Mapping Per- and Polyfluoroalkyl Substance Footprint from Cosmetics and Carpets across the Continental United States.

Per- and polyfluoroalkyl substances (PFAS) released from common consumer products, such as cosmetics and carpets, are nonpoint sources of environmental contamination. However, detailed information on PFAS mass and emission rates from these products is limited. Here, we propose a methodology to develop PFAS footprint from the manufacturing and supply chain data of cosmetics and carpets. Our analysis combines geospatial and statistical assessments to understand how the production and consumption of these products contribute to existing PFAS contamination hotspots in the Continental United States (CONUS). Statewide mass estimations revealed that North Carolina and New York contribute to the major PFAS mass released from cosmetics, while Georgia and California contribute to the major PFAS mass released from carpets. The average per capita PFAS footprint from carpets and cosmetics is about 103 mg/year. Upon disposal, over 60% of the mass eventually ends up in landfills. The accumulation of PFAS stocks in landfills, primarily from carpets and to some extent from cosmetics, highlights the critical need to cease the production and use of PFAS in consumer products. Coastal counties are particularly vulnerable due to higher population and therefore higher consumption of these PFAS-tainted consumer products. Additionally, counties with densely populated areas and with preexisting contamination sources would face increased vulnerability to PFAS contamination released from various consumer products.

Indicator metrics and temporal aggregations introduce ambiguities in water scarcity estimates.

Water scarcity is a global challenge affecting billions of people worldwide. This study systematically assesses differences in the estimation of the global population exposed to water scarcity based on 7 water scarcity indicators and 11 Environmental Flow Requirements (EFR) evaluated at various spatial and temporal resolutions. All indicators show an increase in water scarcity since 1901. However, considering monthly average water scarcity estimates spatially aggregated at the basin scale found 35% less population exposed than estimates based on a distributed grid over the landscape. Estimates temporally disaggregated to consider water scarcity for at least one month a year found 50% (tenfold) larger population exposed compared to average monthly (annual) estimates. The study illustrates that estimates of the impacts of water scarcity are an artifact of how water scarcity is defined and calculated. This suggests caution is needed when relying on a single method and emphasizes the importance of considering the diversity of factors that can influence estimates of impact when assessing water scarcity.

Prevalence and associated factors of teenage childbearing among Ethiopian women using semi-parametric and parametric proportional hazard and accelerated failure time models.

BACKGROUND: Teenage childbearing is a common issue for young people's sexual and reproductive health in the world, particularly in low-income countries, and affects teenagers between the ages of 13 and 19. According to several academics, adolescent pregnancy accounts for the majority of Ethiopia's population increase, and there has been little effort to address this threat. This study aimed to determine the prevalence and associated factors of the time to teenage childbearing in Ethiopia. METHOD: This paper compares the results of the semi-parametric proportional hazard (PH), parametric PH, and accelerated failure time (AFT) models to find the model that best fits the data. The Akaike Information Criterion (AIC) was used to evaluate the performance of models examined in this investigation. Time to teenage childbearing was the study's outcome variable, while the analysis considered various independent variables. We analyze data from the 2016 National Demographic Health Survey to assess the influence of different risk factors on teenage pregnancy among Ethiopian women. RESULTS: Out of the 10,274 teenagers (aged between 13 and 19) who participated in the 2016 survey, 6,430 (62.59%) were parents. The study findings revealed that these teenage parents were influenced by various time-related factors before becoming parents. The log-normal AFT model has the lowest AIC value and hence it is the best fit for this data. Results from this model indicated that significant factors influencing the time to teenage childbearing include the age of the household head, current age of the respondents, region, religion, educational attainment, wealth status, intention to use contraception, and recent sexual activity. CONCLUSION: This study reveals that 62.59% of surveyed teenagers aged 13 to 19 were parents. Various factors at both the individual and community levels: including the age of the household head, regional differences, religious affiliation, educational level, economic status, contraceptive intentions, and recent sexual activity, determine the time to teenage childbearing. Targeted interventions addressing these factors are essential for reducing teenage pregnancies and supporting adolescent parents effectively.

Exponentially fitted numerical method for solving singularly perturbed delay reaction-diffusion problem with nonlocal boundary condition.

