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COPD is the third leading cause of death worldwide, but current therapies for COPD are only effective at treating the symptoms of the disease rather than targeting the underlying pathways that are driving the pathogenic changes. The lack of targeted therapies for COPD is in part due to a lack of knowledge about drivers of disease progression and the difficulty in building relevant and high throughput models that can recapitulate the phenotypic and transcriptomic changes associated with pathogenesis of COPD. To identify these drivers, we have developed a cigarette smoke extract (CSE)-treated bronchosphere assay in 384-well plate format that exhibits CSE-induced decreases in size and increase in luminal secretion of MUC5AC. Transcriptomic changes in CSE-treated bronchospheres resemble changes that occur in human smokers both with and without COPD compared to healthy groups, indicating that this model can capture human smoking signature. To identify new targets, we ran a small molecule compound deck screening with diversity in target mechanisms of action and identified hit compounds that attenuated CSE induced changes, either decreasing spheroid size or increasing secreted mucus. This work provides insight into the utility of this bronchosphere model in examining human respiratory diseases, the pathways implicated by CSE, and compounds with known mechanisms of action for therapeutic development.

Predictive coding is an important candidate theory of self-supervised learning in the brain. Its central idea is that sensory responses result from comparisons between bottom-up inputs and contextual predictions, a process in which rates and synchronization may play distinct roles. We recorded from awake macaque V1 and developed a technique to quantify stimulus predictability for natural images based on self-supervised, generative neural networks. We find that neuronal firing rates were mainly modulated by the contextual predictability of higher-order image features, which correlated strongly with human perceptual similarity judgments. By contrast, V1 gamma (γ)-synchronization increased monotonically with the contextual predictability of low-level image features and emerged exclusively for larger stimuli. Consequently, γ-synchronization was induced by natural images that are highly compressible and low-dimensional. Natural stimuli with low predictability induced prominent, late-onset beta (β)-synchronization, likely reflecting cortical feedback. Our findings reveal distinct roles of synchronization and firing rates in the predictive coding of natural images.

Background: In plants, there is a large diversity of polysaccharides that comprise the cell wall. Each major type of plant cell wall polysaccharide, including cellulose, hemicellulose, and pectin, has distinct structures and functions that contribute to wall mechanics and influence plant morphogenesis. In recent years, pectin modification and valorization has attracted much attention due to its expanding roles of pectin in biomass deconstruction, food science, material science, and environmental remediation. However, pectin utilization has been limited by our incomplete knowledge of pectin structure. Herein, we present a workflow of principles relevant for the characterization of polysaccharide primary structure using nature’s most complex polysaccharide, rhamnogalacturonan-II (RG-II), as a model.Results: We outline how to isolate RG-II from celery and duckweed cell wall material and red wine using chemical or enzymatic treatments coupled with size-exclusion chromatography. From there, we demonstrate the use of mass spectrometry (MS)-based techniques to determine the glycosyl residue and linkage compositions of the intact RG II molecule and RG-II-derived oligosaccharides including special considerations for labile monosaccharides. In doing so, we demonstrated that in the duckweed Wolffiella repanda the arabinopyranosyl (Arap) residue of side chain B is substituted at O-2 with rhamnose. As RG-II is further modified by non-glycosyl modifications including methyl-ethers, methyl-esters, and acetyl-esters, we then describe ways to use electrospray-MS to identify these moieties on RG-II-derived oligosaccharides. We then explored the utility of proton nuclear magnetic resonance spectroscopy (1H-NMR) in identifying RG-II-specific sugars and non-glycosyl modifications to complement and extend MS-based approaches. Finally, we describe how to assess the factors that affect RG-35 II dimerization using liquid chromatographic and NMR spectroscopic approaches.Conclusions: The complexity of pectic polysaccharide structures has hampered efforts aimed at their valorization. In this work, we used RG-II as a model to demonstrate the steps necessary to isolate and characterize polysaccharides using chromatographic, MS, and NMR techniques. The principles can be applied to the characterization of other saccharide structures and will help inform researchers on how saccharide structure relates to functional properties in the future.

Predictive coding is an important candidate theory of self-supervised learning in the brain. Its central idea is that neural activity results from an integration and comparison of bottom-up inputs with contextual predictions, a process in which firing rates and synchronization may play distinct roles. Here, we quantified stimulus predictability for natural images based on self-supervised, generative neural networks. When the precise pixel structure of a stimulus falling into the V1 receptive field (RF) was predicted by the spatial context, V1 exhibited characteristic γ-synchronization (30-80Hz), despite no detectable modulation of firing rates. In contrast to γ, β-synchronization emerged exclusively for unpredictable stimuli. Natural images with high structural predictability were characterized by high compressibility and low dimensionality. Yet, perceptual similarity was mainly determined by higher-level features of natural stimuli, not by the precise pixel structure. When higher-level features of the stimulus in the receptive field were predicted by the context, neurons showed a strong reduction in firing rates and an increase in surround suppression that was dissociated from synchronization patterns. These findings reveal distinct roles of synchronization and firing rates in the predictive coding of natural images.

