Effect of Sparse-Build Internal Structure on Performance of Fused Deposition Modeling Tools under Pressure

Two different approaches to design a sparse-build tool for fabrication by the fused deposition modeling (FDM) process are compared. One approach uses a 2D lattice structure and the other approach is inspired by topology optimization. Ultem 9085 is used as the material, and the amount of material used to build the tool is kept constant to ensure a fair comparison. A solid tool is also included in the comparison. The performance of the tool under uniform pressure is simulated using finite element analysis (FEA) and the accuracy of the FEA results is verified by comparing them with experimentally measured data for a similar tool. The build material, support material, build time, maximum displacement, and maximum von Mises stress are compared for the three build approaches, with an emphasis on the pros and cons of each sparsebuild tool with regards to performance under uniform pressure and fabrication by FDM

Is sex necessary?

Fungal sexual reproductive modes have markedly high diversity and plasticity, and asexual species have been hypothesized to arise frequently from sexual fungal species. A recent study on the red yeasts provides further support for the notion that sexual ancestors may give rise to shorter-lived asexual species. However, presumed asexual species may also be cryptically sexual, as revealed by other recent studies

Security and Privacy Issues in Wireless Mesh Networks: A Survey

This book chapter identifies various security threats in wireless mesh network (WMN). Keeping in mind the critical requirement of security and user privacy in WMNs, this chapter provides a comprehensive overview of various possible attacks on different layers of the communication protocol stack for WMNs and their corresponding defense mechanisms. First, it identifies the security vulnerabilities in the physical, link, network, transport, application layers. Furthermore, various possible attacks on the key management protocols, user authentication and access control protocols, and user privacy preservation protocols are presented. After enumerating various possible attacks, the chapter provides a detailed discussion on various existing security mechanisms and protocols to defend against and wherever possible prevent the possible attacks. Comparative analyses are also presented on the security schemes with regards to the cryptographic schemes used, key management strategies deployed, use of any trusted third party, computation and communication overhead involved etc. The chapter then presents a brief discussion on various trust management approaches for WMNs since trust and reputation-based schemes are increasingly becoming popular for enforcing security in wireless networks. A number of open problems in security and privacy issues for WMNs are subsequently discussed before the chapter is finally concluded.Comment: 62 pages, 12 figures, 6 tables. This chapter is an extension of the author's previous submission in arXiv submission: arXiv:1102.1226. There are some text overlaps with the previous submissio

Dynamics of Metal Centers Monitored by Nuclear Inelastic Scattering

Nuclear inelastic scattering of synchrotron radiation has been used now since 10 years as a tool for vibrational spectroscopy. This method has turned out especially useful in case of large molecules that contain a M\"ossbauer active metal center. Recent applications to iron-sulfur proteins, to iron(II) spin crossover complexes and to tin-DNA complexes are discussed. Special emphasis is given to the combination of nuclear inelastic scattering and density functional calculations

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

A 3D Model of the Membrane Protein Complex Formed by the White Spot Syndrome Virus Structural Proteins

Outbreaks of white spot disease have had a large negative economic impact on cultured shrimp worldwide. However, the pathogenesis of the causative virus, WSSV (whit spot syndrome virus), is not yet well understood. WSSV is a large enveloped virus. The WSSV virion has three structural layers surrounding its core DNA: an outer envelope, a tegument and a nucleocapsid. In this study, we investigated the protein-protein interactions of the major WSSV structural proteins, including several envelope and tegument proteins that are known to be involved in the infection process.In the present report, we used coimmunoprecipitation and yeast two-hybrid assays to elucidate and/or confirm all the interactions that occur among the WSSV structural (envelope and tegument) proteins VP51A, VP19, VP24, VP26 and VP28. We found that VP51A interacted directly not only with VP26 but also with VP19 and VP24. VP51A, VP19 and VP24 were also shown to have an affinity for self-interaction. Chemical cross-linking assays showed that these three self-interacting proteins could occur as dimers.From our present results in conjunction with other previously established interactions we construct a 3D model in which VP24 acts as a core protein that directly associates with VP26, VP28, VP38A, VP51A and WSV010 to form a membrane-associated protein complex. VP19 and VP37 are attached to this complex via association with VP51A and VP28, respectively. Through the VP26-VP51C interaction this envelope complex is anchored to the nucleocapsid, which is made of layers of rings formed by VP664. A 3D model of the nucleocapsid and the surrounding outer membrane is presented

BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disease that kills ~50% of adult patients. With the exception of some BCR-ABL1(+) patients who benefit from tyrosine kinase inhibitors, there are no effective targeted therapies for adult B-ALL patients and chemotherapy remains first-line therapy despite adverse side effects and poor efficacy. We show that, although the MEK/ERK pathway is activated in B-ALL cells driven by different oncogenes, MEK inhibition does not suppress B-ALL cell growth. However, MEK inhibition synergized with BCL-2/BCL-XL family inhibitors to suppress proliferation and induce apoptosis in B-ALL cells. We show that this synergism is mediated by the pro-apoptotic factor BIM, which is dephosphorylated as a result of MEK inhibition, allowing it to bind to and neutralize MCL-1, thereby enhancing BCL-2/BCL-XL inhibitor-induced cell death. This cooperative effect is observed in B-ALL cells driven by a range of genetic abnormalities and therefore has significant therapeutic potential

Simultaneous CXCL12 and ESR1 CpG island hypermethylation correlates with poor prognosis in sporadic breast cancer

<p>Abstract</p> <p>Background</p> <p>CXCL12 is a chemokine that is constitutively expressed in many organs and tissues. <it>CXCL12 </it>promoter hypermethylation has been detected in primary breast tumours and contributes to their metastatic potential. It has been shown that the oestrogen receptor α (<it>ESR1</it>) gene can also be silenced by DNA methylation. In this study, we used methylation-specific PCR (MSP) to analyse the methylation status in two regions of the <it>CXCL12 </it>promoter and <it>ESR1 </it>in tumour cell lines and in primary breast tumour samples, and correlated our results with clinicopathological data.</p> <p>Methods</p> <p>First, we analysed <it>CXCL12 </it>expression in breast tumour cell lines by RT-PCR. We also used 5-aza-2'-deoxycytidine (5-aza-CdR) treatment and DNA bisulphite sequencing to study the promoter methylation for a specific region of <it>CXCL12 </it>in breast tumour cell lines. We evaluated <it>CXCL12 </it>and <it>ESR1 </it>methylation in primary tumour samples by methylation-specific PCR (MSP). Finally, promoter hypermethylation of these genes was analysed using Fisher's exact test and correlated with clinicopathological data using the Chi square test, Kaplan-Meier survival analysis and Cox regression analysis.</p> <p>Results</p> <p><it>CXCL12 </it>promoter hypermethylation in the first region (island 2) and second region (island 4) was correlated with lack of expression of the gene in tumour cell lines. In the primary tumours, island 2 was hypermethylated in 14.5% of the samples and island 4 was hypermethylated in 54% of the samples. The <it>ESR1 </it>promoter was hypermethylated in 41% of breast tumour samples. In addition, the levels of ERα protein expression diminished with increased frequency of <it>ESR1 </it>methylation (p < 0.0001). This study also demonstrated that <it>CXCL12 </it>island 4 and <it>ESR1 </it>methylation occur simultaneously at a high frequency (p = 0.0220).</p> <p>Conclusions</p> <p>This is the first study showing a simultaneous involvement of epigenetic regulation for both <it>CXCL12 </it>and <it>ESR1 </it>genes in Brazilian women. The methylation status of both genes was significantly correlated with histologically advanced disease, the presence of metastases and death. Therefore, the methylation pattern of these genes could be used as a molecular marker for the prediction of breast cancer outcome.</p