OBJECTIVES: In this article, a singularly perturbed delay reaction-diffusion problem with nonlocal boundary conditions is considered. The exponential fitting factor is introduced to treat the solutions inside the boundary layer which occur due to perturbation parameter. The considered problem has interior layer at [Formula: see text] and strong boundary layers at [Formula: see text] and [Formula: see text]. We proposed an exponentially fitted finite difference method to solve the considered problem. The nonlocal boundary condition is treated using Composite Simpson's [Formula: see text] rule. RESULT: The stability and uniform convergence analysis of the proposed approach are established. The error estimation of the developed method is shown to be second-order uniform convergent. Two test examples were carried out to validate the applicability of the developed numerical method. The numerical results reflect the theoretical estimations.

Inputs for staple crop production in China drive burden shifting of water and carbon footprints transgressing part of provincial planetary boundaries.

Crop production is the biggest water user and key contributor to anthropogenic greenhouse gas emissions. Increasing crop yields to ensure adequate food supply under water and land scarcity is excessively dependents on intensive agricultural inputs (such as fertilizers, pesticides, agri-films, or energy), resulting in unintended environmental consequences. Supply chains bringing environmental-intensive inputs from their place of production to the croplands. However, most food-related environmental assessments ignore the environmental burden of agricultural input production, trade, and consumption. Here, we estimate spatially-detailed water (WF) and carbon footprints (CF) of wheat, maize, and rice production in China with extended system boundary from upstream raw material mining to the field. The agricultural inputs account for up to 24% and 89% of a crop's WF and CF, respectively, at the provincial level. The total local generated WF in Chinese northern provinces and CF in Shanxi and Inner Mongolia provinces for producing crops and agricultural inputs transgresses the corresponding downscaled blue water and carbon planetary boundaries. The study broadens the scope of traditional environmental impact assessments in agricultural production and sheds light on the significances to manage the linkages between the crop production and the agricultural inputs' upstream supply chains towards more efficient water use and less greenhouse gas emissions in food system.

Ex silico engineering of cystine-dense peptides yielding a potent bispecific T cell engager.

Cystine-dense peptides (CDPs) are a miniprotein class that can drug difficult targets with high affinity and low immunogenicity. Tools for their design, however, are not as developed as those for small-molecule and antibody drugs. CDPs have diverse taxonomic origins, but structural characterization is lacking. Here, we adapted Iterative Threading ASSEmbly Refinement (I-TASSER) and Rosetta protein modeling software for structural prediction of 4298 CDP scaffolds and performed in silico prescreening for CDP binders to targets of interest. Mammalian display screening of a library of docking-enriched, methionine and tyrosine scanned (DEMYS) CDPs against PD-L1 yielded binders from four distinct CDP scaffolds. One was affinity-matured, and cocrystallography yielded a high-affinity (KD = 202 pM) PD-L1-binding CDP that competes with PD-1 for PD-L1 binding. Its subsequent incorporation into a CD3-binding bispecific T cell engager produced a molecule with pM-range in vitro T cell killing potency and which substantially extends survival in two different xenograft tumor-bearing mouse models. Both in vitro and in vivo, the CDP-incorporating bispecific molecule outperformed a comparator antibody-based molecule. This CDP modeling and DEMYS technique can accelerate CDP therapeutic development.

Epidemiology of Epizootic Lymphangitis Among Carthorses in Ethiopia.

Epizootic lymphangitis caused by Histoplasma capsulatum variety farciminosum is a debilitating disease incurring considerable economic losses and affecting the welfare of carthorses. Understanding of its epidemiology is important for devising effective prevention and control measures. A cross-sectional study was conducted on 4,162 carthorses in 17 towns in Ethiopia between October 2018 and June 2019. Clinical and microscopic examinations, fungal culturing, and polymerase chain reaction were used to undertake this study. The overall prevalence of epizootic lymphangitis was 16.67% (95% CI: 15.55-17.84) in carthorses. Epizootic lymphangitis was detected in carthorses found in 16 of the 17 towns included in the study. The highest prevalence was recorded at Kombolcha Town (33.33; 95% CI: 27.54-39.52) whereas the lowest was recorded at Debre Birhan Town (0.00; 95% CI: 0.00-1.27). The results of univariable firth logistic regression analysis showed that the difference between the prevalence of Kombolcha and the prevalences of all the other towns except Holota and Shashemene were statistically significant. Statistically significantly lower prevalence was observed in other towns. Classification of the cases into different clinical forms showed that 87.18, 4.33, and 0.58% were cutaneous, ocular, and respiratory forms respectively, while the remaining 7.93% (55/694; 95% CI: 6.03-10.19) were classified as mixed form. In terms of the severity of the disease, 28.67, 60.52, and 0.81% were mild, moderate, and severe cases, respectively. The majority of the lesions (43.95%) were observed in the skin followed by forelimbs (14.55%) and neck region (14.27%). Higher mean annual temperature, lower annual rainfall, and higher humidity of the study towns were statistically significantly associated with an increased risk of epizootic lymphangitis. In conclusion this study revealed widespread occurrence of epizootic lymphangitis in carthorses yet a heterogeneous prevalence between towns. The veterinary and livestock authorities should take this into account while devising disease control.