Out of nearly 30,000 teleosts dwelling in our planet’s water bodies, only hundreds of them are commercially exploited and prevail on the global food market. Yet, our estimates of the species actually underpinning global trade is severely hampered by inaccuracy and non-compliance in labelling and reporting. Here, we target ethnic food stores in two British cities (Liverpool and Manchester metropolitan areas), whose numbers are increasing throughout Europe, to examine accuracy of traceability information available to consumers. Despite the existence of thorough EU labelling regulations, we unveil a high level of non-compliance, with a diverse range of poorly-known fish species, often sold without any label, or with erroneous information, as demonstrated by DNA barcoding. Results indicate that about 41% of the samples were mislabelled, in stark contrast with a recent study that, in 2015, found less than 5% mislabelling in EU supermarkets and fishmongers. These results highlight that inspectors and governments might not be fully aware of the wide diversity of fish species traded, indicating the need for a stronger enforcement of the EU labelling legislations. Compliance with regulations is required not only to protect consumers, but also fish stocks, as for many of the species identified in this survey, population assessment is poor or lacking altogether.

The integration of direct bottom-up inputs with contextual information is a canonical motif in neocortical circuits. In area V1, neurons may reduce their firing rates when the (classical) receptive field input can be predicted by the spatial context. We previously hypothesized that gamma-synchronization (30-80Hz) provides a complementary signal to rates, encoding whether stimuli are predicted from spatial context by preferentially synchronizing neuronal populations receiving predictable inputs. Here we investigated how rates and synchrony are modulated by predictive context. Large uniform surfaces, which have high spatial predictability, strongly suppressed firing yet induced prominent gamma-synchronization, but only when they were colored. Yet, chromatic mismatches between center and surround, breaking predictability, strongly reduced gamma-synchronization while increasing firing rates. Differences between colors, including strong gamma-responses to red, arose because of stimulus adaptation to a full-screen background, with a prominent difference in adaptation between M- and L-cone signaling pathways. Thus, synchrony signals whether RF inputs are predicted from spatial context and may encode relationships across space, while firing rates increase when stimuli are unpredicted from the context.

The oil and gas industry has become increasingly focused on cost reducing technologies. Processing and treating systems used to monetize resources can often be heavy and require a large footprint. When operating in challenging locations, such as deep water or the arctic, these systems can be very expensive. To address these challenges, a novel adsorption-based gas separation technology platform has been under development for process intensification. This technology uses rapid pressure- and/or temperature-swing cycles to dramatically reduce equipment size and weight, and overall gas treating footprint by ~50%, relative to conventional technologies. In addition to CAPEX savings, the weight and footprint savings are beneficial in locations where space is at a premium. Furthermore, the technology is well suited for skid-based deployment, which provides execution efficiencies. While the technology platform is broadly applicable for a variety of Upstream gas separations, the current focus of development has been on deep dehydration and CO2 removal before cryogenic gas processes, such as LNG or NGL recovery. Extensive fundamental research, including laboratory and pilot testing, has been completed to demonstrate technical feasibility. Construction of a field research and demonstration facility is underway to demonstrate scaled-up operation over a wide range of operating conditions. This paper will provide background on the technology platform, the key enablers, the scale-up approach, and integration in an LNG process.

Since launch, the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments on the Terra and Aqua spacecraft have operated successfully for more than 14 and 12 years, respectively. A key instrument for National Aeronautics and Space Administration Earth Observing System missions, MODIS was designed to make continuous observations for studies of Earth's land, ocean, and atmospheric properties and to extend existing data records from heritage Earth observing sensors. The 16 thermal emissive bands (TEBs) (3.75–14.24 $\mu\mbox{m} $ ) are calibrated on orbit using a temperature controlled blackbody (BB) . Both Terra and Aqua MODIS BBs have displayed minimal drift over the mission lifetime, and the seasonal variations of the BB temperature are extremely small in Aqua MODIS. The long-term gain and noise equivalent difference in temperature performance of the 160 TEB detectors on both MODIS instruments have been well behaved and generally very stable. Small but noticeable variations of Aqua MODIS bands 33–36 (13.34–14.24 $\mu\mbox{m} $ ) response in recent years are primarily due to loss of temperature control margin of its passive cryoradiative cooler. As a result, fixed calibration coefficients, previously used by bands when the BB temperature is above their saturation temperatures, are replaced by the focal-plane-temperature-dependent calibration coefficients. This paper presents an overview of the MODIS TEB calibration, the on-orbit performance, and the challenging issues likely to impact the instruments as they continue operating well past their designed lifetime of six years.

