Helicity at Photospheric and Chromospheric Heights

In the solar atmosphere the twist parameter $\alpha$ has the same sign as magnetic helicity. It has been observed using photospheric vector magnetograms that negative/positive helicity is dominant in the northern/southern hemisphere of the Sun. Chromospheric features show dextral/sinistral dominance in the northern/southern hemisphere and sigmoids observed in X-rays also have a dominant sense of reverse-S/forward-S in the northern/southern hemisphere. It is of interest whether individual features have one-to-one correspondence in terms of helicity at different atmospheric heights. We use UBF \Halpha images from the Dunn Solar Telescope (DST) and other \Halpha data from Udaipur Solar Observatory and Big Bear Solar Observatory. Near-simultaneous vector magnetograms from the DST are used to establish one-to-one correspondence of helicity at photospheric and chromospheric heights. We plan to extend this investigation with more data including coronal intensities.Comment: 5 pages, 1 figure, 1 table To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Distribution of CD133 reveals glioma stem cells self-renew through symmetric and asymmetric cell divisions

Malignant gliomas contain a population of self-renewing tumorigenic stem-like cells; however, it remains unclear how these glioma stem cells (GSCs) self-renew or generate cellular diversity at the single-cell level. Asymmetric cell division is a proposed mechanism to maintain cancer stem cells, yet the modes of cell division that GSCs utilize remain undetermined. Here, we used single-cell analyses to evaluate the cell division behavior of GSCs. Lineage-tracing analysis revealed that the majority of GSCs were generated through expansive symmetric cell division and not through asymmetric cell division. The majority of differentiated progeny was generated through symmetric pro-commitment divisions under expansion conditions and in the absence of growth factors, occurred mainly through asymmetric cell divisions. Mitotic pair analysis detected asymmetric CD133 segregation and not any other GSC marker in a fraction of mitoses, some of which were associated with Numb asymmetry. Under growth factor withdrawal conditions, the proportion of asymmetric CD133 divisions increased, congruent with the increase in asymmetric cell divisions observed in the lineage-tracing studies. Using single-cell-based observation, we provide definitive evidence that GSCs are capable of different modes of cell division and that the generation of cellular diversity occurs mainly through symmetric cell division, not through asymmetric cell division

Strong Casimir force reduction through metallic surface nanostructuring

The Casimir force between bodies in vacuum can be understood as arising from their interaction with an infinite number of fluctuating electromagnetic quantum vacuum modes, resulting in a complex dependence on the shape and material of the interacting objects. Becoming dominant at small separations, the force plays a significant role in nanomechanics and object manipulation at the nanoscale, leading to a considerable interest in identifying structures where the Casimir interaction behaves significantly different from the well-known attractive force between parallel plates. Here we experimentally demonstrate that by nanostructuring one of the interacting metal surfaces at scales below the plasma wavelength, an unexpected regime in the Casimir force can be observed. Replacing a flat surface with a deep metallic lamellar grating with sub-100 nm features strongly suppresses the Casimir force and for large inter-surfaces separations reduces it beyond what would be expected by any existing theoretical prediction.Comment: 11 pages, 8 figure

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

Grp78 promotes the invasion of hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Glucose regulated protein 78 (Grp78) is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism.</p> <p>Methods</p> <p>The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+)-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining.</p> <p>Results</p> <p>Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased RhoA-GTP level, and Grp78 siRNA knockdown rescued RhoA-GTP level in Grp78 overexpressing cells, indicating Grp78 inhibited RhoA activity in hepatocellular carcinoma cells. Furthermore, overexpression of Grp78 in SMMC7721 cells increased phospho-p190RhoGAP level. FAK siRNA knockdown in Grp78 overexpressing cells reversed phospho-p190RhoGAP level. These data suggested that Grp78 inhibited RhoA activity by up-regulated phospho-p190RhoGAP level and Grp78 mediated p190RhoGAP phosphorylation is FAK dependent.</p> <p>Conclusion</p> <p>Grp78 promoted the invasion of hepatocellular carcinoma both in vitro and in vivo. Overexpression of Grp78 in hepatocellular carcinoma cells enhanced the activation and activity of FAK which negatively regulated Rock kinase activity by promoting the phosphorylation of p190RhoGAP.</p

