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Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in vitro functional assays, we here demonstrate that NgR2 is crucial in promoting cell adhesion to αVβ3 ligands. Moreover, we describe for the first time co-fractionation of αVβ3 integrin and NgR2 in small extracellular vesicles derived from metastatic prostate cancer patients plasma. These prostate cancer patient-derived small extracellular vesicles have a functional impact on human monocytes, increasing their adhesion to fibronectin. The monocytes incubated with small extracellular vesicles do not show an associated change in conventional polarization marker expression and appear to be in an early stage that may be defined as adhesion competent. Overall, these findings allow us to better understand integrin-directed signaling and cell-cell communication during cancer progression. Furthermore, our results pave the way for new diagnostic and therapeutic perspectives for patients affected by neuroendocrine prostate cancer.

Boron neutron capture therapy (BNCT) is a cellular-level hadron therapy achieving therapeutic effects via the synergistic action of multiple particles, including Lithium, alpha, proton, and photon. However, evaluating the relative biological effectiveness (RBE) in BNCT remains challenging. In this research, we performed a microdosimetric calculation for BNCT using the Monte Carlo track structure (MCTS) simulation toolkit, TOPAS-nBio. This paper reports the first attempt to derive the ionization cross-sections of low-energy (>0.025 MeV/u) Lithium for MCTS simulation based on the effective charge cross-section scalation method and phenomenological double-parameter modification. The fitting parameters λ1=1.101,λ2=3.486 were determined to reproduce the range and stopping power data from the ICRU report 73. Besides, the lineal energy spectra of charged particles in BNCT were calculated, and the influence of sensitive volume (SV) size was discussed. Condensed history simulation obtained similar results with MCTS when using Micron-SV while overestimating the lineal energy when using Nano-SV. Furthermore, we found that the microscopic boron distribution can significantly affect the lineal energy for Lithium, while the effect for alpha is minimal. Similar results to the published data by PHITS simulation were observed for the compound particles and monoenergetic protons when using micron-SV. Spectra with nano-SV reflected that the different track densities and absorbed doses in the nucleus together result in the dramatic difference in the macroscopic biological response of BPA and BSH. This work and the developed methodology could impact the research fields in BNCT where understanding radiation effects is crucial, such as the treatment planning system, source evaluation, and new boron drug development.

The organic carbon (Corg) stored in seagrass meadows is globally significant and could be relevant in strategies to mitigate increasing CO2 concentration in the atmosphere. Most of that stored Corg is in the soils that underlie the seagrasses. We explored how seagrass and soil characteristics vary among seagrass meadows across the geographic range of turtlegrass (Thalassia testudinum) with a goal of illuminating the processes controlling soil organic carbon (Corg) storage spanning 23° of latitude. Seagrass abundance (percent cover, biomass, and canopy height) varied by over an order of magnitude across sites, and we found high variability in soil characteristics, with Corg ranging from 0.08 to 12.59% dry weight. Seagrass abundance was a good predictor of the Corg stocks in surficial soils, and the relative importance of seagrass-derived soil Corg increased as abundance increased. These relationships suggest that first-order estimates of surficial soil Corg stocks can be made by measuring seagrass abundance and applying a linear transfer function. The relative availability of the nutrients N and P to support plant growth was also correlated with soil Corg stocks. Stocks were lower at N-limited sites than at P-limited ones, but the importance of seagrass-derived organic matter to soil Corg stocks was not a function of nutrient limitation status. This finding seemed at odds with our observation that labile standard substrates decomposed more slowly at N-limited than at P-limited sites, since even though decomposition rates were 55% lower at N-limited sites, less Corg was accumulating in the soils. The dependence of Corg stocks and decomposition rates on nutrient availability suggests that eutrophication is likely to exert a strong influence on carbon storage in seagrass meadows.

Environmental degradation has the potential to alter key mutualisms that underlie the structure and function of ecological communities. How microbial communities associated with fishes vary across populations and in relation to habitat characteristics remains largely unknown despite their fundamental roles in host nutrition and immunity. We find significant differences in the gut microbiome composition of a facultative coral-feeding butterflyfish (Chaetodon capistratus) across Caribbean reefs that differ markedly in live coral cover (∼0-30%). Fish gut microbiomes were significantly more variable at degraded reefs, a pattern driven by changes in the relative abundance of the most common taxa potentially associated with stress. We also demonstrate that fish gut microbiomes on severely degraded reefs have a lower abundance of Endozoicomonas and a higher diversity of anaerobic fermentative bacteria, which may suggest a less coral dominated diet. The observed shifts in fish gut bacterial communities across the habitat gradient extend to a small set of potentially beneficial host associated bacteria (i.e., the core microbiome) suggesting essential fish-microbiome interactions may be vulnerable to severe coral degradation.

ObjectiveWe develop natural language processing (NLP) methods capable of accurately classifying tumor attributes from pathology reports given minimal labeled examples. Our hierarchical cancer to cancer transfer (HCTC) and zero-shot string similarity (ZSS) methods are designed to exploit shared information between cancers and auxiliary class features, respectively, to boost performance using enriched annotations which give both location-based information and document level labels for each pathology report.Materials and methodsOur data consists of 250 pathology reports each for kidney, colon, and lung cancer from 2002 to 2019 from a single institution (UCSF). For each report, we classified 5 attributes: procedure, tumor location, histology, grade, and presence of lymphovascular invasion. We develop novel NLP techniques involving transfer learning and string similarity trained on enriched annotations. We compare HCTC and ZSS methods to the state-of-the-art including conventional machine learning methods as well as deep learning methods.ResultsFor our HCTC method, we see an improvement of up to 0.1 micro-F1 score and 0.04 macro-F1 averaged across cancer and applicable attributes. For our ZSS method, we see an improvement of up to 0.26 micro-F1 and 0.23 macro-F1 averaged across cancer and applicable attributes. These comparisons are made after adjusting training data sizes to correct for the 20% increase in annotation time for enriched annotations compared to ordinary annotations.ConclusionsMethods based on transfer learning across cancers and augmenting information methods with string similarity priors can significantly reduce the amount of labeled data needed for accurate information extraction from pathology reports.

ObjectiveWe develop natural language processing (NLP) methods capable of accurately classifying tumor attributes from pathology reports given minimal labeled examples. Our hierarchical cancer to cancer transfer (HCTC) and zero-shot string similarity (ZSS) methods are designed to exploit shared information between cancers and auxiliary class features, respectively, to boost performance using enriched annotations which give both location-based information and document level labels for each pathology report.Materials and methodsOur data consists of 250 pathology reports each for kidney, colon, and lung cancer from 2002 to 2019 from a single institution (UCSF). For each report, we classified 5 attributes: procedure, tumor location, histology, grade, and presence of lymphovascular invasion. We develop novel NLP techniques involving transfer learning and string similarity trained on enriched annotations. We compare HCTC and ZSS methods to the state-of-the-art including conventional machine learning methods as well as deep learning methods.ResultsFor our HCTC method, we see an improvement of up to 0.1 micro-F1 score and 0.04 macro-F1 averaged across cancer and applicable attributes. For our ZSS method, we see an improvement of up to 0.26 micro-F1 and 0.23 macro-F1 averaged across cancer and applicable attributes. These comparisons are made after adjusting training data sizes to correct for the 20% increase in annotation time for enriched annotations compared to ordinary annotations.ConclusionsMethods based on transfer learning across cancers and augmenting information methods with string similarity priors can significantly reduce the amount of labeled data needed for accurate information extraction from pathology reports.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Metabolic labeling is a widely used tool to investigate different aspects of pre-mRNA splicing and RNA turnover. The labeling technology takes advantage of native cellular machineries where a nucleotide analog is readily taken up and incorporated into nascent RNA. One such analog is 4-thiouridine (4sU). Previous studies demonstrated that the uptake of 4sU at elevated concentrations (>50μM) and extended exposure led to inhibition of rRNA synthesis and processing, presumably induced by changes in RNA secondary structure. Thus, it is possible that 4sU incorporation may also interfere with splicing efficiency. To test this hypothesis, we carried out splicing analyses of pre-mRNA substrates with varying levels of 4sU incorporation (0-100%). We demonstrate that increased incorporation of 4sU into pre-mRNAs decreased splicing efficiency. The overall impact of 4sU labeling on pre-mRNA splicing efficiency negatively correlates with the strength of splice site signals such as the 3' and the 5' splice sites. Introns with weaker splice sites are more affected by the presence of 4sU. We also show that transcription by T7 polymerase and pre-mRNA degradation kinetics were impacted at the highest levels of 4sU incorporation. Increased incorporation of 4sU caused elevated levels of abortive transcripts, and fully labeled pre-mRNA is more stable than its uridine-only counterpart. Cell culture experiments show that a small number of alternative splicing events were modestly, but statistically significantly influenced by metabolic labeling with 4sU at concentrations considered to be tolerable (40 μM). We conclude that at high 4sU incorporation rates small, but noticeable changes in pre-mRNA splicing can be detected when splice sites deviate from consensus. Given these potential 4sU artifacts, we suggest that appropriate controls for metabolic labeling experiments need to be included in future labeling experiments.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

The global distribution of primary production and consumption by humans (fisheries) is well-documented, but we have no map linking the central ecological process of consumption within food webs to temperature and other ecological drivers. Using standardized assays that span 105° of latitude on four continents, we show that rates of bait consumption by generalist predators in shallow marine ecosystems are tightly linked to both temperature and the composition of consumer assemblages. Unexpectedly, rates of consumption peaked at midlatitudes (25 to 35°) in both Northern and Southern Hemispheres across both seagrass and unvegetated sediment habitats. This pattern contrasts with terrestrial systems, where biotic interactions reportedly weaken away from the equator, but it parallels an emerging pattern of a subtropical peak in marine biodiversity. The higher consumption at midlatitudes was closely related to the type of consumers present, which explained rates of consumption better than consumer density, biomass, species diversity, or habitat. Indeed, the apparent effect of temperature on consumption was mostly driven by temperature-associated turnover in consumer community composition. Our findings reinforce the key influence of climate warming on altered species composition and highlight its implications for the functioning of Earth's ecosystems.

ObjectiveCancer is a leading cause of death, but much of the diagnostic information is stored as unstructured data in pathology reports. We aim to improve uncertainty estimates of machine learning-based pathology parsers and evaluate performance in low data settings.Materials and methodsOur data comes from the Urologic Outcomes Database at UCSF which includes 3232 annotated prostate cancer pathology reports from 2001 to 2018. We approach 17 separate information extraction tasks, involving a wide range of pathologic features. To handle the diverse range of fields, we required 2 statistical models, a document classification method for pathologic features with a small set of possible values and a token extraction method for pathologic features with a large set of values. For each model, we used isotonic calibration to improve the model's estimates of its likelihood of being correct.ResultsOur best document classifier method, a convolutional neural network, achieves a weighted F1 score of 0.97 averaged over 12 fields and our best extraction method achieves an accuracy of 0.93 averaged over 5 fields. The performance saturates as a function of dataset size with as few as 128 data points. Furthermore, while our document classifier methods have reliable uncertainty estimates, our extraction-based methods do not, but after isotonic calibration, expected calibration error drops to below 0.03 for all extraction fields.ConclusionsWe find that when applying machine learning to pathology parsing, large datasets may not always be needed, and that calibration methods can improve the reliability of uncertainty estimates.

ObjectiveCancer is a leading cause of death, but much of the diagnostic information is stored as unstructured data in pathology reports. We aim to improve uncertainty estimates of machine learning-based pathology parsers and evaluate performance in low data settings.Materials and methodsOur data comes from the Urologic Outcomes Database at UCSF which includes 3232 annotated prostate cancer pathology reports from 2001 to 2018. We approach 17 separate information extraction tasks, involving a wide range of pathologic features. To handle the diverse range of fields, we required 2 statistical models, a document classification method for pathologic features with a small set of possible values and a token extraction method for pathologic features with a large set of values. For each model, we used isotonic calibration to improve the model's estimates of its likelihood of being correct.ResultsOur best document classifier method, a convolutional neural network, achieves a weighted F1 score of 0.97 averaged over 12 fields and our best extraction method achieves an accuracy of 0.93 averaged over 5 fields. The performance saturates as a function of dataset size with as few as 128 data points. Furthermore, while our document classifier methods have reliable uncertainty estimates, our extraction-based methods do not, but after isotonic calibration, expected calibration error drops to below 0.03 for all extraction fields.ConclusionsWe find that when applying machine learning to pathology parsing, large datasets may not always be needed, and that calibration methods can improve the reliability of uncertainty estimates.

Systems neuroscience research is increasingly possible through the use of integrated molecular and circuit-level analyses. These studies depend on the use of animal models and, in many cases, molecular and circuit-level analyses. Associated with genetic, pharmacologic, epigenetic, and other types of environmental manipulations. We illustrate typical pitfalls resulting from poor validation of behavior tests. We describe experimental designs and enumerate controls needed to improve reproducibility in investigating and reporting of behavioral phenotypes.

Introduction Demand for dermatologic services in safety net hospitals, which disproportionately serve patients with darker coloured skin, is growing. Teledermatology has the potential to increase access and improve outcomes, but studies have yet to demonstrate the reliability of teledermatology for all Fitzpatrick skin types. Methods We assessed the reliability of teledermatologists' diagnoses and management recommendations for store-and-forward teledermatology in patients with lightly pigmented (Fitzpatrick skin types I-III) versus darkly pigmented (Fitzpatrick skin types IV-VI) skin, when compared to in-person diagnosis and management decisions. This prospective study enrolled 232 adult patients, presenting with new, visible skin complaints in a Los Angeles county dermatology clinic. Forty-seven percent of patients were Fitzpatrick skin types I-III, and 53% were Fitzpatrick skin types IV-VI. Results Percent concordance for the identical primary diagnosis was 53.2% in lighter (Fitzpatrick I-III) skin types and 56.0% in darker (Fitzpatrick IV-VI) skin types. There was no statistically significant difference in concordance rates between lighter and darker skin types for primary diagnosis. Concordance rates for diagnostic testing, clinic-based therapy, and treatments were similar in both groups of Fitzpatrick skin types. Discussion These results suggest that teledermatology is reliable for the diagnosis and management of patients with all Fitzpatrick skin types.

In this study pollinators visiting highbush blueberry fields set in landscapes with differing land use pattern in south-central Chile were investigated. Effects of spatial buffers from 0.5 to 8 km around each blueberry field on the abundance of the main wild pollinator, Bombus terrestris queens, were tested. Wild B. terrestris abundances were positively affected by natural forest area and negatively affected by high-food resource area, and these effects were strongest at a buffer radius of 1 and 3.5 km, respectively. Possibly, continuous food resources provided by natural forest areas favor colony establishment and growth, and/or increase overwintering survival of bumblebee queens. Also, pollinator dependent crop area can generate a “transient dilution effect” by decreasing the density of bumblebees in simultaneously flowering crops. Management strategies might increase crop pollination services by considering the importance of nesting and overwintering habitat quality/amount and area of simultaneously flowering crops requiring insect pollination.

In this study pollinators visiting highbush blueberry fields set in landscapes with differing land use pattern in south-central Chile were investigated. Effects of spatial buffers from 0.5 to 8 km around each blueberry field on the abundance of the main wild pollinator, Bombus terrestris queens, were tested. Wild B. terrestris abundances were positively affected by natural forest area and negatively affected by high-food resource area, and these effects were strongest at a buffer radius of 1 and 3.5 km, respectively. Possibly, continuous food resources provided by natural forest areas favor colony establishment and growth, and/or increase overwintering survival of bumblebee queens. Also, pollinator dependent crop area can generate a “transient dilution effect” by decreasing the density of bumblebees in simultaneously flowering crops. Management strategies might increase crop pollination services by considering the importance of nesting and overwintering habitat quality/amount and area of simultaneously flowering crops requiring insect pollination.

Using data from four deep fields (COSMOS, AEGIS, ECDFS, and CDFN), we studythe correlation between the position of galaxies in the star formation rate(SFR) versus stellar mass plane and local environment at $z10^{10.4-10.6}$ $M_{\odot}$), across all environments. At high redshift ($0.5

We have used the Planck all-sky submillimetre and millimetre maps to search for rare sources distinguished by extreme brightness, a few hundred millijanskies, and their potential for being situated at high redshift. These "cold" Planck sources, selected using the High Frequency Instrument (HFI) directly from the maps and from the Planck Catalogue of Compact Sources (PCCS), all satisfy the criterion of having their rest-frame far-infrared peak redshifted to the frequency range 353-857 GHz. This colour-selection favours galaxies in the redshift range z = 2-4, which we consider as cold peaks in the cosmic infrared background. With a 4.′5 beam at the four highest frequencies, our sample is expected to include overdensities of galaxies in groups or clusters, lensed galaxies, and chance line-of-sight projections. We perform a dedicated Herschel-SPIRE follow-up of 234 such Planck targets, finding a significant excess of red 350 and 500 μm sources, in comparison to reference SPIRE fields. About 94% of the SPIRE sources in the Planck fields are consistent with being overdensities of galaxies peaking at 350 μm, with 3% peaking at 500 μm, and none peaking at 250 μm. About 3% are candidate lensed systems, all 12 of which have secure spectroscopic confirmations, placing them at redshifts z > 2.2. Only four targets are Galactic cirrus, yielding a success rate in our search strategy for identifying extragalactic sources within the Planck beam of better than 98%. The galaxy overdensities are detected with high significance, half of the sample showing statistical significance above 10σ. The SPIRE photometric redshifts of galaxies in overdensities suggest a peak at z ≃ 2, assuming a single common dust temperature for the sources of Td = 35 K. Under this assumption, we derive an infrared (IR) luminosity for each SPIRE source of about 4 × 1012 L⊙, yielding star formation rates of typically 700 M⊙ yr-1. If the observed overdensities are actual gravitationally-bound structures, the total IR luminosity of all their SPIRE-detected sources peaks at 4 × 1013 L⊙, leading to total star formation rates of perhaps 7 × 103 M⊙yr-1 per overdensity. Taken together, these sources show the signatures of high-z (z > 2) protoclusters of intensively star-forming galaxies. All these observations confirm the uniqueness of our sample compared to reference samples and demonstrate the ability of the all-sky Planck-HFI cold sources to select populations of cosmological and astrophysical interest for structure formation studies.

We have used the Planck all-sky submillimetre and millimetre maps to search for rare sources distinguished by extreme brightness, a few hundred millijanskies, and their potential for being situated at high redshift. These "cold" Planck sources, selected using the High Frequency Instrument (HFI) directly from the maps and from the Planck Catalogue of Compact Sources (PCCS), all satisfy the criterion of having their rest-frame far-infrared peak redshifted to the frequency range 353-857 GHz. This colour-selection favours galaxies in the redshift range z = 2-4, which we consider as cold peaks in the cosmic infrared background. With a 4.′5 beam at the four highest frequencies, our sample is expected to include overdensities of galaxies in groups or clusters, lensed galaxies, and chance line-of-sight projections. We perform a dedicated Herschel-SPIRE follow-up of 234 such Planck targets, finding a significant excess of red 350 and 500 μm sources, in comparison to reference SPIRE fields. About 94% of the SPIRE sources in the Planck fields are consistent with being overdensities of galaxies peaking at 350 μm, with 3% peaking at 500 μm, and none peaking at 250 μm. About 3% are candidate lensed systems, all 12 of which have secure spectroscopic confirmations, placing them at redshifts z > 2.2. Only four targets are Galactic cirrus, yielding a success rate in our search strategy for identifying extragalactic sources within the Planck beam of better than 98%. The galaxy overdensities are detected with high significance, half of the sample showing statistical significance above 10σ. The SPIRE photometric redshifts of galaxies in overdensities suggest a peak at z ≃ 2, assuming a single common dust temperature for the sources of Td = 35 K. Under this assumption, we derive an infrared (IR) luminosity for each SPIRE source of about 4 × 1012 L⊙, yielding star formation rates of typically 700 M⊙ yr-1. If the observed overdensities are actual gravitationally-bound structures, the total IR luminosity of all their SPIRE-detected sources peaks at 4 × 1013 L⊙, leading to total star formation rates of perhaps 7 × 103 M⊙yr-1 per overdensity. Taken together, these sources show the signatures of high-z (z > 2) protoclusters of intensively star-forming galaxies. All these observations confirm the uniqueness of our sample compared to reference samples and demonstrate the ability of the all-sky Planck-HFI cold sources to select populations of cosmological and astrophysical interest for structure formation studies.

Large numbers of women undergo antidepressant treatment during pregnancy; however, long-term consequences for their offspring remain largely unknown. Rodents exposed to serotonin transporter (SERT)-inhibiting antidepressants during development show changes in adult emotion-like behavior. These changes have been equated with behavioral alterations arising from genetic reductions in SERT. Both models are highly relevant to humans yet they vary in their time frames of SERT disruption. We find that anxiety-related behavior and, importantly, underlying serotonin neurotransmission diverge between the two models. In mice, constitutive loss of SERT causes life-long increases in anxiety-related behavior and hyperserotonemia. Conversely, early exposure to the antidepressant escitalopram (ESC; Lexapro) results in decreased anxiety-related behavior beginning in adolescence, which is associated with adult serotonin system hypofunction in the ventral hippocampus. Adult behavioral changes resulting from early fluoxetine (Prozac) exposure were different from those of ESC and, although somewhat similar to SERT deficiency, were not associated with changes in hippocampal serotonin transmission in late adulthood. These findings reveal dissimilarities in adult behavior and neurotransmission arising from developmental exposure to different widely prescribed antidepressants that are not recapitulated by genetic SERT insufficiency. Moreover, they support a pivotal role for serotonergic modulation of anxiety-related behavior.

This study evaluated how the proportional area of natural habitat surrounding a vineyard (i.e. landscape diversity) worked in conjunction with crop vigor, cultivar and rootstock selection to influence biological control of the western grape leafhopper (Erythroneura elegantula Osborn). The key natural enemies of E. elegantula are Anagrus erythroneurae S. Trjapitzin & Chiappini and A. daanei Triapitsyn, both of which are likely impacted by changes in landscape diversity due to their reliance on non-crop habitat to successfully overwinter. Additionally, E. elegantula is sensitive to changes in host plant quality which may influence densities on specific cultivars, rootstocks and/or vines with increased vigor. From 2010-2013, data were collected on natural enemy and leafhopper densities, pest parasitism rates and vine vigor from multiple vineyards that represented a continuum of landscape diversity. Early in the season, vineyards in more diverse landscapes had higher Anagrus spp. densities and lower E. elegantula densities, which led to increased parasitism of E. elegantula. Although late season densities of E. elegantula tended to be lower in vineyards with higher early season parasitism rates and lower total petiole nitrogen content, they were also affected by rootstock and cultivar. While diverse landscapes can support higher natural enemy populations, which can lead to increased biological control, leafhopper densities also appear to be mediated by cultivar, rootstock and vine vigor.

This study evaluated how the proportional area of natural habitat surrounding a vineyard (i.e. landscape diversity) worked in conjunction with crop vigor, cultivar and rootstock selection to influence biological control of the western grape leafhopper (Erythroneura elegantula Osborn). The key natural enemies of E. elegantula are Anagrus erythroneurae S. Trjapitzin & Chiappini and A. daanei Triapitsyn, both of which are likely impacted by changes in landscape diversity due to their reliance on non-crop habitat to successfully overwinter. Additionally, E. elegantula is sensitive to changes in host plant quality which may influence densities on specific cultivars, rootstocks and/or vines with increased vigor. From 2010-2013, data were collected on natural enemy and leafhopper densities, pest parasitism rates and vine vigor from multiple vineyards that represented a continuum of landscape diversity. Early in the season, vineyards in more diverse landscapes had higher Anagrus spp. densities and lower E. elegantula densities, which led to increased parasitism of E. elegantula. Although late season densities of E. elegantula tended to be lower in vineyards with higher early season parasitism rates and lower total petiole nitrogen content, they were also affected by rootstock and cultivar. While diverse landscapes can support higher natural enemy populations, which can lead to increased biological control, leafhopper densities also appear to be mediated by cultivar, rootstock and vine vigor.

We study the evolution of the total star formation (SF) activity, total stellar mass (∑M*) and halo occupation distribution (HOD) in massive haloes by using one of the largest X-ray selected sample of galaxy groups with secure spectroscopic identification in the major blank field surveys (ECDFS, CDFN, COSMOS, AEGIS). We provide an accurate measurement of star formation rate (SFR) for the bulk of the star-forming galaxies using very deep mid-infrared Spitzer MIPS and far-infrared Herschel PACS observations. For undetected IR sources, we provide a well-calibrated SFR from spectral energy distribution (SED) fitting. We observe a clear evolution in the level of SF activity in galaxy groups. The total SF activity in the high-redshift groups (0.5 < z < 1.1) is higher with respect to the low-redshift (0.15 < z < 0.5) sample at any mass by 0.8 ± 0.12 dex. A milder difference (0.35 ± 0.1 dex) is observed between the low-redshift bin and the groups at z ~ 0. We show that the level of SF activity is declining more rapidly in the more massive haloes than in the more common lower mass haloes. We do not observe any evolution in the HOD and total stellar mass-halo mass relations in groups. The picture emerging from our findings suggests that the galaxy population in the most massive systems is evolving faster than galaxies in lower mass haloes, consistently with a 'halo downsizing' scenario.

This study describes an interdisciplinary methodology for helping small farmers prepare for climatic variability. We facilitated workshops in the Mixteca Alta region of Oaxaca, Mexico, in which groups of small farmers described how they had adapted to and prepared for past climate challenges. Farmers reported that their cropping systems were changing for multiple reasons: more drought, later rainfall onset, decreased rural labor, and introduced labor-saving technologies. Examination of climate data found that farmers’ climate narratives were largely consistent with the observational record. There have been increases in temperature and rainfall intensity, and an increase in rainfall seasonality that may be perceived as later rainfall onset. Farmers also identified 14 indicators that they subsequently used to evaluate the condition of their agroecosystems. Farmers ranked landscape-scale indicators as more marginal than farmer management or soil quality indicators. From this analysis, farmers proposed strategies to improve the ability of their agroecosystems to cope with climatic variability. Notably, they recognized that social organizing and education are required for landscape-scale indicators to be improved. This outcome suggests that climate change adaptation by small farmers involves much more than just a set of farming practices, but also community action to tackle collective problems.

We investigate the evolution of the star formation rate (SFR)-density relation in the Extended Chandra Deep Field South and the Great Observatories Origin Deep Survey fields up to z ~ 1.6. In addition to the 'traditional method', in which the environment is defined according to a statistical measurement of the local galaxy density, we use a 'dynamical' approach, where galaxies are classified according to three different environment regimes: group, 'filamentlike' and field. Both methods show no evidence of an SFR-density reversal. Moreover, group galaxies show a mean SFR lower than other environments up to z ~ 1, while at earlier epochs group and field galaxies exhibit consistent levels of star formation (SF) activity. We find that processes related to a massive dark matter halo must be dominant in the suppression of the SF below z ~ 1, with respect to purely density-related processes. We confirm this finding by studying the distribution of galaxies in different environments with respect to the so-called main sequence (MS) of star-forming galaxies. Galaxies in both group and 'filament-like' environments preferentially lie below the MS up to z ~ 1, with group galaxies exhibiting lower levels of star-forming activity at a given mass. At z > 1, the star-forming galaxies in groups reside on the MS. Groups exhibit the highest fraction of quiescent galaxies up to z ~ 1, after which group, 'filament-like' and field environments have a similar mix of galaxy types. We conclude that groups are the most efficient locus for SF quenching. Thus, a fundamental difference exists between bound and unbound objects, or between dark matter haloes of different masses. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

We investigate the evolution of the star formation rate (SFR)-density relation in the Extended Chandra Deep Field South and the Great Observatories Origin Deep Survey fields up to z ~ 1.6. In addition to the 'traditional method', in which the environment is defined according to a statistical measurement of the local galaxy density, we use a 'dynamical' approach, where galaxies are classified according to three different environment regimes: group, 'filamentlike' and field. Both methods show no evidence of an SFR-density reversal. Moreover, group galaxies show a mean SFR lower than other environments up to z ~ 1, while at earlier epochs group and field galaxies exhibit consistent levels of star formation (SF) activity. We find that processes related to a massive dark matter halo must be dominant in the suppression of the SF below z ~ 1, with respect to purely density-related processes. We confirm this finding by studying the distribution of galaxies in different environments with respect to the so-called main sequence (MS) of star-forming galaxies. Galaxies in both group and 'filament-like' environments preferentially lie below the MS up to z ~ 1, with group galaxies exhibiting lower levels of star-forming activity at a given mass. At z > 1, the star-forming galaxies in groups reside on the MS. Groups exhibit the highest fraction of quiescent galaxies up to z ~ 1, after which group, 'filament-like' and field environments have a similar mix of galaxy types. We conclude that groups are the most efficient locus for SF quenching. Thus, a fundamental difference exists between bound and unbound objects, or between dark matter haloes of different masses. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

We study the evolution of the total star formation (SF) activity, total stellar mass (∑M*) and halo occupation distribution (HOD) in massive haloes by using one of the largest X-ray selected sample of galaxy groups with secure spectroscopic identification in the major blank field surveys (ECDFS, CDFN, COSMOS, AEGIS). We provide an accurate measurement of star formation rate (SFR) for the bulk of the star-forming galaxies using very deep mid-infrared Spitzer MIPS and far-infrared Herschel PACS observations. For undetected IR sources, we provide a well-calibrated SFR from spectral energy distribution (SED) fitting. We observe a clear evolution in the level of SF activity in galaxy groups. The total SF activity in the high-redshift groups (0.5 < z < 1.1) is higher with respect to the low-redshift (0.15 < z < 0.5) sample at any mass by 0.8 ± 0.12 dex. A milder difference (0.35 ± 0.1 dex) is observed between the low-redshift bin and the groups at z ~ 0. We show that the level of SF activity is declining more rapidly in the more massive haloes than in the more common lower mass haloes. We do not observe any evolution in the HOD and total stellar mass-halo mass relations in groups. The picture emerging from our findings suggests that the galaxy population in the most massive systems is evolving faster than galaxies in lower mass haloes, consistently with a 'halo downsizing' scenario.

Precise self-assembled monolayer chemistries and microfluidic technology are combined to create small-molecule biorecognition arrays. Small-molecule neurotransmitters or precursors are spatially encoded on monolayer-modified substrates. This platform enables multiplexed screening of G-protein-coupled receptors (GPCRs) from complex media via protein-ligand interactions. Preserving access to all epitopes of small molecules is critical for GPCR recognition. The ability to address multiple small molecules on solid substrates and to sort protein mixtures based on specific affinities is a critical step in creating biochips for proteomic applications. © 2013 American Chemical Society.

Precise self-assembled monolayer chemistries and microfluidic technology are combined to create small-molecule biorecognition arrays. Small-molecule neurotransmitters or precursors are spatially encoded on monolayer-modified substrates. This platform enables multiplexed screening of G-protein-coupled receptors (GPCRs) from complex media via protein-ligand interactions. Preserving access to all epitopes of small molecules is critical for GPCR recognition. The ability to address multiple small molecules on solid substrates and to sort protein mixtures based on specific affinities is a critical step in creating biochips for proteomic applications. © 2013 American Chemical Society.

In the local Universe, galaxy properties show a strong dependence on environment. In cluster cores, early-type galaxies dominate, whereas star-forming galaxies are more and more common in the outskirts. At higher redshifts and in somewhat less dense environments (e.g. galaxy groups), the situation is less clear. One open issue is that of whether and how the star formation rate (SFR) of galaxies in groups depends on the distance from the centre of mass. To shed light on this topic, we have built a sample of X-ray selected galaxy groups at 0 < z < 1.6 in various blank fields [Extended Chandra Deep Field South (ECDFS), Cosmological Evolution Survey (COSMOS), Great Observatories Origin Deep Survey (GOODS)]. We use a sample of spectroscopically confirmed group members with stellar mass M* > 1010.3M* in order to have a high spectroscopic completeness. As we use only spectroscopic redshifts, our results are not affected by uncertainties due to projection effects. We use several SFR indicators to link the star formation (SF) activity to the galaxy environment. Taking advantage of the extremely deep mid-infrared Spitzer MIPS and far-infrared Herschel1 PACS observations, we have an accurate, broad-band measure of the SFR for the bulk of the star-forming galaxies. We use multi-wavelength Spectral Energy Distribution (SED) fitting techniques to estimate the stellar. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

