Classical Quantum Friction at Water-Carbon Interfaces.

Friction at water-carbon interfaces remains a major puzzle with theories and simulations unable to explain experimental trends in nanoscale waterflow. A recent theoretical framework─quantum friction (QF)─proposes to resolve these experimental observations by considering nonadiabatic coupling between dielectric fluctuations in water and graphitic surfaces. Here, using a classical model that enables fine-tuning of the solid's dielectric spectrum, we provide evidence from simulations in general support of QF. In particular, as features in the solid's dielectric spectrum begin to overlap with water's librational and Debye modes, we find an increase in friction in line with that proposed by QF. At the microscopic level, we find that this contribution to friction manifests more distinctly in the dynamics of the solid's charge density than that of water. Our findings suggest that experimental signatures of QF may be more pronounced in the solid's response rather than liquid water's.

Characteristics of Health Care Financial Assistance Programs Serving the Most Populous U.S. Counties.

County-based health care financial assistance programs offer improved access to health care for indigent populations by reducing or eliminating costs to receive care. We examined health care financial assistance programs serving the 10 most populous U.S. counties. We found that the percent enrollment in a county's program is strongly correlated with the percent uninsured (r=.86) and the percent undocumented (r=.83), and moderately correlated with the percent indigent (r=.43) in a county, suggesting the importance of health care financial assistance programs for these groups. Furthermore, the typical county-based health care financial assistance program covers the same income range (0-138% federal poverty level) and offers similar benefits (including coverage of emergency care and inpatient care) as Medicaid. Counseling services are frequently available to assist applicants. These characteristics allow them to serve as an alternative source of health care funding to those who are ineligible for Medicaid coverage.

Trade-Off between Redox Potential and the Strength of Electrochemical CO2 Capture in Quinones.

Electrochemical carbon dioxide capture recently emerged as a promising alternative approach to conventional energy-intensive carbon-capture methods. A common electrochemical capture approach is to employ redox-active molecules such as quinones. Upon electrochemical reduction, quinones become activated for the capture of CO2 through a chemical reaction. A key disadvantage of this method is the possibility of side-reactions with oxygen, which is present in almost all gas mixtures of interest for carbon capture. This issue can potentially be mitigated by fine-tuning redox potentials through the introduction of electron-withdrawing groups on the quinone ring. In this article, we investigate the thermodynamics of the electron transfer and chemical steps of CO2 capture in different quinone derivatives with a range of substituents. By combining density functional theory calculations and cyclic voltammetry experiments, we support a previously described trade-off between the redox potential and the strength of CO2 capture. We show that redox potentials can readily be tuned to more positive values to impart stability to oxygen, but significant decreases in CO2 binding free energies are observed as a consequence. Our calculations support this effect for a large series of anthraquinones and benzoquinones. Different trade-off relationships were observed for the two classes of molecules. These trade-offs must be taken into consideration in the design of improved redox-active molecules for electrochemical CO2 capture.

Kallikrein-related peptidase 5 induces miRNA-mediated anti-oncogenic pathways in breast cancer.

Kallikrein-related peptidase 5 (KLK5) displays aberrant expression in cancer. Recently, we showed KLK5 reconstitution in breast cancer cell lines suppresses malignancy. Present study aims to investigate the functional KLK5 mediated miRNA network on breast cancer progression, molecular subtype and survival. 28 miRNAs were up-regulated and 62 miRNAs were down-regulated upon KLK5 expression. Extracellular matrix (ECM) molecules and cell-adhesion pathways were the most significant KLK5-induced miRNA-mediated regulatory targets. Validation from The Cancer Genome Atlas (TCGA) database indicated KLK5 was specifically down-regulated in luminal B and basal-like breast cancer subtypes. There was a correlation between KLK5, miRNAs and their downstream ECM gene targets. Long-term patient survival correlated with dysregulation of KLK5 and interacting ECM target genes. It suggests biological differences between breast cancer molecular subtypes, patient survival, and their propensity for invasion and metastasis can be explained in part by altered miRNA networks induced by KLK5 dysregulation. We provide the first evidence that KLK5 can affect miRNA networks, which regulate MMPs and other novel ECM targets and a new compelling hypothesis of interplay between serine proteases and miRNAs. We developed a combined KLK5-(ITGB1+COL12A1) predictive score for recurrence-free survival that could be exploited in clinical applications.

