Selective nitrogen adsorption via backbonding in a metal-organic framework with exposed vanadium sites.

Industrial processes prominently feature π-acidic gases, and an adsorbent capable of selectively interacting with these molecules could enable important chemical separations1-4. Biological systems use accessible, reducing metal centres to bind and activate weakly π-acidic species, such as N2, through backbonding interactions5-7, and incorporating analogous moieties into a porous material should give rise to a similar adsorption mechanism for these gaseous substrates8. Here, we report a metal-organic framework featuring exposed vanadium(II) centres capable of back-donating electron density to weak π acids to successfully target π acidity for separation applications. This adsorption mechanism, together with a high concentration of available adsorption sites, results in record N2 capacities and selectivities for the removal of N2 from mixtures with CH4, while further enabling olefin/paraffin separations at elevated temperatures. Ultimately, incorporating such π-basic metal centres into porous materials offers a handle for capturing and activating key molecular species within next-generation adsorbents

Genetic characterization of Gainj- and Kalam-Speaking peoples of Papua New Guinea

The research presented focuses on genetic variation in the Gainj- and Kalam-speaking peoples of highland Papua New Guinea. The primary data are typings at 51 genetic loci observed on 600 individuals who reside in 21 census units, called parishes. These data are augmented by cultural and demographic information that has also been collected. Parish sizes are small, ranging from 20 to about 200 individuals. Direct Western contact with these people has been occuring only for the past three decades. Although Westernization is currently increasing, we find that much of the traditional settlement pattern and mate exchange system is preserved. There are segregating variants at 27 loci. Four rare variants are initially described: NP 4-Kalam, ADA 6-Kalam, PEPA 3-Kalam, and FUM 2-Kalam. We find evidence for a new Gm haplotype, a; —, that is recessive to all other Gm haplotypes. It occurs at a high enough frequency, f(a;—) = 0.119, to be considered a “private polymorphism.” Average per locus heterozygosity is estimated to be 0.053. This value is not statistically different from levels observed on two modern urban populations. Thus, there is no evidence for a reduced level of genetic variation in these people, despite small parish sizes and a relatively unacculturated social structure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37632/1/1330700113_ftp.pd

VIPER: Visualization Pipeline for RNA-seq, a Snakemake workflow for efficient and complete RNA-seq analysis

BACKGROUND: RNA sequencing has become a ubiquitous technology used throughout life sciences as an effective method of measuring RNA abundance quantitatively in tissues and cells. The increase in use of RNA-seq technology has led to the continuous development of new tools for every step of analysis from alignment to downstream pathway analysis. However, effectively using these analysis tools in a scalable and reproducible way can be challenging, especially for non-experts. RESULTS: Using the workflow management system Snakemake we have developed a user friendly, fast, efficient, and comprehensive pipeline for RNA-seq analysis. VIPER (Visualization Pipeline for RNA-seq analysis) is an analysis workflow that combines some of the most popular tools to take RNA-seq analysis from raw sequencing data, through alignment and quality control, into downstream differential expression and pathway analysis. VIPER has been created in a modular fashion to allow for the rapid incorporation of new tools to expand the capabilities. This capacity has already been exploited to include very recently developed tools that explore immune infiltrate and T-cell CDR (Complementarity-Determining Regions) reconstruction abilities. The pipeline has been conveniently packaged such that minimal computational skills are required to download and install the dozens of software packages that VIPER uses. CONCLUSIONS: VIPER is a comprehensive solution that performs most standard RNA-seq analyses quickly and effectively with a built-in capacity for customization and expansion

Transcriptomic analysis of micropapillary high grade T1 urothelial bladder cancer

No consensus currently exist on the optimal treatment of patients with high-risk nonmuscle invasive (HGT1) micropapillary variant of bladder cancer (MPBC). Transcripsome analysis may allow stratification of MPBC-HGT1 enabling prediction of recurrence and guide therapeutic management for individual patients. Whole transcriptome RNA-Sequencing of tumors from 23 patients with MPBC-HGT1 and 64 conventional urothelial carcinomas (cUC) (reference set) was performed. Differentially expressed genes between MPBC-HGT1 and cUC-HGT1 were explored. Cox proportional hazard models and Kapplan-Meier methods were used to assess the relation between time to progression (TTP) and individual gene expression adjusting for clinical covariates. Over 3000 genes were differentially expressed in MPBC-HGT1 as compared with cUC-HGT1 and a 26-gene signature is characteristic of MPBC within HGT1. A set of three genes; CD36, FAPB3 and RAETE1 ; were significantly associated with TTP. High expression of FABP3 and CD36 were associated with shorter TTP (p = 0.045 and p = 0.08) as was low expression of RAET1E (p = 0.01). Our study suggest that a 26-gene signature can define MPBC-HGT1 within conventional urothelial carcinomas. A prognostic risk index of three genes (FABP3, CD36 and RAET1E) was found to be associated with shorter TTP and may help classify a group of patients with MPBC-HGT1 with high-risk of early progression. These observations might have implications in terms of radical cystectomy recommendation in MPBC patients