This paper presents a way to enhance student interest and learning when teaching economic inequality. The approach draws on a well-known survey conducted by Norton and Ariely (2011). The approach involves surveying students, asking them to estimate the current level of wealth inequality in the US, and asking them to state their ideal level of wealth inequality. As in Norton and Ariely’s survey of a representative sample of Americans, our students underestimated actual wealth inequality and preferred a distribution of wealth for the US that was more equal than any country’s distribution. We suggest ways the student survey results can be presented and discussed. We also provide Stata code and an Excel workbook to ease effective classroom presentation of the survey results. This approach to beginning the study of inequality piqued our students’ interest and helped them understand how inequality is measured.

Disease knowledge is an important component of medication self-management. We examined HIV knowledge and understanding among 166 HIV-infected 13- to 21-year-olds (53% female, 72.9% African American, 59.6% perinatally infected). Behaviorally infected youth outperformed perinatally infected youth on HIV transmission knowledge and were more likely to report provider discussions about getting condoms and how drugs impair sexual decision making. While youth accurately answered most (78%) true/false questions, many could not define resistance (71.0%), viral load (59.0%), or CD4 (43.4%). Only 29.5% reported knowing either their CD4 count or viral load. Provider discussions about biomarkers likely contribute to greater HIV knowledge and understanding, especially for youth with lower CD4 counts, perhaps because illness triggers extended provider discussions.

Secondary prevention programs are needed to help HIV-positive youth reduce risk behavior and improve adherence to HIV medications. This article provides an overview of Adolescent Impact, a secondary HIV prevention intervention, including its description, delivery, and receptivity among the two unique groups of participants. Adolescent Impact, a 12-session behavioral intervention incorporating individual and group components was designed to increase HIV knowledge, disease management and risk reduction skills, and motivate healthy lifestyles among HIV-infected adolescents. A standardized protocol was implemented at three sites in the northeastern United States. One hundred sixty-six HIV-positive youth, aged 13-21 (mean = 16.8 years), enrolled in the study were randomized to receive either the intervention (n = 83) or standard of care (n = 83). Participants were predominantly of minority race/ethnicity (94% African American or Hispanic); 53% were female and 59.6% were perinatally infected. Perinatally infected youth were significantly more likely to be young, had experienced HIV Class C-related symptoms and had CD4-positive T lymphocyte counts of fewer than 200 cells (all p values < .01). The mean number of sessions attended was 9.4, with most (83.3%) participants attending at least half (≥ 6) of the intervention sessions (86% perinatally infected, 78.6% behaviorally infected, p = .5). Participants' sociodemographic and clinical characteristics mirrored those of the larger HIV adolescent cohort in the United States Relatively high attendance rates suggest that youth were receptive to the program and its content. Through use of multiple intervention modalities, Adolescent Impact was able to accommodate a diverse group of clinic-attending HIV-positive youth and address the need for a compact intervention for use in the clinical setting.

This study examined the nature, type, and source of social support available to a diverse group of HIV-infected adolescents and the relationship between social support and depression. Data were obtained from the baseline assessment of Adolescent Impact, a behavioral intervention conducted in 2003-2006 involving 166 HIV-infected youth, ages 13-21, in care at four urban medical centers. Youth completed the Medical Outcomes Study Social Support Survey, Beck Depression Inventory, and questions about HIV-specific social support including locus (family and friends) and type (structural, perceived, instrumental, and satisfaction). Linear regression modeling examined the relation between HIV-specific and general perceived social support, and between social support and depression. Participants were predominately minority (72% black and 20% Hispanic); perinatally infected (60% PIY), and female (53%). Most had someone to either remind them to attend (71%) or to bring them to clinic (60%), a majority family (53%) and fewer friends (4%). More youth reported being satisfied with family (64%) social support than that from friends (51%). Behaviorally infected youth (BIY) had significantly more friends who knew their serostatus than PIY (means = 4.5 and 1.7; p < 0.001), but received significantly less help from family in accessing care (p < 0.001). Satisfaction with family social support was the best predictor of general perceived social support with general perceived social support and behavioral mode of transmission the best predictors of depression. Regular screening of HIV-positive youth for social support needs, especially BIY, and identification of sources for social support should be a regular part of care.

