk of breast cancer. Available evidence indicates that genetic variance within a population plays a crucial role in the occurrence of breast cancer. Thus, the comparison and identification of ER-related gene expression profiles in breast cancer of different ethnic origins could be useful for the development of genetic variant cancer therapy. In this study, we performed microarray experiment to measure the gene expression profiles of 59 Taiwanese breast cancer patients; and through comparative bioinformatics analysis against published U.K. datasets, we revealed estrogen-receptor (ER) related gene expression between Taiwanese and British patients. In addition, SNP databases and statistical analysis were used to elucidate the SNPs associated with ER status. Our microarray results indicate that the expression pattern of the 65 genes in ER+ patients was dissimilar from that of the ER- patients. Seventeen mutually exclusive genes in ER-related breast cancer of the two populations with more than one statistically significant SNP in genotype and allele frequency were identified. These 17 genes and their related SNPs may be important in population-specific ER regulation of breast cancer. This study provides a global and feasible approach to study population-unique SNPs in breast cancer of different ethnic origins

    A comprehensive functional map of the hepatitis C virus genome provides a resource for probing viral proteins.

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    UnlabelledPairing high-throughput sequencing technologies with high-throughput mutagenesis enables genome-wide investigations of pathogenic organisms. Knowledge of the specific functions of protein domains encoded by the genome of the hepatitis C virus (HCV), a major human pathogen that contributes to liver disease worldwide, remains limited to insight from small-scale studies. To enhance the capabilities of HCV researchers, we have obtained a high-resolution functional map of the entire viral genome by combining transposon-based insertional mutagenesis with next-generation sequencing. We generated a library of 8,398 mutagenized HCV clones, each containing one 15-nucleotide sequence inserted at a unique genomic position. We passaged this library in hepatic cells, recovered virus pools, and simultaneously assayed the abundance of mutant viruses in each pool by next-generation sequencing. To illustrate the validity of the functional profile, we compared the genetic footprints of viral proteins with previously solved protein structures. Moreover, we show the utility of these genetic footprints in the identification of candidate regions for epitope tag insertion. In a second application, we screened the genetic footprints for phenotypes that reflected defects in later steps of the viral life cycle. We confirmed that viruses with insertions in a region of the nonstructural protein NS4B had a defect in infectivity while maintaining genome replication. Overall, our genome-wide HCV mutant library and the genetic footprints obtained by high-resolution profiling represent valuable new resources for the research community that can direct the attention of investigators toward unidentified roles of individual protein domains.ImportanceOur insertional mutagenesis library provides a resource that illustrates the effects of relatively small insertions on local protein structure and HCV viability. We have also generated complementary resources, including a website (http://hangfei.bol.ucla.edu) and a panel of epitope-tagged mutant viruses that should enhance the research capabilities of investigators studying HCV. Researchers can now detect epitope-tagged viral proteins by established antibodies, which will allow biochemical studies of HCV proteins for which antibodies are not readily available. Furthermore, researchers can now quickly look up genotype-phenotype relationships and base further mechanistic studies on the residue-by-residue information from the functional profile. More broadly, this approach offers a general strategy for the systematic functional characterization of viruses on the genome scale

    Induced pluripotent stem cells and regenerative medicine

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    AbstractStem cells, a special subset of cells derived from embryo or adult tissues, are known to present the characteristics of self-renewal, multiple lineages of differentiation, high plastic capability, and long-term maintenance. Recent reports have further suggested that neural stem cells (NSCs) derived from the adult hippocampal and subventricular regions possess the utilizing potential to develop the transplantation strategies and to screen the candidate agents for neurogenesis, neuroprotection, and neuroplasticity in neurodegenerative diseases. In this article, we review the roles of NSCs and other stem cells in neuroprotective and neurorestorative therapies for neurological and psychiatric diseases. We show the evidences that NSCs play the key roles involved in the pathogenesis of several neurodegenerative disorders, including depression, stroke, and Parkinson’s disease. Moreover, the potential and possible utilities of induced pluripotent stem cells, reprogramming from adult fibroblasts with ectopic expression of four embryonic genes, are also reviewed and further discussed. An understanding of the biophysiology of stem cells could help us elucidate the pathogenicity and develop new treatments for neurodegenerative disorders. In contrast to cell transplantation therapies, the application of stem cells can further provide a platform for drug discovery and small molecular testing, including Chinese herbal medicines. In addition, the high-throughput stem cell-based systems can be used to elucidate the mechanisms of neuroprotective candidates in translation medical research for neurodegenerative diseases

    The Equatorial El Niño-Southern Oscillation Signatures Observed by FORMOSAT-3/COSMIC from July 2006 to January 2012

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    This paper uses the tropospheric pressure, temperature, and water vapor pressure observed by six micro-satellites of the FORMOSAT-3/COSMIC (F3/C) constellation to study El Niño-Southern Oscillation (ENSO) events from July 2006 to January 2012. The temperature and pressure profiles are used to derive the height, pressure, temperature, and potential temperature of the lapse rate tropopause. Following the calculation of the standard normalized Southern Oscillation Index (SOI) and the Niño 3.4 index, the corresponding indices of the four tropopause parameters are derived. Good agreements between the standard and F3/C-derived indices show that the derived indices are significant for monitoring ENSO signatures. With the uniform coverage, the global F3/C profiles are used to construct three-dimensional structures of temperature, pressure, and water vapor pressure to gain a better understanding of tropospheric structures and dynamics during the ENSO events
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