In the local Universe, galaxy properties show a strong dependence on environment. In cluster cores, early-type galaxies dominate, whereas star-forming galaxies are more and more common in the outskirts. At higher redshifts and in somewhat less dense environments (e.g. galaxy groups), the situation is less clear. One open issue is that of whether and how the star formation rate (SFR) of galaxies in groups depends on the distance from the centre of mass. To shed light on this topic, we have built a sample of X-ray selected galaxy groups at 0 < z < 1.6 in various blank fields [Extended Chandra Deep Field South (ECDFS), Cosmological Evolution Survey (COSMOS), Great Observatories Origin Deep Survey (GOODS)]. We use a sample of spectroscopically confirmed group members with stellar mass M* > 1010.3M* in order to have a high spectroscopic completeness. As we use only spectroscopic redshifts, our results are not affected by uncertainties due to projection effects. We use several SFR indicators to link the star formation (SF) activity to the galaxy environment. Taking advantage of the extremely deep mid-infrared Spitzer MIPS and far-infrared Herschel1 PACS observations, we have an accurate, broad-band measure of the SFR for the bulk of the star-forming galaxies. We use multi-wavelength Spectral Energy Distribution (SED) fitting techniques to estimate the stellar. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

The healing response of blood vessels from the vascular injury induced by therapeutic interventions is characterized by increased cellularity and tissue remodeling. Frequently, this leads to intimal hyperplasia and lumen narrowing, with significant clinical sequelae. Vascular smooth muscle cells are the primary cell type involved in this process, wherein they express a dedifferentiated phenotype that transiently resembles neoplastic transformation. Recent studies have highlighted the role of mitochondrial proteins, such as the molecular chaperone heat shock protein-90 (Hsp90), in promoting cancer cell survival, which leads to new candidate chemotherapeutic agents for neoplastic disease. Herein, we identify mitochondrial Hsp90 as a key modulator of the vascular injury response. Hsp90 expression is up-regulated in injured arteries and colocalizes with the apoptosis inhibitor, survivin, in vascular smooth muscle cell in vitro and in vivo. By using a proteomic approach, we demonstrate that targeted disruption of mitochondrial Hsp90 chaperone function in vascular smooth muscle cell leads to loss of cytoprotective client proteins (survivin and Akt), induces mitochondrial permeability, and leads to apoptotic cell death. Hsp90 targeting using a cell-permeable peptidomimetic agent resulted in marked attenuation of neointimal lesions in a murine arterial injury model. These findings suggest that mitochondrial Hsp90 chaperone function is an important regulator of intimal hyperplasia and may have implications for molecular strategies that promote the long-term patency of cardiovascular interventions.

The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans.

The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans.

Mid-infrared images of the Seyfert 1 galaxy Mrk 279 obtained with the ISO satellite are presented together with the results of a one-year monitoring campaign of the 2.5-11.7 μm spectrum. Contemporaneous optical photometric and spectrophotometric observations are also presented. The galaxy appears as a point-like source at the resolution of the ISOCAM instrument (4-5″). The 2.5-11.7 μm average spectrum of the nucleus in Mrk 279 shows a strong power law continuum with α = -0.80 ± 0.05 (Fv ∝ vα) and weak PAH emission features. The Mrk 279 spectral energy distribution shows a mid-IR bump, which extends from 2 to 15-20 μm. The mid-IR bump is consistent with thermal emission from dust grains at a distance of ≳ 100 lt-d. No significant variations of the mid-IR flux have been detected during our observing campaign, consistent with the relatively low amplitude (∼10% rms) of the optical variability during the campaign. The time delay for Hβ line emission in response to the optical continuum variations is τ = 16.7-5.6+5.3 days, consistent with previous measurements.

Mid-infrared images of the Seyfert 1 galaxy Mrk 279 obtained with the ISO satellite are presented together with the results of a one-year monitoring campaign of the 2.5-11.7 μm spectrum. Contemporaneous optical photometric and spectrophotometric observations are also presented. The galaxy appears as a point-like source at the resolution of the ISOCAM instrument (4-5″). The 2.5-11.7 μm average spectrum of the nucleus in Mrk 279 shows a strong power law continuum with α = -0.80 ± 0.05 (Fv ∝ vα) and weak PAH emission features. The Mrk 279 spectral energy distribution shows a mid-IR bump, which extends from 2 to 15-20 μm. The mid-IR bump is consistent with thermal emission from dust grains at a distance of ≳ 100 lt-d. No significant variations of the mid-IR flux have been detected during our observing campaign, consistent with the relatively low amplitude (∼10% rms) of the optical variability during the campaign. The time delay for Hβ line emission in response to the optical continuum variations is τ = 16.7-5.6+5.3 days, consistent with previous measurements.

We have reached the end of the history of art, says Arthur Danto. Contemporary arts exist laterally in such a myriad of forms and theories that one can no longer give art's progression a narrative format. Danto's essay, and the discussions that follow it, explores the ramifications of this position. While modernism sought after what art itself is, what it is in its essence, and thus opened up diverse forms of exploration, this alone cannot explain how we got to the state of art as it is now, that of "anything goes." Danto informs us that this "end" of art should not leave us depressed or alarmed, but rather exhilarated, as a "liberation of art beyond history" opens up new possibilities of creation already being implemented in the diverse applications of contemporary artists.