We propose a new method for determining the target genes of transcriptional enhancers in specific cells and tissues. It combines global trends across many samples and sample-specific information, and ...considers the joint effect of multiple enhancers. Our method outperforms existing methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent experimental data. Requiring few types of input data, we are able to apply our method to reconstruct the enhancer-target networks in 935 samples of human primary cells, tissues and cell lines, which constitute by far the largest set of enhancer-target networks. The similarity of these networks from different samples closely follows their cell and tissue lineages. We discover three major co-regulation modes of enhancers and find defense-related genes often simultaneously regulated by multiple enhancers bound by different transcription factors. We also identify differentially methylated enhancers in hepatocellular carcinoma (HCC) and experimentally confirm their altered regulation of HCC-related genes.
Summary
This meta‐analysis investigates the direction and strength of the relationship between diversity in culturally diverse teams and team creativity/innovation. We distinguish the effects of two ...diversity levels (i.e., surface level vs. deep level) in culturally diverse teams and examine the moderators suggested by the socio‐technical systems framework (i.e., team virtuality and task characteristics in terms of task interdependence, complexity, and intellectiveness). Surface‐level diversity in culturally diverse teams is not related to team creativity/innovation, whereas deep‐level diversity in culturally diverse teams is positively related to team creativity/innovation. Moreover, surface‐level diversity in culturally diverse teams and team creativity/innovation are negatively related for simple tasks but unrelated for complex tasks. Deep‐level diversity in culturally diverse teams and team creativity/innovation is positively related for collocated teams and interdependent tasks but unrelated for noncollocated teams and independent tasks. We discuss the theoretical and practical implications.
Prostate cancer is the most common cancer and second leading cause of cancer-related death in American men. Antiandrogen therapies are part of the standard of therapeutic regimen for advanced or ...metastatic prostate cancers; however, patients who receive these treatments are more likely to develop castration-resistant prostate cancer (CRPC) or neuroendocrine prostate cancer (NEPC). In the development of CRPC or NEPC, numerous genetic signaling pathways have been under preclinical investigations and in clinical trials. Accumulated evidence shows that DNA methylation, chromatin integrity, and accessibility for transcriptional regulation still play key roles in prostate cancer initiation and progression. Better understanding of how epigenetic change regulates the progression of prostate cancer and the interaction between epigenetic and genetic modulators driving NEPC may help develop a better risk stratification and more effective treatment regimens for prostate cancer patients.
•Patients who receive antiandrogen treatments are more likely to develop CRPC.•A genomic landscape study has identified aberrant epigenetic events in CRPC and NEPC development.•Epigenetic targeting may represent an alternative therapeutic regimen for advanced prostate cancer.•Ongoing preclinical and clinical trials have shed light on the advantage of combination therapies.
Charge transport across metal-molecule interfaces has an important role in organic electronics. Typically, chemical link groups such as thiols or amines are used to bind organic molecules to metal ...electrodes in single-molecule circuits, with these groups controlling both the physical structure and the electronic coupling at the interface. Direct metal-carbon coupling has been shown through C60, benzene and π-stacked benzene, but ideally the carbon backbone of the molecule should be covalently bonded to the electrode without intervening link groups. Here, we demonstrate a method to create junctions with such contacts. Trimethyl tin (SnMe(3))-terminated polymethylene chains are used to form single-molecule junctions with a break-junction technique. Gold atoms at the electrode displace the SnMe(3) linkers, leading to the formation of direct Au-C bonded single-molecule junctions with a conductance that is ∼100 times larger than analogous alkanes with most other terminations. The conductance of these Au-C bonded alkanes decreases exponentially with molecular length, with a decay constant of 0.97 per methylene, consistent with a non-resonant transport mechanism. Control experiments and ab initio calculations show that high conductances are achieved because a covalent Au-C sigma (σ) bond is formed. This offers a new method for making reproducible and highly conducting metal-organic contacts.
We perform a perturbative calculation of the third order optical conductivities of doped graphene, using approximations valid around the Dirac points and neglecting effects due to scattering and ...electron-electron interactions. In this limit analytic formulas can be constructed for the conductivities. We discuss in detail the results for third harmonic generation, the Kerr effect and two-photon carrier injection, parametric frequency conversion, and two-color coherent current injection. We find a complicated dependence on the chemical potential and photon energies. The linear dispersion causes resonances over a wide range of photon energies, and it is possible to obtain large optical nonlinearities by tuning the chemical potential.
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