Trust at Work: A Study on Faith and Trust of Protestant Entrepreneurs in China

There is much talk about the trust crisis in China and the possible role of religion in rebuilding China’s moral order. This study is an attempt to examine religion’s impact on the emerging market economy in China, focusing on trust in business relations that might be generated by the Christian faith. Based on 43 in-depth interviews with Christian entrepreneurs in China, our study shows that the majority of our respondents tend to be: (1) more willing to be trustworthy after becoming Christians; (2) trusting people who share their faith more than others; (3) perceiving religious persons, regardless of what that religion is, as more trustworthy than the non-religious. Our study shows that religiosity is used by many Christian entrepreneurs as a category to guide their decision-making and that it is significant in stimulating and maintaining trust in and from others

Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy.

Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles) involved in AR expression and their possible role as therapeutic targets

lncRNA-dependent mechanisms of androgen-receptor-regulated gene activation programs.

Although recent studies have indicated roles of long non-coding RNAs (lncRNAs) in physiological aspects of cell-type determination and tissue homeostasis, their potential involvement in regulated gene transcription programs remains rather poorly understood. The androgen receptor regulates a large repertoire of genes central to the identity and behaviour of prostate cancer cells, and functions in a ligand-independent fashion in many prostate cancers when they become hormone refractory after initial androgen deprivation therapy. Here we report that two lncRNAs highly overexpressed in aggressive prostate cancer, PRNCR1 (also known as PCAT8) and PCGEM1, bind successively to the androgen receptor and strongly enhance both ligand-dependent and ligand-independent androgen-receptor-mediated gene activation programs and proliferation in prostate cancer cells. Binding of PRNCR1 to the carboxy-terminally acetylated androgen receptor on enhancers and its association with DOT1L appear to be required for recruitment of the second lncRNA, PCGEM1, to the androgen receptor amino terminus that is methylated by DOT1L. Unexpectedly, recognition of specific protein marks by PCGEM1-recruited pygopus 2 PHD domain enhances selective looping of androgen-receptor-bound enhancers to target gene promoters in these cells. In 'resistant' prostate cancer cells, these overexpressed lncRNAs can interact with, and are required for, the robust activation of both truncated and full-length androgen receptor, causing ligand-independent activation of the androgen receptor transcriptional program and cell proliferation. Conditionally expressed short hairpin RNA targeting these lncRNAs in castration-resistant prostate cancer cell lines strongly suppressed tumour xenograft growth in vivo. Together, these results indicate that these overexpressed lncRNAs can potentially serve as a required component of castration-resistance in prostatic tumours

Proteostasis by STUB1/HSP70 complex controls sensitivity to androgen receptor targeted therapy in advanced prostate cancer.

Protein homeostasis (proteostasis) is a potential mechanism that contributes to cancer cell survival and drug resistance. Constitutively active androgen receptor (AR) variants confer anti-androgen resistance in advanced prostate cancer. However, the role of proteostasis involved in next generation anti-androgen resistance and the mechanisms of AR variant regulation are poorly defined. Here we show that the ubiquitin-proteasome-system (UPS) is suppressed in enzalutamide/abiraterone resistant prostate cancer. AR/AR-V7 proteostasis requires the interaction of E3 ubiquitin ligase STUB1 and HSP70 complex. STUB1 disassociates AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 significantly inhibits prostate tumor growth and improves enzalutamide/abiraterone treatments through AR/AR-V7 suppression. Clinically, HSP70 expression is upregulated and correlated with AR/AR-V7 levels in high Gleason score prostate tumors. Our results reveal a novel mechanism of anti-androgen resistance via UPS alteration which could be targeted through inhibition of HSP70 to reduce AR-V7 expression and overcome resistance to AR-targeted therapies

Limiting factors in sub-10 nm scanning-electron-beam lithography

Achieving the highest possible resolution using scanning-electron-beam lithography (SEBL) has become an increasingly urgent problem in recent years, as advances in various nanotechnology applications [ F. S. Bates and G. H. Fredrickson, Annu. Rev. Phys. Chem. 41, 525 (1990) ; Black et al., IBM J. Res. Dev. 51, 605 (2007) ; Yang et al., J. Chem. Phys. 116, 5892 (2002) ] have driven demand for feature sizes well into the sub-10 nm domain, close to the resolution limit of the current generation of SEBL processes. In this work, the authors have used a combination of calculation, modeling, and experiment to investigate the relative effects of resist contrast, beam scattering, secondary electron generation, system spot size, and metrology limitations on SEBL process resolution. In the process of investigating all of these effects, they have also successfully yielded dense structures with a pitch of 12 nm at voltages as low as 10 keV

ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer.

The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa

Ceres' opposition effect observed by the Dawn framing camera

The surface reflectance of planetary regoliths may increase dramatically towards zero phase angle, a phenomenon known as the opposition effect (OE). Two physical processes that are thought to be the dominant contributors to the brightness surge are shadow hiding (SH) and coherent backscatter (CB). The occurrence of shadow hiding in planetary regoliths is self-evident, but it has proved difficult to unambiguously demonstrate CB from remote sensing observations. One prediction of CB theory is the wavelength dependence of the OE angular width. The Dawn spacecraft observed the OE on the surface of dwarf planet Ceres. We characterize the OE over the resolved surface, including the bright Cerealia Facula, and to find evidence for SH and/or CB. We analyze images of the Dawn framing camera by means of photometric modeling of the phase curve. We find that the OE of most of the investigated surface has very similar characteristics, with an enhancement factor of 1.4 and a FWHM of 3{\deg} (broad OE). A notable exception are the fresh ejecta of the Azacca crater, which display a very narrow brightness enhancement that is restricted to phase angles $< 0.5${\deg} (narrow OE); suggestively, this is in the range in which CB is thought to dominate. We do not find a wavelength dependence for the width of the broad OE, and lack the data to investigate the dependence for the narrow OE. The prediction of a wavelength-dependent CB width is rather ambiguous. The zero-phase observations allow us to determine Ceres' visible geometric albedo as $p_V = 0.094 \pm 0.005$. A comparison with other asteroids suggests that Ceres' broad OE is typical for an asteroid of its spectral type, with characteristics that are primarily linked to surface albedo. Our analysis suggests that CB may occur on the dark surface of Ceres in a highly localized fashion.Comment: Credit: Schr\"oder et al, A&A in press, 2018, reproduced with permission, \copyright ES

Natural Bacterial Communities Serve as Quantitative Geochemical Biosensors

Biological sensors can be engineered to measure a wide range of environmental conditions. Here we show that statistical analysis of DNA from natural microbial communities can be used to accurately identify environmental contaminants, including uranium and nitrate at a nuclear waste site. In addition to contamination, sequence data from the 16S rRNA gene alone can quantitatively predict a rich catalogue of 26 geochemical features collected from 93 wells with highly differing geochemistry characteristics. We extend this approach to identify sites contaminated with hydrocarbons from the Deepwater Horizon oil spill, finding that altered bacterial communities encode a memory of prior contamination, even after the contaminants themselves have been fully degraded. We show that the bacterial strains that are most useful for detecting oil and uranium are known to interact with these substrates, indicating that this statistical approach uncovers ecologically meaningful interactions consistent with previous experimental observations. Future efforts should focus on evaluating the geographical generalizability of these associations. Taken as a whole, these results indicate that ubiquitous, natural bacterial communities can be used as in situ environmental sensors that respond to and capture perturbations caused by human impacts. These in situ biosensors rely on environmental selection rather than directed engineering, and so this approach could be rapidly deployed and scaled as sequencing technology continues to become faster, simpler, and less expensive