Novel CMOS RFIC Layout Generation with Concurrent Device Placement and Fixed-Length Microstrip Routing

With advancing process technologies and booming IoT markets, millimeter-wave CMOS RFICs have been widely developed in re- cent years. Since the performance of CMOS RFICs is very sensi- tive to the precision of the layout, precise placement of devices and precisely matched microstrip lengths to given values have been a labor-intensive and time-consuming task, and thus become a major bottleneck for time to market. This paper introduces a progressive integer-linear-programming-based method to gener- ate high-quality RFIC layouts satisfying very stringent routing requirements of microstrip lines, including spacing/non-crossing rules, precise length, and bend number minimization, within a given layout area. The resulting RFIC layouts excel in both per- formance and area with much fewer bends compared with the simulation-tuning based manual layout, while the layout gener- ation time is significantly reduced from weeks to half an hour.Comment: ACM/IEEE Design Automation Conference (DAC), 201

Polygenic risk scores for prediction of breast cancer risk in Asian populations.

PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30-to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 x 10(-31)).Peer reviewe

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10)

CustomTopo: A topology generation method for application-specific wavelength-routed optical NoCs

Optical network-on-chip (NoC) is a promising platform beyond electronic NoCs. In particular, wavelength-routed optical network-on-chip (WRONoC) is renowned for its high bandwidth and ultra-low signal delay. Current WRONoC topology generation approaches focus on full-connectivity, i.e. all masters are connected to all slaves. This assumption leads to wasted resources for application-specific designs. In this work, we propose CustomTopo: a general solution to the topology generation problem on WRONoCs that supports customized connectivity. CustomTopo models the topology structure and its communication behavior as an integer-linear-programming (ILP) problem, with an adjustable optimization target considering the number of add-drop filters (ADFs), the number of wavelengths, and insertion loss. The time for solving the ILP problem in general positively correlates with the network communication densities. Experimental results show that CustomTopo is applicable for various communication requirements, and the resulting customized topology enables a remarkable reduction in both resource usage and insertion loss