Design of reconfigurable on-chip wireless interconnections through Optical Phased Arrays.

In this paper we report the design of a device allowing on-chip optical wireless interconnections, based on transmitting and receiving Optical Phased Arrays (OPA). The proposed device aims at realizing high-bandwidth and power-efficient reconfigurable connections between multiple nodes, e.g. chiplets stacked onto a common silicon interposer in 2.5D manycore systems. The communication through an optical wireless switch is a completely novel approach to overcome the bottleneck of wired communication and to provide flexibility in the network topology configuration. We report the OPA design criteria as well as the results of three-dimensional Finite Difference Time Domain (FDTD) simulations. We exploit the in-plane radiation of simple taper antennas to implement 1×N and N × N switching matrices. The effect of the multipath propagation in the on-chip multi-layered medium is also taken into account.

DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1alpha gene locus.

Top1 inhibition by camptothecin (CPT) perturbs RNA polymerase II (Pol II) density at promoters and along transcribed genes suggesting an involvement of Top1 in Pol II pausing. Here, we demonstrate that Top1 inhibition favors Pol II escape from a promoter-proximal pausing site of the human HIF-1alpha gene in living cells. Interestingly, alternative splicing at exon 11 was markedly altered in nascent HIF-1alpha mRNAs, and chromatin structure was also affected with enhanced histone acetylation and reduced nucleosome density in a manner dependent on cdk activity. Moreover, CPT increases transcription of a novel long RNA (5'aHIF1alpha), antisense to human HIF-1alpha mRNA, and a known antisense RNA at the 3'-end of the gene, while decreasing mRNA levels under normoxic and hypoxic conditions. The effects require Top1, but are independent from Top1-induced replicative DNA damage. Chromatin RNA immunoprecipitation results showed that CPT can activate antisense transcription mediated by cyclin-dependent kinase (cdk) activity. Thus, Top1 inhibition can trigger a transcriptional stress, involving antisense transcription and increased chromatin accessibility, which is dependent on cdk activity and deregulated Pol II pausing. A changed balance of antisense transcripts and mRNAs may then lead to altered regulation of HIF-1alpha activity in human cancer cells.

Special Issue on Networks-on-Chip Again on the Rise: From Emerging Applications to Emerging Technologies.

Twenty years after the advent of interconnection networks to tackle the on-chip communication bottleneck [...].

The natural inhibitor of DNA topoisomerase I, camptothecin, modulates HIF-1α activity by changing miR expression patterns in human cancer cells.

DNA topoisomerase I (Top1) inhibition by camptothecin derivatives can impair the hypoxia-induced cell transcriptional response. In the present work, we determined molecular aspects of the mechanism of camptothecin's effects on hypoxia-inducible factor-1α (HIF-1α) activity in human cancer cells. In particular, we provide evidence that low concentrations of camptothecin, without interfering with HIF-1α mRNA levels, can reduce HIF-1α protein expression and activity. As luciferase assays demonstrated the involvement of the HIF-1α mRNA 3' untranslated region in camptothecin-induced impairment of HIF-1α protein regulation, we performed microarray analysis to identify camptothecin-induced modification of microRNAs (miRNA) targeting HIF-1α mRNA under hypoxic-mimetic conditions. The selected miRNAs were then further analyzed, demonstrating a role for miR-17-5p and miR-155 in HIF-1α protein expression after camptothecin treatments. The present findings establish miRNAs as key factors in a molecular pathway connecting Top1 inhibition and human HIF-1α protein regulation and activity, widening the biologic and molecular activity of camptothecin derivatives and the perspective for novel clinical interventions.

Characterization of novel antisense HIF-1α transcripts in human cancers.

Whole transcriptome analyses have revealed new classes of long ncRNA (lncRNA), the functions of which are however largely unknown. Recently, we showed that the antitumor DNA topoisomerase I (Top1) inhibitor camptothecin (CPT) increases the cellular levels of two antisense lncRNAs at the 5' (5'aHIF-1α) and 3' (3'aHIF-1α) ends of the human HIF-1α gene. To gain insights into their functions, we have here determined structural and functional aspects of the two antisense RNAs in human cancer cell lines and kidney tumor specimen. We found that the antisense transcripts are activated in response to partially different kinds of stress, and that the 5'aHIF-1α has a 5'Cap and a poly(A+) tail, while the 3'aHIF-1α is known to lack both modifications. Cell fractionation experiments showed that 5' and 3' antisense RNAs are nuclear transcripts. Further analyses by RNA-FISH showed that the 5'aHIF-1α accumulates at the perinuclear cellular compartment and co-localizes with the nuclear pore complex Nup62 protein, suggesting a role in nuclear membrane trafficking. Finally, we provide evidence that the studied antisense lncRNAs are expressed in human kidney cancer tissues, highlighting their possible roles in cancer development. Altogether, our findings may suggest a novel function of 5'aHIF-1α in membrane transport that may regulate the cancer-relevant HIF-1α pathway.