Phase-Coherent Synthesis of Optical Frequencies and Waveforms

Precision phase control of an ultrawide-bandwidth optical-frequency comb has produced remarkable and unexpected progress in both areas of optical-frequency metrology and ultrafast optics. A frequency comb (with 100 MHz spacing) spanning an entire optical octave (\u3e300 THz) has been produced, corresponding to millions of marks on a frequency “ruler” that are stable at the Hz level. The precision comb has been used to establish a simple optical clock based on an optical transition of iodine molecules, providing an rf clock signal with a frequency stability comparable to that of an optical standard, and which is superior to almost all conventional rf sources. To realize a high-power cw optical frequency synthesizer, a separate, widely tunable single-frequency cw laser has been employed to randomly access the stabilized optical comb and lock to any desired comb component. Carrier-envelope phase stabilization of few-cycle optical pulses has recently been realized. This advance in femtosecond technology is important for both extreme non-linear optics and optical-frequency metrology. With two independent femtosecond lasers, we have not only synchronized their relative pulse timing at the femtosecond level, but have also phase-locked their carrier frequencies, thus establishing phase coherence between the two lasers. By coherently stitching the optical bandwidth together, a “synthesized” pulse has been generated with its 2nd-order autocorrelation signal displaying a shorter width than those of the two “parent” lasers

Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of tumorigenesis, and yet their mechanistic roles remain challenging to characterize. Here, we integrate functional proteomics with lncRNA-interactome profiling to characterize Urothelial Cancer Associated 1 (UCA1), a candidate driver of ovarian cancer development. Reverse phase protein array (RPPA) analysis indicates that UCA1 activates transcription coactivator YAP and its target genes. In vivo RNA antisense purification (iRAP) of UCA1 interacting proteins identified angiomotin (AMOT), a known YAP regulator, as a direct binding partner. Loss-of-function experiments show that AMOT mediates YAP activation by UCA1, as UCA1 enhances the AMOT-YAP interaction to promote YAP dephosphorylation and nuclear translocation. Together, we characterize UCA1 as a lncRNA regulator of Hippo-YAP signaling and highlight the UCA1-AMOT-YAP signaling axis in ovarian cancer development

Anisotropic permeability in deterministic lateral displacement arrays

We uncover anisotropic permeability in microfluidic deterministic lateral displacement (DLD) arrays. A DLD array can achieve high-resolution bimodal size-based separation of microparticles, including bioparticles, such as cells. For an application with a given separation size, correct device operation requires that the flow remains at a fixed angle to the obstacle array. We demonstrate via experiments and lattice-Boltzmann simulations that subtle array design features cause anisotropic permeability. Anisotropic permeability indicates the microfluidic array's intrinsic tendency to induce an undesired lateral pressure gradient. This can cause an inclined flow and therefore local changes in the critical separation size. Thus, particle trajectories can become unpredictable and the device useless for the desired separation task. Anisotropy becomes severe for arrays with unequal axial and lateral gaps between obstacle posts and highly asymmetric post shapes. Furthermore, of the two equivalent array layouts employed with the DLD, the rotated-square layout does not display intrinsic anisotropy. We therefore recommend this layout over the easier-to-implement parallelogram layout. We provide additional guidelines for avoiding adverse effects of anisotropy on the DLD.Comment: 13 pages, 10 figures, 1 table, DLD, particle separation, microfluidics, anisotropic permeabilit

Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression

Down syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations with transcriptome changes, we performed paired exogenous spike-in normalized RNA and chromatin immunoprecipitation sequencing in DS models. Absolute normalization unmasks global amplification of gene expression associated with trisomy 21. Overexpression of the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulates transcriptional changes seen with triplication of a Down syndrome critical region on distal chromosome 21, and HMGN1 is necessary for B cell phenotypes in DS models. Absolute exogenous-normalized chromatin immunoprecipitation sequencing (ChIP-Rx) also reveals a global increase in histone H3K27 acetylation caused by HMGN1. Transcriptional amplification downstream of HMGN1 is enriched for stage-specific programs of B cells and B cell acute lymphoblastic leukemia, dependent on the developmental cellular context. These data offer a mechanistic explanation for DS transcriptional patterns and suggest that further study of HMGN1 and RNA amplification in diverse DS phenotypes is warranted. How trisomy 21 contributes to Down syndrome phenotypes, including increased leukemia risk, is not well understood. Mowery et al. use per-cell normalization approaches to reveal global transcriptional amplification in Down syndrome models. HMGN1 overexpression is sufficient to induce these alterations and promotes lineage-associated transcriptional programs, signaling, and B cell progenitor phenotypes