Ultrasensitive force and displacement detection using trapped ions

The ability to detect extremely small forces is vital for a variety of disciplines including precision spin-resonance imaging, microscopy, and tests of fundamental physical phenomena. Current force-detection sensitivity limits have surpassed 1 $aN/\sqrt{Hz}$ (atto $=10^{-18}$) through coupling of micro or nanofabricated mechanical resonators to a variety of physical systems including single-electron transistors, superconducting microwave cavities, and individual spins. These experiments have allowed for probing studies of a variety of phenomena, but sensitivity requirements are ever-increasing as new regimes of physical interactions are considered. Here we show that trapped atomic ions are exquisitely sensitive force detectors, with a measured sensitivity more than three orders of magnitude better than existing reports. We demonstrate detection of forces as small as 174 $yN$ (yocto $=10^{-24}$), with a sensitivity 390$\pm150$ $yN/\sqrt{Hz}$ using crystals of $n=60$ $^{9}$Be$^{+}$ ions in a Penning trap. Our technique is based on the excitation of normal motional modes in an ion trap by externally applied electric fields, detection via and phase-coherent Doppler velocimetry, which allows for the discrimination of ion motion with amplitudes on the scale of nanometers. These experimental results and extracted force-detection sensitivities in the single-ion limit validate proposals suggesting that trapped atomic ions are capable of detecting of forces with sensitivity approaching 1 $yN/\sqrt{Hz}$. We anticipate that this demonstration will be strongly motivational for the development of a new class of deployable trapped-ion-based sensors, and will permit scientists to access new regimes in materials science.Comment: Expanded introduction and analysis. Methods section added. Subject to press embarg

Combating subclonal evolution of resistant cancer phenotypes

Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these phenotypes pre-exist in pre-treatment subclones that become dominant after chemotherapy, indicating selection for resistance phenotypes. Post-chemotherapy cancer cells are effectively treated with drugs targeting acquired phenotypes. These findings highlight cancer's ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves

Feed Mitigant Efficacy for Control of Porcine Epidemic Diarrhea Virus and Porcine Reproductive and Respiratory Syndrome Virus when Inoculated Alone or Together in Feed

Research has demonstrated that swine feed can be a fomite for viral transmission and feed additives can reduce viral contamination. Therefore, the objective of this study was to evaluate two feed additives in feed contaminated with PEDV or PRRSV. Feed additives included: no treatment, 0.33% commercial formaldehyde-based product, and 0.50% medium chain fatty acids (MCFA) blend. Feed samples were inoculated with PEDV and PRRSV alone or together at an inoculation concentration of 106 TCID50/g for each virus. Once inoculated, feed was stored at room temperature for 24 h before analyzing via qRT-PCR. For samples inoculated with PEDV or PRRSV alone, a quantitative real time reverse transcription PCR (qRT-PCR) assay was used, which was designed to detect PEDV or PRRSV nucleic acid. For co-inoculated samples, an assay was designed to detect PEDV and PRRSV within a single assay. For PEDV alone, there was marginally significant evidence that feed additives resulted in differences in cycle threshold (Ct) value (P = 0.052), but no evidence was observed for pairwise differences. For PRRSV alone, formaldehyde increased Ct compared to the untreated control and MCFA treatment (P \u3c 0.05). For co-infection of PRRSV and PEDV, MCFA and formaldehyde increased Ct (P \u3c 0.05) in comparison to non-treated feed. In summary, formaldehyde increased Ct values in feed when contaminated with PRRSV while both feed additives increased Ct in feed when co-inoculated with PRRSV and PEDV. This study also provided evidence that the co-inoculation model can effectively evaluate mitigants

Feed Mitigant Efficacy for Control of Porcine Epidemic Diarrhea Virus and Porcine Reproductive and Respiratory Syndrome Virus when Inoculated Alone or Together in Feed

Research has demonstrated that swine feed can be a fomite for viral transmission and feed additives can reduce viral contamination. Therefore, the objective of this study was to evaluate two feed additives in feed contaminated with PEDV or PRRSV. Feed additives included: no treatment, 0.33% commercial formaldehyde-based product, and 0.50% medium chain fatty acids (MCFA) blend. Feed samples were inoculated with PEDV and PRRSV alone or together at an inoculation concentration of 106 TCID50/g for each virus. Once inoculated, feed was stored at room temperature for 24 h before analyzing via qRT-PCR. For samples inoculated with PEDV or PRRSV alone, a quantitative real time reverse transcription PCR (qRT-PCR) assay was used, which was designed to detect PEDV or PRRSV nucleic acid. For co-inoculated samples, an assay was designed to detect PEDV and PRRSV within a single assay. For PEDV alone, there was marginally significant evidence that feed additives resulted in differences in cycle threshold (Ct) value (P = 0.052), but no evidence was observed for pairwise differences. For PRRSV alone, formaldehyde increased Ct compared to the untreated control and MCFA treatment (P \u3c 0.05). For co-infection of PRRSV and PEDV, MCFA and formaldehyde increased Ct (P \u3c 0.05) in comparison to non-treated feed. In summary, formaldehyde increased Ct values in feed when contaminated with PRRSV while both feed additives increased Ct in feed when co-inoculated with PRRSV and PEDV. This study also provided evidence that the co-inoculation model can effectively evaluate mitigants

Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

SummarySomatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts