Intrinsic Dimensionality as a Metric for the Impact of Mission Design Parameters.

High-resolution space-based spectral imaging of the Earth's surface delivers critical information for monitoring changes in the Earth system as well as resource management and utilization. Orbiting spectrometers are built according to multiple design parameters, including ground sampling distance (GSD), spectral resolution, temporal resolution, and signal-to-noise ratio. Different applications drive divergent instrument designs, so optimization for wide-reaching missions is complex. The Surface Biology and Geology component of NASA's Earth System Observatory addresses science questions and meets applications needs across diverse fields, including terrestrial and aquatic ecosystems, natural disasters, and the cryosphere. The algorithms required to generate the geophysical variables from the observed spectral imagery each have their own inherent dependencies and sensitivities, and weighting these objectively is challenging. Here, we introduce intrinsic dimensionality (ID), a measure of information content, as an applications-agnostic, data-driven metric to quantify performance sensitivity to various design parameters. ID is computed through the analysis of the eigenvalues of the image covariance matrix, and can be thought of as the number of significant principal components. This metric is extremely powerful for quantifying the information content in high-dimensional data, such as spectrally resolved radiances and their changes over space and time. We find that the ID decreases for coarser GSD, decreased spectral resolution and range, less frequent acquisitions, and lower signal-to-noise levels. This decrease in information content has implications for all derived products. ID is simple to compute, providing a single quantitative standard to evaluate combinations of design parameters, irrespective of higher-level algorithms, products, applications, or disciplines.

Deposition of PFAS 'forever chemicals' on Mt. Everest.

Mt. Everest, one of the most coveted climbing mountains on earth, also contains the highest altitude chemical contamination on land. For the first time, meltwater and snow samples from Mt. Everest's Khumbu Glacier were analyzed for "forever chemicals" per- and polyfluoroalkyl substances (PFAS). Our research team utilized solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify pollutants sampled from Everest Base Camp, Camp 1, Camp 2, and Everest Balcony. From the 14 PFAS compounds tested for, we found perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexanoic acid (PFHxA) in Mt. Everest snow and meltwater. The highest concentrations found were 26.14 ng/L and 10.34 ng/L PFOS at Base Camp and Camp 2, respectively. However, PFAS species were seen within 1-2 orders of magnitude in all sampling sites with detection, potentially suggesting a widespread presence on the mountain. Our samples are the highest altitude PFAS samples ever retrieved and indicate the need for further sampling both on Mt. Everest and in the below-glacier watershed.

Generation of goats by nuclear transfer: a retrospective analysis of a commercial operation (1998-2010).

At LFB USA, Inc., the ultimate use for transgenic cloned goats is for the production of recombinant human protein therapeutics in their milk. This retrospective analysis of the Somatic Cell Nuclear Transfer (SCNT) program, spanning from 1998 to 2010, examined parameters potentially affecting the outcomes and efficiencies in this commercial operation. Over 37,000 + ova were utilized in the SCNT protocol producing a total of 203 cloned goats. Fifty one (51) clones were produced from non-transfected (transgenic and non-transgenic animal donor) cell lines and 152 clones were produced from transfected cell lines. Comparisons and summaries of (a) transfected versus non-transfected cell lines, (b) relationship of SCNT parameters to offspring produced, (c) skin versus fetal cells, (d) fresh versus cryopreserved cells, (e) parameters from all cell lines used versus those producing SCNT offspring, (f) variation among cell sources, (g) methods of SCNT parturition management and effects on live offspring, and lastly (h) SCNT variation by program are reported. Findings indicate that (a) non-transfected cell lines were more efficient versus transfected cell lines in generating viable cloned offspring on a per reconstructed embryo transferred basis, (b) transfected fetal fibroblasts had improved efficiency versus transfected skin fibroblasts, (c) the percentage of non-transfected cell lines that produced offspring was statistically higher than transfected cell lines, (d) and induction of parturition improved the percentage of viable offspring. In summary, this retrospective analysis on the SCNT process has identified certain parameters for improved efficiency in producing viable cloned goats in a commercial setting.

A screening-level approach to quantifying risk from glacial release of organochlorine pollutants in the Alaskan Arctic.

Widespread distribution of atmospherically mobilized organochlorine pollutants (OCPs) has been documented throughout the Arctic. A fraction of these OCPs have become entrained in glacial ice, and during melting, they can be released into downstream reservoirs. Though this remobilization is known, an assessment of risk from glacial meltwater to collocated human communities in the Arctic, including Alaska, had not been accomplished. Here, we use a screening-level risk assessment model for glacial watersheds, based on US Environmental Protection Agency (EPA) methodology, which we apply to the glaciated Jarvis Creek watershed of interior Alaska. Model results indicate that even with low levels of OCPs in glacial meltwater, high fish consumption by subsistence communities in the area increases the risk of cancer and hazard impacts above acceptable limits. Though this model is specific to one watershed, our results imply that further investigation of an increasing OCP signal in glacial meltwater and fish throughout the North American Arctic is warranted.

Quantitative screening level assessment of human risk from PCBs released in glacial meltwater: Silvretta Glacier, Swiss Alps.

Persistent organic pollutants (POPs) are entrained within glaciers globally, reemerging in many alpine ecosystems. Despite available data on POP flux from glaciers, a study of human health risk caused by POPs released in glacial meltwater has never been attempted. Glaciers in the European Alps house the largest known quantity of POPs in the Northern Hemisphere, presenting an opportunity for identification of potential risk in an endmember scenario case study. With methodology developed by the US Environmental Protection Agency (EPA), we provide a regional screening level human risk analysis of one class of POPs, polychlorinated-biphenyls (PCB) that have been measured in melt waters from the Silvretta Glacier in the Swiss Alps. Our model suggests the potential for both cancer and non-cancer impacts in residents with lifetime exposure to current levels of PCB in glacial meltwater and average consumption of local fish. For residents with an abbreviated 30-year exposure timeframe, the risk for cancer and non-cancer impacts is low. Populations that consume higher quantities of local fish are predicted to be at a greater risk, with risk to lifetime consumers higher by an order of magnitude. Based on the results of our screening study, we suggest that local government move to the next step within the risk assessment framework: local monitoring and management. Within the Alps, other glacial watersheds of a similar size and latitude may see comparable risk and our model framework can be adapted for further implementation therein.

Generation of transgenic goats by pronuclear microinjection: a retrospective analysis of a commercial operation (1995-2012).

Production of transgenic founder goats involves introducing and stably integrating an engineered piece of DNA into the genome of the animal. At LFB USA, the ultimate use of these transgenic goats is for the production of recombinant human protein therapeutics in the milk of these dairy animals. The transgene or construct typically links a milk protein specific promoter sequence, the coding sequence for the gene of interest, and the necessary downstream regulatory sequences thereby directing expression of the recombinant protein in the milk during the lactation period. Over the time period indicated (1995-2012), pronuclear microinjection was used in a number of programs to insert transgenes into 18,120, 1- or 2- cell stage fertilized embryos. These embryos were transferred into 4180 synchronized recipient females with 1934 (47%) recipients becoming pregnant, 2594 offspring generated, and a 109 (4.2%) of those offspring determined to be transgenic. Even with new and improving genome editing tools now available, pronuclear microinjection is still the predominant and proven technology used in this commercial setting supporting regulatory filings and market authorizations when producing founder transgenic animals with large transgenes (> 10 kb) such as those necessary for directing monoclonal antibody production in milk.

Control of microbial sulfide production by limiting sulfate dispersal in a water-injected oil field.