Direct In Vivo Evidence for Tumor Propagation by Glioblastoma Cancer Stem Cells

High-grade gliomas (World Health Organization grade III anaplastic astrocytoma and grade IV glioblastoma multiforme), the most prevalent primary malignant brain tumors, display a cellular hierarchy with self-renewing, tumorigenic cancer stem cells (CSCs) at the apex. While the CSC hypothesis has been an attractive model to describe many aspects of tumor behavior, it remains controversial due to unresolved issues including the use of ex vivo analyses with differential growth conditions. A CSC population has been confirmed in malignant gliomas by preferential tumor formation from cells directly isolated from patient biopsy specimens. However, direct comparison of multiple tumor cell populations with analysis of the resulting phenotypes of each population within a representative tumor environment has not been clearly described. To directly test the relative tumorigenic potential of CSCs and non-stem tumor cells in the same microenvironment, we interrogated matched tumor populations purified from a primary human tumor transplanted into a xenograft mouse model and monitored competitive in vivo tumor growth studies using serial in vivo intravital microscopy. While CSCs were a small minority of the initial transplanted cancer cell population, the CSCs, not the non-stem tumor cells, drove tumor formation and yielded tumors displaying a cellular hierarchy. In the resulting tumors, a fraction of the initial transplanted CSCs maintained expression of stem cell and proliferation markers, which were significantly higher compared to the non-stem tumor cell population and demonstrated that CSCs generated cellular heterogeneity within the tumor. These head-to-head comparisons between matched CSCs and non-stem tumor cells provide the first functional evidence using live imaging that in the same microenvironment, CSCs more than non-stem tumor cells are responsible for tumor propagation, confirming the functional definition of a CSC

The prognostic value of nestin expression in newly diagnosed glioblastoma: Report from the Radiation Therapy Oncology Group

<p>Abstract</p> <p>Background</p> <p>Nestin is an intermediate filament protein that has been implicated in early stages of neuronal lineage commitment. Based on the heterogeneous expression of nestin in GBM and its potential to serve as a marker for a dedifferentiated, and perhaps more aggressive phenotype, the Radiation Therapy Oncology Group (RTOG) sought to determine the prognostic value of nestin expression in newly diagnosed GBM patients treated on prior prospective RTOG clinical trials.</p> <p>Methods</p> <p>Tissue microarrays were prepared from 156 patients enrolled in these trials. These specimens were stained using a mouse monoclonal antibody specific for nestin and expression was measured by computerized quantitative image analysis using the Ariol SL-50 system. The parameters measured included both staining intensity and the relative area of expression within a specimen. This resulted into 3 categories: low, intermediate, and high nestin expression, which was then correlated with clinical outcome.</p> <p>Results</p> <p>A total of 153 of the 156 samples were evaluable for this study. There were no statistically significant differences between pretreatment patient characteristics and nestin expression. There was no statistically significant difference in either overall survival or progression-free survival (PFS) demonstrated, although a trend in decreased PFS was observed with high nestin expression (p = 0.06).</p> <p>Conclusion</p> <p>Although the correlation of nestin expression and histologic grade in glioma is of considerable interest, the presented data does not support its prognostic value in newly diagnosed GBM. Further studies evaluating nestin expression may be more informative when studied in lower grade glioma, in the context of markers more specific to tumor stem cells, and using more recent specimens from patients treated with temozolomide in conjunction with radiation.</p

Quantifying similarity of pore-geometry in nanoporous materials

In most applications of nanoporous materials the pore structure is as important as the chemical composition as a determinant of performance. For example, one can alter performance in applications like carbon capture or methane storage by orders of magnitude by only modifying the pore structure. For these applications it is therefore important to identify the optimal pore geometry and use this information to find similar materials. However, the mathematical language and tools to identify materials with similar pore structures, but different composition, has been lacking. We develop a pore recognition approach to quantify similarity of pore structures and classify them using topological data analysis. This allows us to identify materials with similar pore geometries, and to screen for materials that are similar to given top-performing structures. Using methane storage as a case study, we also show that materials can be divided into topologically distinct classes requiring different optimization strategies

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs.</p> <p>Methods</p> <p>55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated.</p> <p>Results</p> <p>Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact.</p> <p>Conclusions</p> <p>Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs.</p

T Cells Enhance Stem-Like Properties and Conditional Malignancy in Gliomas

Small populations of highly tumorigenic stem-like cells (cancer stem cells; CSCs) can exist within, and uniquely regenerate cancers including malignant brain tumors (gliomas). Many aspects of glioma CSCs (GSCs), however, have been characterized in non-physiological settings.We found gene expression similarity superiorly defined glioma "stemness", and revealed that GSC similarity increased with lower tumor grade. Using this method, we examined stemness in human grade IV gliomas (GBM) before and after dendritic cell (DC) vaccine therapy. This was followed by gene expression, phenotypic and functional analysis of murine GL26 tumors recovered from nude, wild-type, or DC-vaccinated host brains.GSC similarity was specifically increased in post-vaccine GBMs, and correlated best to vaccine-altered gene expression and endogenous anti-tumor T cell activity. GL26 analysis confirmed immune alterations, specific acquisition of stem cell markers, specifically enhanced sensitivity to anti-stem drug (cyclopamine), and enhanced tumorigenicity in wild-type hosts, in tumors in proportion to anti-tumor T cell activity. Nevertheless, vaccine-exposed GL26 cells were no more tumorigenic than parental GL26 in T cell-deficient hosts, though they otherwise appeared similar to GSCs enriched by chemotherapy. Finally, vaccine-exposed GBM and GL26 exhibited relatively homogeneous expression of genes expressed in progenitor cells and/or differentiation.T cell activity represents an inducible physiological process capable of proportionally enriching GSCs in human and mouse gliomas. Stem-like gliomas enriched by strong T cell activity, however, may differ from other GSCs in that their stem-like properties may be disassociated from increased tumor malignancy and heterogeneity under specific host immune conditions