Design of functionalised circular tandem repeat proteins with longer repeat topologies and enhanced subunit contact surfaces.

Circular tandem repeat proteins ('cTRPs') are de novo designed protein scaffolds (in this and prior studies, based on antiparallel two-helix bundles) that contain repeated protein sequences and structural motifs and form closed circular structures. They can display significant stability and solubility, a wide range of sizes, and are useful as protein display particles for biotechnology applications. However, cTRPs also demonstrate inefficient self-assembly from smaller subunits. In this study, we describe a new generation of cTRPs, with longer repeats and increased interaction surfaces, which enhanced the self-assembly of two significantly different sizes of homotrimeric constructs. Finally, we demonstrated functionalization of these constructs with (1) a hexameric array of peptide-binding SH2 domains, and (2) a trimeric array of anti-SARS CoV-2 VHH domains. The latter proved capable of sub-nanomolar binding affinities towards the viral receptor binding domain and potent viral neutralization function.

The scarcity-weighted water footprint provides unreliable water sustainability scoring.

To evaluate the environmental sustainability of blue water use or the blue water footprint (WF) of a product, organisation, geographical entity or a diet, two well-established indicators are generally applied: water efficiency and blue water stress. In recent years, the Life Cycle Assessment (LCA) community has developed, used and promoted the indicator scarcity-weighted WF, which aims to grasp both blue water use and blue water stress in one indicator. This indicator is now recommended in an ISO document on water footprinting and many scholars have used associated scarcity-weighted water use indicators. However, questions on its physical meaning and its ability to correctly evaluate water sustainability have emerged. Here, we analyse for global irrigated wheat production to what extend the scarcity-weighted WF addresses blue water stress and water efficiency. We observe inconsistent results, as a significant proportion of unsustainably produced irrigated wheat has better scarcity-weighted WF scores as compared to sustainably produced irrigated wheat. Using the scarcity-weighted WF or scarcity-weighted water use for policy-making including product labelling, punishes some farmers producing their wheat in a water-sustainable way and promotes some farmers producing wheat unsustainably. Applying the scarcity-weighted WF indicator thereby is contraproductive in reaching the Sustainable Development Goal (SDG) target 6.4 on reducing water stress. In line with the specifications of this SDG target, to evaluate the sustainability of blue water use or the blue WF, the two indicators water stress and water efficiency should be used separately, in a complementary way.

Treenuts and groundnuts in the EAT-Lancet reference diet: Concerns regarding sustainable water use.

The EAT-Lancet universal healthy reference diet recommends an increase in the consumption of healthy foods, among which treenuts and groundnuts. Both are, however, water-intensive products, with a large water footprint (WF) per unit of mass and protein and already today contribute to blue water stress in different parts of the world. The envisaged massive required increase in nut production to feed a global population with this reference diet, needs to occur in a water-sustainable way. In this paper, we identify and quantify where current nut production contributes to local blue water stress and discuss options for water-sustainable nut production. We show that 74% of irrigated nuts are produced under blue water stress (of which 63% under severe water stress), throughout many regions of the world, most notably in India, China, Pakistan, the Middle East, the Mediterranean region and the USA. We critically evaluate which nut types to promote given substantial differences in WFs. We propose sustainable intensification of nut production employing nut-specific WF benchmarks. We also recommend integrated water resources management including maximum sustainable levels of water consumption by setting of WF caps.

A potent peptide-steroid conjugate accumulates in cartilage and reverses arthritis without evidence of systemic corticosteroid exposure.