Oil production by water injection often involves the use of makeup water to replace produced oil. Sulfate in makeup water is reduced by sulfate-reducing bacteria to sulfide, a process referred to as souring. In the MHGC field souring was caused by using makeup water with 4mM (384ppm) sulfate. Mixing with sulfate-free produced water gave injection water with 0.8mM sulfate. This was amended with nitrate to limit souring and was then distributed fieldwide. The start-up of an enhanced-oil-recovery pilot caused all sulfate-containing makeup water to be used for dissolution of polymer, which was then injected into a limited region of the field. Produced water from this pilot contained 10% of the injected sulfate concentration as sulfide, but was free of sulfate. Its use as makeup water in the main water plant of the field caused injection water sulfate to drop to zero. This in turn strongly decreased produced sulfide concentrations throughout the field and allowed a decreased injection of nitrate. The decreased injection of sulfate and nitrate caused major changes in the microbial community of produced waters. Limiting sulfate dispersal into a reservoir, which acts as a sulfate-removing biofilter, is thus a powerful method to decrease souring.

Legacy organochlorine pollutants in glacial watersheds: a review.

Northern Hemisphere alpine glaciers have been identified as a point of concentration and reemergence of legacy organochlorine pollutants (OCPs). In this review, we compile a selection of published literature combining long-range, global atmospheric transport and distribution-based compartmental environmental flux models, as well as data from glacial meltwater, ice core, crevasse and proglacial lake sediment studies. Regional studies of ice and meltwater in alpine glaciers of the northern latitudes show similarities in sample deposition profiles and concentration due to chemical atmospheric residence time, precipitation type and glacier flow rates. In glaciated locations near areas of extensive OCPs use, such as the Swiss and Italian Alps, glacier sample concentrations are higher, while in areas more distant from use, including Arctic nations, OCPs concentrations in glaciers are significantly lower. Our review identifies alpine glaciers co-located with regions characterized by OCPs use as a significant organochlorine pollutant distribution source, secondary in timing and location to direct deposition, with subsequent bioaccumulation and potential human risk impacts.

Long-term life quality and family needs after traumatic brain injury.

OBJECTIVES: This investigation assessed the life quality and long-term family needs of caregivers of persons with brain injury. DESIGN: Respondents completed the Virginia Traumatic Brain Injury Family Needs Assessment Survey. SETTING: Community-based sample. PARTICIPANTS: Respondents included 57 caregivers of persons with traumatic brain injury who were at least 4 years after injury and who resided in Virginia. Respondents ranged in age from 19 to 82 years and were primarily women and Caucasian. OUTCOME MEASURES: The Family Needs Questionnaire (FNQ) and quality of life questions. RESULTS: Results indicate diminished life quality after injury. With regard to family needs, Health Information (51.43%) and Involvement with Care (47.93%) needs were most often rated as met. Instrumental Support (31.52%) and Professional Support (28.38%) needs were most often rated as not met. CONCLUSIONS: Family needs and support systems for those needs change over time. This investigation provides evidence that unmet family needs extend well beyond the acute setting and that caregiver life quality diminishes over time. The importance of appreciating long-term family needs and other life quality issues should not be underestimated.

Partnership for front-line success: a call for a national action agenda on workforce development.

Despite more than a decade of dialogue on the critical needs and challenges in public health workforce development, progress remains slow in implementing recommended actions. A life-long learning system for public health remains elusive. The Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry in collaboration with other partners in federal, state, local agencies, associations and academia is preparing a national action agenda to address front-line preparedness. Four areas of convergence have emerged regarding: (1) the use of basic and crosscutting public health competencies to develop practice-focused curricula; (2) a framework for certification and credentialing; (3) the need to establish a strong science base for workforce issues; and (4) the acceleration of the use of technology-supported learning in public health.

The CEFP. Implications for public health education and training.

The 300-year history of the American academy outlines many of the contemporary pressures that are shaping the modern university. Faculty members need to balance the expectations of teaching, research, and service to amass a dossier that will lead to tenure. The academy needs to offer curricula that prepare graduates to enter the work force. Administrators need to encourage strong community ties to convince benefactors to invest in the renovation and expansion of university facilities. These pressures are especially acute in academic public health. The public health research agenda has extended from the study of infectious disease into behavioral risk and chronic disease. Schools of public health struggle to link curriculum, research, and service that will educate students, advance scholarship, and develop community interaction for the prevention of disease and the promotion of health. The Collaborative Evaluation Fellows Project provides a mechanism for the convergence and resolution of these pressures facing schools of public health.

