XScan: An Integrated Tool for Understanding Open Source Community-Based Scientific Code

Many scientific communities have adopted community-based models that integrate multiple components to simulate whole system dynamics. The community software projects’ complexity, stems from the integration of multiple individual software components that were developed under different application requirements and various machine architectures, has become a challenge for effective software system understanding and continuous software development. The paper presents an integrated software toolkit called X-ray Software Scanner (in abbreviation, XScan) for a better understanding of large-scale community-based scientific codes. Our software tool provides support to quickly summarize the overall information of scientific codes, including the number of lines of code, programming languages, external library dependencies, as well as architecture-dependent parallel software features. The XScan toolkit also realizes a static software analysis component to collect detailed structural information and provides an interactive visualization and analysis of the functions. We use a large-scale community-based Earth System Model to demonstrate the workflow, functions and visualization of the toolkit. We also discuss the application of advanced graph analytics techniques to assist software modular design and component refactoring

Nanopore-facilitated single molecule detection of circulating microRNAs in cancer patients

Developing new technologies for cancer screening and early diagnosis is a critical issue for saving cancer patients' lives. MicroRNAs (miRNAs) are a class of short (~18-24-nt) non-coding RNAs molecules that regulate gene expression at the post-transcriptional level. Aberrant expression of miRNAs has been found in all types of tumors. Thus miRNAs have been recognized as potential cancer biomarkers. Most notably, specific miRNAs are released from the primary tumor into blood circulation, making the detection of circulating miRNAs profile a powerful tool for noninvasive cancer detection, diagnosis, staging, and monitoring. We developed a robust nanopore sensor that selectively detects single molecules of circulating miRNAs derived from primary cancer. The nanopore is a fabricated 2-nm molecular pore. Such a tiny pore can generate a signature current signal when a miRNA molecule is specifically captured in it. These signals function as fingerprints that enable us to identify a specific miRNA and quantify its concentration. The prototype of nanopore sensor has demonstrated the capability to discriminate single nucleotide difference between miRNAs (single nucleotide polymorphisms, SNPs). In clinical tests, the nanopore has shown the power to differentiate miRNA levels in blood from lung cancer patients and healthy people. Due to the label-free single molecule detection without nucleic acids amplification, the nanopore sensor is higher selective, precise and accurate over the gold standard RT-PCR and microarray. This noninvasive clinical test requires a mere 5 ml of peripheral blood, with a reduced cost from several hundred dollars today to less than 20 dollars per sample. The developing nanopore array would give a high throughput capability for detecting miRNA profile. If validated in clinical trial, the nanopore sensor will become a system available to monitor cancer patients and to screen high risk populations for early diagnosis of cancers which will potentially save the lives of millions. Potential Areas of Applications: * Detection of microRNAs, study of DNA, RNA, DNA/RNA hybrid unzipping kinetics * Study of miRNA mechanism and principle of regulation * Drug discovery and development * Biomarker characterization * Diagnostics and prognostics

Growth diagram of La0.7Sr0.3MnO3 thin films using pulsed laser deposition

An experimental study was conducted on controlling the growth mode of La0.7Sr0.3MnO3 thin films on SrTiO3 substrates using pulsed laser deposition (PLD) by tuning growth temperature, pressure and laser fluence. Different thin film morphology, crystallinity and stoichiometry have been observed depending on growth parameters. To understand the microscopic origin, the adatom nucleation, step advance processes and their relationship to film growth were theoretically analyzed and a growth diagram was constructed. Three boundaries between highly and poorly crystallized growth, 2D and 3D growth, stoichiometric and non-stoichiometric growth were identified in the growth diagram. A good fit of our experimental observation with the growth diagram was found. This case study demonstrates that a more comprehensive understanding of the growth mode in PLD is possible

Persistent androgen receptor-mediated transcription in castration-resistant prostate cancer under androgen-deprived conditions

The androgen receptor (AR) is a ligand-inducible transcription factor that mediates androgen action in target tissues. Upon ligand binding, the AR binds to thousands of genomic loci and activates a cell-type specific gene program. Prostate cancer growth and progression depend on androgen-induced AR signaling. Treatment of advanced prostate cancer through medical or surgical castration leads to initial response and durable remission, but resistance inevitably develops. In castration-resistant prostate cancer (CRPC), AR activity remains critical for tumor growth despite androgen deprivation. Although previous studies have focused on ligand-dependent AR signaling, in this study we explore AR function under the androgen-deprived conditions characteristic of CRPC. Our data demonstrate that AR persistently occupies a distinct set of genomic loci after androgen deprivation in CRPC. These androgen-independent AR occupied regions have constitutively open chromatin structures that lack the canonical androgen response element and are independent of FoxA1, a transcription factor involved in ligand-dependent AR targeting. Many AR binding events occur at proximal promoters, which can act as enhancers to augment transcriptional activities of other promoters through DNA looping. We further show that androgen-independent AR binding directs a gene expression program in CRPC, which is necessary for the growth of CRPC after androgen withdrawal