Multilevel whole-genome analysis reveals candidate biomarkers in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common neoplasm of the kidney. We conducted an integrated analysis of copy number, gene expression (mRNA and miRNA), protein expression, and methylation changes in clear cell renal cell carcinoma (ccRCC). We used a stepwise approach to identify the most significant copy number aberrations (CNA) and identified regions of peak and broad copy number gain and loss, including peak gains (3q21, 5q32, 5q34-q35, 7p11, 7q21, 8q24, 11q13, and 12q14) and deletions (1p36, 2q34-q37, 3p25, 4q33-q35, 6q23-q27, and 9p21). These regions harbor novel tumor-related genes and miRNAs not previously reported in renal carcinoma. Integration of genome-wide expression data and gene set enrichment analysis revealed 75 gene sets significantly altered in tumors with CNAs compared with tumors without aberration. We also identified genes located in peak CNAs with concordant methylation changes (hypomethylated in copy number gains such as STC2 and CCND1 and hypermethylated in deletions such as CLCNKB, VHL, and CDKN2A/2B). For other genes, such as CA9, expression represents the net outcome of opposing forces (deletion and hypomethylation) that also significantly influences patient survival. We also validated the prognostic value of miRNA let-7i in RCCs. miR-138, located in chromosome 3p deletion, was also found to have suppressive effects on tumor proliferation and migration abilities. Our findings provide a significant advance in the delineation of the ccRCC genome by better defining the impact of CNAs in conjunction with methylation changes on the expression of cancer-related genes, miRNAs, and proteins and their influence on patient survival.

Integrated genomic characterization of the kallikrein gene locus in cancer.

BACKGROUND: The kallikrein-related peptidases (KLKs) have been implicated in many types of cancer, including prostate and ovarian. MATERIALS AND METHODS: We performed a comprehensive in silico study to characterize the KLK locus using transcriptomic (gene expression) and genomic (mutations and DNA copy number) data in prostate cancer (n=194), serous ovarian cancer (n=506), glioblastoma multiforme (n=206), and sarcoma (n=207) from The Cancer Genome Atlas and independent publicly available datasets to assess KLKs as cancer biomarkers. RESULTS: Overall, there was mRNA overexpression in prostate and serous ovarian cancer and decreased expression in glioblastoma multiforme. There was higher frequency of genomic loss in serous ovarian cancer, and rare KLK gene mutations observed in serous ovarian cancer and GBM. Dysregulation of KLKs correlates with survival: for prostate cancer, a combination of dysregulation of KLK1, 5 and 13 was associated with worse disease-free survival. CONCLUSION: We conclude that specific dysregulation of KLKs at the genetic and transcriptomic levels have useful prognostic value.

Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs.

Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies and currently no diagnostic marker exists. Kallikrein-related peptidases (KLKs) have been implicated in numerous cancers including ovarian, prostate, and breast carcinoma. KLKs 5, 6, 10, and 11 have decreased expression in RCC when compared to normal kidney tissue. Our bioinformatic analysis indicated that the KLK 1, 6, and 7 genes have decreased expression in RCC. We experimentally verified these results and found that decreased expression of KLKs 1 and 3 were significantly associated with the clear cell RCC subtype (p<0.001). An analysis of miRNAs differentially expressed in RCC showed that 61 of the 117 miRNAs that were reported to be dysregulated in RCC were predicted to target KLKs. We experimentally validated two targets using two independent approaches. Transfection of miR-224 into HEK-293 cells resulted in decreased KLK1 protein levels. A luciferase assay demonstrated that hsa-let-7f can target KLK10 in the RCC cell line ACHN. Our results, showing differential expression of KLKs in RCC, suggest that KLKs could be novel diagnostic markers for RCC and that their dysregulation could be under miRNA control. The observation that KLKs could represent targets for miRNAs suggests a post-transcriptional regulatory mechanism with possible future therapeutic applications.