Characterization of a new human B7-related protein: B7RP-1 is the ligand to the co-stimulatory protein ICOS.

Optimal T cell activation requires the interactions of co-stimulatory molecules, such as those in the CD28 and B7 protein families. Recently, we described the co-stimulatory properties of the murine ligand to ICOS, which we designated as B7RP-1. Here, we report the co-stimulation of human T cells through the human B7RP-1 and ICOS interaction. This ligand-receptor pair interacts with a K:(D) approximately 33 nM and an off-rate with a t((1/2)) > 10 min. Interestingly, tumor necrosis factor (TNF)-alpha differentially regulates the expression of human B7RP-1 on B cells, monocytes and dendritic cells (DC). TNF-alpha enhances B7RP-1 expression on B cells and monocytes, while it inhibits it on DC. The human B7RP-1-Fc protein or cells that express membrane-bound B7RP-1 co-stimulate T cell proliferation in vitro. Specific cytokines, such as IFN-gamma and IL-10, are induced by B7RP-1 co-stimulation. Although IL-2 levels are not significantly increased, B7RP-1 co-stimulation is dependent on IL-2. These experiments define the human ortholog to murine B7RP-1 and characterize its interaction with human ICOS.

TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation.

We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand family that is functionally involved in B cell proliferation. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune disease. Here, we describe expression cloning of a cell surface receptor for TALL-1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is identical to the previously reported TNF receptor (TNFR) homologue transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human and murine TACI share 54% identity overall. Human TACI exhibits high binding affinities to both human and murine TALL-1. Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In addition, when injected into mice, soluble TACI inhibits antibody production to both T cell-dependent and -independent antigens. By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation. The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus.

Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice.

TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TNF) ligand superfamily that is functionally involved in B cell proliferation. Here, we describe B cell hyperplasia and autoimmune lupus-like changes in transgenic mice expressing TALL-1 under the control of a beta-actin promoter. The TALL-1 transgenic mice showed severe enlargement of spleen, lymph nodes, and Peyer's patches because of an increased number of B220+ cells. The transgenic mice also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE. In addition, a phenotype similar to autoimmune lupus-like disease was also seen in TALL-1 transgenic mice, characterized by the presence of autoantibodies to nuclear antigens and immune complex deposits in the kidney. Prolonged survival and hyperactivity of transgenic B cells may contribute to the autoimmune lupus-like phenotype in these animals. Our studies further confirm TALL-1 as a stimulator of B cells that affect Ig production. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmune diseases.

Co-stimulation of antigen-specific CD4 T cells by 4-1BB ligand.

4-1BB is a member of the TNF receptor family predominantly expressed on activated T cells, and binds an inducible ligand found on B cells, macrophages and dendritic cells. Whereas ligation of 4-1BB has been shown to enhance response of purified CD8 T cells to mitogens, and to augment NK activity and generation of cytotoxic T lymphocytes in vivo, there are little direct data on 4-1BB action during CD4 responses. Using pigeon cytochrome c-presenting fibroblast antigen-presenting cells transfected with 4-1BB ligand (4-1BBL), we show that engaging 4-1BB on naive CD4 cells promotes proliferation, cell cycle progression and IL-2 secretion, and suppresses cell death, all to a similar extent as B7-1 engagement of CD28. In addition, 4-1BBL synergizes with B7 and ICAM to enhance naive CD4 proliferation when antigen is limiting. 4-1BBL alone, and to a greater extent with B7, also augmented IL-2 secretion resting antigen-experienced CD4 cells, as typified by T helper clones, whereas short-term effector cells showed similar levels of proliferation and cytokine secretion regardless of whether 4-1BB was engaged. A major role in augmenting IFN-gamma, IL-4 or IL-5 was not demonstrated. Blocking studies with activated B cells presenting antigen showed that 4-1BB participates in promoting IL-2 production by resting CD4 cells, confirming that 4-1BBL can play a role in antigen-specific CD4 T cell responses.

