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We design, implement, and evaluate a technique to identify the source network interface card (NIC) of an IEEE 802.11 frame through passive radio-frequency analysis. This technique, called PARADIS, leverages minute imperfections of transmitter hardware that are acquired at manufacture and are present even in otherwise identical NICs. These imperfections are transmitter-specific and manifest themselves as artifacts of the emitted signals. In PARADIS, we measure differentiating artifacts of individual wireless frames in the modulation domain, apply suitable machine-learning classification tools to achieve significantly higher degrees of NIC identification accuracy than prior best known schemes.We experimentally demonstrate effectiveness of PARADIS in differentiating between more than 130 identical 802.11 NICs with accuracy in excess of 99%. Our results also show that the accuracy of PARADIS is resilient against ambient noise and fluctuations of the wireless channel.Although our implementation deals exclusively with IEEE 802.11, the approach itself is general and will work with any digital modulation scheme. *

Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf −/− astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.Supplemental material is available at http://www.genesdev.org. The self-renewal, differentiative, and proliferative states of tissue stem and progenitor cells are maintained by a variety of well-defined cell fate determinant factors (Keller 2005). Disregulation of such key developmental regulators and acquisition and maintenance of an immature differentiation phenotype are common themes across a broad spectrum of cancer types, including primary brain cancers (Garraway and Sellers 2006). Indeed, a growing body of evidence supports the view that developmental regulators play direct roles in driving aspiring cancer cells toward a malignant phenotype, one that is endowed with stem-like cell properties including robust renewal potential (Beachy et al. 2004). This cellular phenotype, embodied in the cancer stem cell paradigm (Pardal et al. 2003), has been well documented in the highly malignant brain cancer, primary glioblastoma multiforme (GBM) (Galli et al. 2004;Singh et al. 2004). The cellular origins and specific genetic elements involved in the genesis and maintenance of these so-called brain cancer stem cells (BCSCs) remain areas of intensive investigation. Results and Discussion Id4 is overexpressed human GBM, and can drive transformation of murine Ink4a/Arf −/− astrocytesGiven the biological significance of stem cell fate determinants in the regulation of normal self-renewal and differentiation, we hypothesized that the genetic or epigenetic alterations in classical cell fate determinants might cooperate with prototypical oncogenes and tumor suppressor genes to both effect malignant transformation and endow stem cell-like renewal activity in these tumors (Leung et al. 2004;Ligon et al. 2007). We were particularly focused on the expression and functional activity of inhibitor of differentiation 4 (Id4) in GBM given its prominent role in governing neural stem cell (NSC) fate decisions (Yun et al. 2004). Id4 mRNA levels were found to be increased in nine of 15 GBM samples as compared with human normal brain tissue (Supplemental Fig. S1A) and abundant Id4 mRNA and protein levels were detected in five of seven human glioma cell lines (A172, LN229, LN18, U87MG, and T98G) and an immortalized human NSC line (HB1.F3) (Cho et al. 2002), but not in the normal human astrocytes (NHA) (Supplemental Fig. S1B). Tumor ...

The application of computer-aided design and manufacturing techniques is becoming essential in modern metal-forming technology. Thus process modeling for the determination of deformation mechanics has been a major concern in research . In light of these developments, the finite element method--a technique by which an object is decomposed into pieces and treated as isolated, interacting sections--has steadily assumed increased importance. This volume addresses advances in modern metal-forming technology, computer-aided design and engineering, and the finite element method.

Structural phase transformations of silicon during nanoindentation were investigated in detail at the atomic level. The molecular dynamics simulations of nanoindentation on the (100) and (111) surface of single crystalline silicon were simulated, and this supported the theoretical prediction of the anisotropic behaviour of structural phase transformations. Simulations showed that microscopic aspects of phase transformation varied according to the crystallographic orientation of the contact surface and were directly linked to the slip system of silicon. In the transformed region along the centreline, the crystalline structure of Si-II and the amorphous structure were observed when silicon was loaded in the [100] and [111] directions, respectively. Simultaneously, metastable phases with fourfold coordination, such as Si-III and Si-XII, were formed by the inhomogeneous distortion in the slip direction of silicon and observed along the direction. Additionally, our results indicated that the deviatoric stress added to the hydrostatic pressure induced by loading was an indispensable factor for the structural phase transformation to Si-II during nanoindentation on the (100) surface.

Collagen triple helix repeat-containing 1 (CTHRC1) is known to be aberrantly upregulated in most human solid tumors, although the functional roles of CTHRC1 in colorectal cancer remain unclear. In this study, we investigated the occurrence of CTHRC1 upregulation and its role in vivo and in vitro. The expression profile and clinical importance of CTHRC1 were examined by reverse transcription-polymerase chain reaction and immunohistochemical analyses in normal and tumor patient samples. CTHRC1 was detectable in normal tissues, but also was highly expressed in tumor specimens. CTHRC1 upregulation was significantly associated with demethylation of the CTHRC1 promoter in colon cancer cell lines and tumor tissues. Clinicopathologic analyses showed that nodal status and expression of CTHRC1 (95% CI 0.999–3.984, p=0.05) were significant prognostic factors for disease-free survival. Promoter CpG methylation and hypermethylation status were measured by bisulfite sequencing and pyrosequencing analysis. Furthermore, we showed that overexpression of CTHRC1 in the SW480 and HT-29 cell lines increased invasiveness, an effect mediated by extracellular signal-regulated kinase (ERK)-dependent upregulation of matrix metalloproteinase 9 (MMP9). Consistent with this, we found that knockdown of CTHRC1 attenuated ERK activation and cancer cell invasivity. These results demonstrate that CTHRC1 expression is elevated in human colon cancer cell lines and clinical specimens, and promotes cancer cell invasivity through ERK-dependent induction of MMP9 expression. Our results further suggest that high levels of CTHRC1 expression are associated with poor clinical outcomes.

Purpose: Glioblastomas (GBMs), neoplasms derived from glia and neuroglial progenitor cells, are the most common and lethal malignant primary brain tumors diagnosed in adults, with a median survival of 14 months. GBM tumorigenicity is often driven by genetic aberrations in receptor tyrosine kinases, such as amplification and mutation of EGFR. Experimental Design: Using a Drosophila glioma model and human patient–derived GBM stem cells and xenograft models, we genetically and pharmacologically tested whether the YAP and TAZ transcription coactivators, effectors of the Hippo pathway that promote gene expression via TEA domain (TEAD) cofactors, are key drivers of GBM tumorigenicity downstream of oncogenic EGFR signaling. Results: YAP and TAZ are highly expressed in EGFR-amplified/mutant human GBMs, and their knockdown in EGFR-amplified/mutant GBM cells inhibited proliferation and elicited apoptosis. Our results indicate that YAP/TAZ-TEAD directly regulates transcription of SOX2, C-MYC, and EGFR itself to create a feedforward loop to drive survival and proliferation of human GBM cells. Moreover, the benzoporphyrin derivative verteporfin, a disruptor of YAP/TAZ-TEAD–mediated transcription, preferentially induced apoptosis of cultured patient-derived EGFR-amplified/mutant GBM cells, suppressed expression of YAP/TAZ transcriptional targets, including EGFR, and conferred significant survival benefit in an orthotopic xenograft GBM model. Our efforts led us to design and initiate a phase 0 clinical trial of Visudyne, an FDA-approved liposomal formulation of verteporfin, where we used intraoperative fluorescence to observe verteporfin uptake into tumor cells in GBM tumors in human patients. Conclusions: Together, our data suggest that verteporfin is a promising therapeutic agent for EGFR-amplified and -mutant GBM.

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