The potential for liquid biopsies in the precision medical treatment of breast cancer.

Currently the clinical management of breast cancer relies on relatively few prognostic/predictive clinical markers (estrogen receptor, progesterone receptor, HER2), based on primary tumor biology. Circulating biomarkers, such as circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) may enhance our treatment options by focusing on the very cells that are the direct precursors of distant metastatic disease, and probably inherently different than the primary tumor's biology. To shift the current clinical paradigm, assessing tumor biology in real time by molecularly profiling CTCs or ctDNA may serve to discover therapeutic targets, detect minimal residual disease and predict response to treatment. This review serves to elucidate the detection, characterization, and clinical application of CTCs and ctDNA with the goal of precision treatment of breast cancer

Unusually Weak Diffuse Interstellar Bands toward HD 62542

As part of an extensive survey of diffuse interstellar bands (DIBs), we have obtained optical spectra of the moderately reddened B5V star HD 62542, which is known to have an unusual UV extinction curve of the type usually identified with dark clouds. The typically strongest of the commonly catalogued DIBs covered by the spectra -- those at 5780, 5797, 6270, 6284, and 6614 A -- are essentially absent in this line of sight, in marked contrast with other lines of sight of similar reddening. We compare the HD 62542 line of sight with others exhibiting a range of extinction properties and molecular abundances and interpret the weakness of the DIBs as an extreme case of deficient DIB formation in a dense cloud whose more diffuse outer layers have been stripped away. We comment on the challenges these observations pose for identifying the carriers of the diffuse bands.Comment: 20 pages, 4 figures; aastex; accepted by Ap

A unified dataset of colocated sewage pollution, periphyton, and benthic macroinvertebrate community and food web structure from Lake Baikal (Siberia)

Sewage released from lakeside development can introduce nutrients and micropollutants that can restructure aquatic ecosystems. Lake Baikal, the world’s most ancient, biodiverse, and voluminous freshwater lake, has been experiencing localized sewage pollution from lakeside settlements. Nearby increasing filamentous algal abundance suggests benthic communities are responding to localized pollution. We surveyed 40-km of Lake Baikal’s southwestern shoreline from 19 to 23 August 2015 for sewage indicators, including pharmaceuticals, personal care products, and microplastics, with colocated periphyton, macroinvertebrate, stable isotope, and fatty acid samplings. The data are structured in a tidy format (a tabular arrangement familiar to limnologists) to encourage reuse. Unique identifiers corresponding to sampling locations are retained throughout all data files to facilitate interoperability among the dataset’s 150+ variables. For Lake Baikal studies, these data can support continued monitoring and research efforts. For global studies of lakes, these data can help characterize sewage prevalence and ecological consequences of anthropogenic disturbance across spatial scales

Circulating Tumor Cell Transcriptomics as Biopsy Surrogates in Metastatic Breast Cancer

BACKGROUND Metastatic breast cancer (MBC) and the circulating tumor cells (CTCs) leading to macrometastases are inherently different than primary breast cancer. We evaluated whether whole transcriptome RNA-Seq of CTCs isolated via an epitope-independent approach may serve as a surrogate for biopsies of macrometastases. METHODS We performed RNA-Seq on fresh metastatic tumor biopsies, CTCs, and peripheral blood (PB) from 19 newly diagnosed MBC patients. CTCs were harvested using the ANGLE Parsortix microfluidics system to isolate cells based on size and deformability, independent of a priori knowledge of cell surface marker expression. RESULTS Gene expression separated CTCs, metastatic biopsies, and PB into distinct groups despite heterogeneity between patients and sample types. CTCs showed higher expression of immune oncology targets compared with corresponding metastases and PB. Predictive biomarker (n = 64) expression was highly concordant for CTCs and metastases. Repeat observation data post-treatment demonstrated changes in the activation of different biological pathways. Somatic single nucleotide variant analysis showed increasing mutational complexity over time. CONCLUSION We demonstrate that RNA-Seq of CTCs could serve as a surrogate biomarker for breast cancer macrometastasis and yield clinically relevant insights into disease biology and clinically actionable targets

Effects of spatially heterogeneous lakeside development on nearshore biotic communities in a large, deep, oligotrophic lake