Validation of the Service Obstacles Scale for the traumatic brain injury population.

Traumatic brain injury is a leading cause of death and disability in the United States. Limited access to specialized medical and rehabilitation services has been linked to poor outcomes. Literature provides little guidance for assessment of service obstacles and satisfaction with community resources. The present investigation describes the development of a specialized scale to evaluate caregivers' perceptions of brain injury services in the community. Results indicate good internal consistency and criterion-related validity of the Service Obstacles Scale. Lack of money for services and lack of adequate community resources were the greatest concerns voiced by respondents, while lack of transportation was the least problematic. Comparisons are made with regard to family needs and respondents' post-injury life quality. Implications for future research are discussed.

Predicting breast-feeding intention among low-income pregnant women: a comparison of two theoretical models.

This study examined the applicability of the transtheoretical model and a model derived from the theory of reasoned action for predicting breast-feeding intention among low-income pregnant women. Participants completed a 70-item self-report questionnaire assessing their breast-feeding attitudes, intentions, and support. A positive correlation existed between Stages of Change for breast-feeding and the number of Processes of Change used by respondents. A negative correlation existed between Stages of Change for breast-feeding and the number of negative breast-feeding beliefs held by respondents. Furthermore, women's normative beliefs and outcome beliefs were significantly correlated with breast-feeding intention in manners consistent with the model developed from the theory of reasoned action. After accounting for significant sociodemographic and lifestyle factors, the Processes of Change and outcome beliefs remained independently correlated with breast-feeding intention. These models are capable of predicting the intention to breast-feed and might offer an innovative approach for further breast-feeding research and intervention development.

Activation of CD4 T cells by somatic transgenesis induces generalized immunity of uncommitted T cells and immunologic memory.

Cellular immune responses were analyzed in vivo after a single intraspleen inoculation of DNA coding for a 12-residue Th cell determinant associated with a 12-residue B cell epitope, a process termed somatic transgene immunization. We show that CD4 T cells are readily activated and produce IL-2, IFN-gamma and IL-4, characteristics of an uncommitted phenotype. Linked recognition of the two epitopes coded in the same transgene promoted IgM-IgG1 switch and enhanced the total Ab response but had no effect on IgG2a Abs. Although originating in the spleen, T cell responsiveness was found to spread immediately and with similar characteristics to all lymph nodes in the body. A single inoculation was also effective in establishing long term immunologic memory as determined by limiting dilution analysis, with memory T cells displaying a cytokine profile different from that of primary effector T cells. These studies provide evidence that by initiating immunity directly in secondary lymphoid organs, an immune response is generated with characteristics that differ from those using vaccines of conventional DNA or protein in adjuvant administered in peripheral sites. Somatic transgene immunization can therefore be used to probe T cell responsiveness in vivo and represents a tool to further understanding of the nature of the adaptive immune response.

Relationships between physician advice and tobacco and alcohol use during pregnancy.

INTRODUCTION: We sought to examine relationships between physician advice and use of tobacco and alcohol during pregnancy among 683 women in the upper Midwest. METHODS: Data on risk of substance use during pregnancy were analyzed using logistic regression analysis. RESULTS: A higher proportion of women used tobacco (34%) than alcohol (25%) during their most recent pregnancy. Women who received advice from a physician to abstain from alcohol reported a lower risk of smoking and drinking during pregnancy than women who did not receive such advice. Risk of smoking and drinking during pregnancy was also common among women who reported early onset of alcohol use. CONCLUSIONS: Results suggest that physician advice regarding alcohol use during pregnancy is protective against maternal smoking and drinking during pregnancy.