Making sense of Labour Force Survey response ratesThe Labour Force Survey (LFS) is thelargest continuous household surveyin the UK. It is the source of key labourmarket indicators, such as employment,unemployment, economic activity andhours worked, as well as numerousrelated measures. Each quarter, morethan 80,000 households are randomlyselected; households and individuals areinterviewed in a series of fi ve quarterlywaves. However, a proportion of thesehouseholds and individuals either cannotbe contacted or refuse to cooperate withthe survey, so the results are derived fromabout 50,000 households and 120,000individuals each quarter. These responsesare weighted on the basis of age, genderand geography in order to produce arepresentative picture of the wholepopulation.This article presents and analyses LFSresponse rates and trends and examinesthe detail of response and non-response.Further research required and potentialinterventions are also discussed.

Two nearly identical Moderate Resolution Imaging Spectroradiometer (MODIS) sensors, one on the Terra and the other on the Aqua satellite, are currently operating in space, making continuous global observations in 36 spectral bands: 20 reflective solar bands (RSBs) and 16 thermal emissive bands. For MODIS RSB with wavelengths from 0.41 to 2.1 mum, the sensor-specified calibration-accuracy requirements are plusmn2% for reflectance and plusmn5% for radiance products. They are calibrated on-orbit by a solar diffuser (SD) and an SD stability monitor. In addition, lunar observations are scheduled regularly to monitor the RSB radiometric calibration stability. This letter describes an intercomparison method developed for evaluating the calibration consistency between Terra and Aqua MODIS RSBs and calibration differences among detectors in each spectral band. It presents intercomparison results derived from Terra and Aqua MODIS lunar observations made over their overlapped mission operation. This method uses predicted lunar irradiances derived from a lunar model to remove lunar-viewing-geometry differences among different observations made by each sensor. The results, excluding the bands which either have electronic crosstalk or saturate during lunar observations, show that the Terra and Aqua MODIS RSBs have been consistently calibrated to within plusmn1%. For the detectors within any one spectral band, the calibration differences are less than plusmn0.5%. The methodology developed here can be applied to other sensors for intercomparison studies.

This report describes MaRIE experimental facility in the November 2015 issue of their Science and Technology newsletter.

Los Alamos National Laboratory (LANL) hosted the Stewardship Science Academic Programs Symposium, which is designed to foster relationships among young scientists, sponsors and the National Nuclear Security Administration national laboratories. The event highlights much of the work done by prominent scientists and allows attendees to view the multiple on site facilities at LANL.

At the request of Katherine Richardson-McDaniel, Staff Member to U.S. Senator Martin Heinrich (D-NM), a high-level briefing was requested about MaRIE 1.0, the Matter-Radiation Interactions in Extremes effort at Los Alamos National Laboratory. What it would be, the mission need motivation, the scientific challenge, and the current favorable impact on both programs and people are shown in viewgraph form.

To meet new and emerging national security issues the Laboratory is stepping up to meet another grand challenge—transitioning from observing to controlling a material’s performance. This challenge requires the best of experiment, modeling, simulation, and computational tools. MaRIE is the Laboratory’s proposed flagship experimental facility intended to meet the challenge.

After the decision to end nuclear testing and the inception of the Stockpile Stewardship program, the condition of the stockpile was the primary mission driver. During the first two decades of stewardship, the primary program goal could be described as underwriting the Stockpile-to-Target Sequence (STS), the military requirements on the conditions the nuclear warheads needed to survive and still operate.

John Caldwell, president of Kio-Tek (KT), presents his company's business plan to a group of 30 venture capitalists at the November 2001 annual meeting of the Portland Venture Group. John's presentation is included in the case as an exhibit. The case begins with a brief overview of the meeting and John's presentation. The body of the case describes the question and answer period immediately following John's presentation.Included in the case is a set of exhibits that John has handed out to the audience as supplemental information. These exhibits provide additional information on marketing, management, and financial issues facing the company and John refers to them throughout the question and answer period. The VC's ask John a variety of questions in an effort to determine whether KT is an attractive investment opportunity

(2004). Old Habits Die Hard:Path Dependency and Behavioral Lock-in. Journal of Economic Issues: Vol. 38, Papers From The 2004 AFEE Meeting, pp. 371-377.