Sewage released from lakeside development can reshape ecological communities. Nearshore periphyton can rapidly assimilate sewage-associated nutrients, leading to increases of filamentous algal abundance, thus altering both food abundance and quality for grazers. In Lake Baikal, a large, ultra-oligotrophic, remote lake in Siberia, filamentous algal abundance has increased near lakeside developments, and localized sewage input is the suspected cause. These shifts are of particular interest in Lake Baikal, where endemic littoral biodiversity is high, lakeside settlements are mostly small, tourism is relatively high (~1.2 million visitors annually), and settlements are separated by large tracts of undisturbed shoreline, enabling investigation of heterogeneity and gradients of disturbance. We surveyed sites along 40 km of Baikal’s southwestern shore for sewage indicators—pharmaceuticals and personal care products (PPCPs) and microplastics—as well as periphyton and macroinvertebrate abundance and indicators of food web structure (stable isotopes and fatty acids). Summed PPCP concentrations were spatially related to lakeside development. As predicted, lakeside development was associated with more filamentous algae and lower abundance of sewagesensitive mollusks. Periphyton and macroinvertebrate stable isotopes and essential fatty acids suggested that food web structure otherwise remained similar across sites; yet, the invariance of amphipod fatty acid composition, relative to periphyton, suggested that grazers adjust behavior or metabolism to compensate for different periphyton assemblages. Our results demonstrate that even low levels of human disturbance can result in spatial heterogeneity of nearshore ecological responses, with potential for changing trophic interactions that propagate through the food web

Formaldehyde over North America and the North Atlantic during the summer 2004 INTEX campaign: Methods, observed distributions, and measurement‐model comparisons

A tunable diode laser absorption spectrometer (TDLAS) was operated on the NASA DC‐8 aircraft during the summer INTEX‐NA study to acquire ambient formaldehyde (CH2O) measurements over North America and the North Atlantic Ocean from ∼0.2 km to ∼12.5 km altitude spanning 17 science flights. Measurements of CH2O in the boundary layer and upper troposphere over the southeastern United States were anomalously low compared to studies in other years, and this was attributed to the record low temperatures over this region during the summer of 2004. Formaldehyde is primarily formed over the southeast from isoprene, and isoprene emissions are strongly temperature‐dependent. Despite this effect, the median upper tropospheric (UT) CH2O mixing ratio of 159 pptv from the TDLAS over continental North America is about a factor of 4 times higher than the median UT value of 40 pptv observed over remote regions during TRACE‐P. These observations together with the higher variability observed in this study all point to the fact that continental CH2O levels in the upper troposphere were significantly perturbed during the summer of 2004 relative to more typical background levels in the upper troposphere over more remote regions. The TDLAS measurements discussed in this paper are employed together with box model results in the companion paper by Fried et al. to further examine enhanced CH2O distributions in the upper troposphere due to convection. Measurements of CH2O on the DC‐8 were also acquired by a coil enzyme fluorometric system and compared with measurements from the TDLAS system

Intrinsic electrochemical activity of single walled carbon nanotube–Nafion assemblies

The intrinsic electrochemical properties and activity of single walled carbon nanotube (SWNT) network electrodes modified by a drop-cast Nafion film have been determined using the one electron oxidation of ferrocene trimethyl ammonium (FcTMA+) as a model redox probe in the Nafion film. Facilitated by the very low transport coefficient of FcTMA+ in Nafion (apparent diffusion coefficient of 1.8 × 10−10 cm2 s−1), SWNTs in the 2-D network behave as individual elements, at short (practical) times, each with their own characteristic diffusion, independent of neighbouring sites, and the response is diagnostic of the proportion of SWNTs active in the composite. Data are analysed using candidate models for cases where: (i) electron transfer events only occur at discrete sites along the sidewall (with a defect density typical of chemical vapour deposition SWNTs); (ii) all of the SWNTs in a network are active. The first case predicts currents that are much smaller than seen experimentally, indicating that significant portions of SWNTs are active in the SWNT–Nafion composite. However, the predictions for a fully active SWNT result in higher currents than seen experimentally, indicating that a fraction of SWNTs are not connected and/or that not all SWNTs are wetted completely by the Nafion film to provide full access of the redox mediator to the SWNT surface