Background Most studies of political conflict rely on imported measures of mental health. We identified and tested a local definition of suffering in the occupied Palestinian territory that we labelled "Feeling Broken or Destroyed". Methods The construct was identified in group interviews completed in Arabic in 2010, with 68 residents as the total sample size from the West Bank, East Jerusalem, and the Gaza Strip aged 30–40 years. Survey items were then written and given to a representative sample of people (same age group in the same territories) in June 2011 (n=508; study 1), and November 2011 (n=1778; study 2). All data were collected with written consent by the Palestinian Center for Policy and Survey Research, who purposively selected participants to represent key elements of diversity in Palestinian society. Findings Participants referred in Arabic to a type of suffering not included in standard instruments, which the participants typically associated with economic and political hardships. Descriptions from the participants included being or feeling: broken, crushed (muḥaṭṭima), destroyed, (mudammira), exhausted, and tired (ta'bāna). Aspects of the participants were described as the self or spirit (an-nafs), morale (al-ma'naūiyyat), and hopes or ambition for the future (amālak aū ṭamūḥatak ban-nisba lil-mustaqbil). The following survey items were then written in English, translated to Arabic, and back-translated. The survey was administered in Arabic, asking the respondents to rate how often during the past 2 weeks they "felt that your spirit or morale is broken or destroyed?" (Kam murra aḥsast ba'n nasfiyyatak wa ma'naūiyyatak muḥaṭṭima?); "felt that your ambitions and hopes for the future are destroyed?" (Kam murra aḥsast ba'n amālak aū ṭamūḥatak ban-nisba lil-mustaqbil muḥaṭṭima?); and "felt emotionally or psychologically exhausted?" (Kam murra aḥsast ba'nak murhaq ‘āṭafiyyan aū nafsiyyan?). Internal consistency of these items across subgroups in studies 1 and 2 ranged from 0·80 to 0·87. Discriminant validity was evident in that these items factored separately from standard mental health items in principal components analysis. The scale correlated moderately in both data sets with: feelings of depression (study 1: r =0·46; p r =0·55; p r =0·21; p r =0·21; p Interpretation Contextualised suffering can be discerned through careful interviewing, and can be efficiently and reliably measured, tested, and quantitatively distinguished from traditional mental health measures. Funding The Jacobs Foundation, Switzerland.

Purpose This mixed-methods exploratory study identified and then developed and validated a quantitative measure of a new construct of mental suffering in the occupied Palestinian territory: feeling broken or destroyed. Methods Group interviews were conducted in 2011 with 68 Palestinians, most aged 30–40, in the West Bank, East Jerusalem, and the Gaza Strip to discern local definitions of functioning. Interview participants articulated of a type of suffering not captured in existing mental health instruments used in regions of political conflict. In contrast to the specific difficulties measured by depression and PTSD (sleep, appetite, energy, flashbacks, avoidance, etc.), participants elaborated a more existential form of mental suffering: feeling that one’s spirit, morale and/or future was broken or destroyed, and emotional and psychological exhaustion. Participants articulated these feelings when describing the rigors of the political and economic contexts in which they live. We wrote survey items to capture these sentiments and administered these items—along with standard survey measures of mental health—to a representative sample of 1,778 32–43 year olds in the occupied Palestinian territory. The same survey questions also were administered to a representative subsample (n = 508) six months earlier, providing repeated measures of the construct. Results Across samples and time, the feeling broken or destroyed scale: 1) comprised a separate factor in exploratory factor analyses, 2) had high inter-item consistency, 3) was reported by both genders and in all regions, 4) showed discriminate validity via moderate correlations with measures of feelings of depression and trauma-related stress, and 5) was more commonly experienced than either feelings of depression or trauma-related stress. Conclusions Feeling broken or destroyed can be reliably measured and distinguished from conventional measures of mental health. Such locally grounded and contextualized measures should be identified and included in assessments of the full impact of protracted political conflict on functioning.

We previously isolated a pollen-specific gene encoding a pollen tube wall-associated glycoprotein with a globular domain and an extensin domain from maize (mPex1). To evaluate which protein domains might be important for function, we isolated a second monocot gene (mPex2) and a dicot gene (tPex). Each gene encodes a signal sequence, an N-terminal globular domain comprised of a variable region, a leucine-rich repeat (LRR) with an adjacent cysteine-rich region, a transition region and an extensin-like C-terminal domain. The LRRs of the maize and tomato Pex proteins are highly conserved. Although the extensin domains in the maize and tomato proteins vary in length and in amino acid sequence, they are likely to be structurally conserved. Additional putative Pex gene sequences were identified by either GenBank search (Arabidopsis) or PCR (sorghum and potato); all encode conserved LRRs. The presence of a conserved LRR in the known and potential Pex proteins strongly suggests that this motif is involved in the binding of a specific ligand during pollen tube growth. Gene expression studies using RNA and protein blotting as well as promoter-reporter gene fusions in transient and stable transformation indicate that the tomato Pex gene is pollen-specific.