On-target, off-tissue toxicity limits the systemic use of drugs that would otherwise reduce symptoms or reverse the damage of arthritic diseases, leaving millions of patients in pain and with limited physical mobility. We identified cystine-dense peptides (CDPs) that rapidly accumulate in cartilage of the knees, ankles, hips, shoulders, and intervertebral discs after systemic administration. These CDPs could be used to concentrate arthritis drugs in joints. A cartilage-accumulating peptide, CDP-11R, reached peak concentration in cartilage within 30 min after administration and remained detectable for more than 4 days. Structural analysis of the peptides by crystallography revealed that the distribution of positive charge may be a distinguishing feature of joint-accumulating CDPs. In addition, quantitative whole-body autoradiography showed that the disulfide-bonded tertiary structure is critical for cartilage accumulation and retention. CDP-11R distributed to joints while carrying a fluorophore imaging agent or one of two different steroid payloads, dexamethasone (dex) and triamcinolone acetonide (TAA). Of the two payloads, the dex conjugate did not advance because the free drug released into circulation was sufficient to cause on-target toxicity. In contrast, the CDP-11R-TAA conjugate alleviated joint inflammation in the rat collagen-induced model of rheumatoid arthritis while avoiding toxicities that occurred with nontargeted steroid treatment at the same molar dose. This conjugate shows promise for clinical development and establishes proof of concept for multijoint targeting of disease-modifying therapeutic payloads.

Blue water footprint linked to national consumption and international trade is unsustainable.

Increasing pressure on the world's freshwater resources raises serious concerns about global food security and the sustainability of water use in agriculture. Here we quantify and map at a 5-arcmin spatial resolution the blue water footprint of each country's national consumption and where they infringe sustainable environmental flows as defined by the presumptive environmental flow standard or the 80% rule, in which runoff depletion by more than 20% will pose risk to ecosystems. We find that 52% of the blue water footprint of global consumption and 43% of international blue virtual water flows come from places where the sustainable environmental flow is violated. About 22% of the environmental flow infringement of the blue water footprint of global consumption lies outside the specific countries of consumption, indicating that a number of them have externalized their impacts. By establishing a link between the consumption of a product in one place and water scarcity in places far from the place of consumption, our assessment may aid a dialogue on how to assign and share responsibilities concerning water use.

Water productivity in meat and milk production in the US from 1960 to 2016.

Global demand for livestock products is rising, resulting in a growing demand for feed and potentially burdening freshwater resources to produce this feed. To offset this increased pressure on water resources, the environmental performance of livestock sector should continue to improve. Over the last few decades, product output per animal and feedstuff yields in the US have improved, but before now it was unclear to what extent these improvements influenced the water productivity (WP) of the livestock products. In this research, we estimate changes in WP of animal products from 1960 to 2016. We consider feed conversion ratios (dry matter intake per head divided by product output per head), feed composition per animal category, and estimated the water footprint of livestock production following the Water Footprint Network's Water Footprint Assessment methodology. The current WP of all livestock products appears to be much better than in 1960. The observed improvements in WPs are due to a number of factors, including increases in livestock productivity, feed conversion ratios and feed crop yields, the latter one reducing the water footprint of feed inputs. Monogastric animals (poultry and swine) have a high feed-use efficiency compared to ruminants (cattle), but ruminants consume relatively large portion of feed that is non-edible for humans. Per unit of energy content, milk has the largest WP followed by chicken and pork. Per gram of protein, poultry products (chicken meat, egg and turkey meat) have the largest WP, followed by cattle milk and pork. Beef has the smallest WP. These data provide important information that may aid the development of strategies to improve WP of the livestock sector.

Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes.

Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.

Limits to the world's green water resources for food, feed, fiber, timber, and bioenergy.

Green water--rainfall over land that eventually flows back to the atmosphere as evapotranspiration--is the main source of water to produce food, feed, fiber, timber, and bioenergy. To understand how freshwater scarcity constrains production of these goods, we need to consider limits to the green water footprint (WFg), the green water flow allocated to human society. However, research traditionally focuses on scarcity of blue water--groundwater and surface water. Here we expand the debate on water scarcity by considering green water scarcity (WSg). At 5 × 5 arc-minute spatial resolution, we quantify WFg and the maximum sustainable level to this footprint (WFg,m), while accounting for green water requirements to support biodiversity. We then estimate WSg per country as the ratio of the national aggregate WFg to the national aggregate WFg,m We find that globally WFg amounts to 56% of WFg,m, and overshoots it in several places, for example in countries in Europe, Central America, the Middle East, and South Asia. The sustainably available green water flows in these countries are mostly or fully allocated to human activities (predominately agriculture and forestry), occasionally at the cost of green water flows earmarked for nature. By ignoring limits to the growing human WFg, we risk further loss of ecosystem values that depend on the remaining untouched green water flows. We emphasize that green water is a critical and limited resource that should explicitly be part of any assessment of water scarcity, food security, or bioenergy potential.

Water, Energy, and Carbon Footprints of Bioethanol from the U.S. and Brazil.

Driven by biofuel policies, which aim to reduce greenhouse gas (GHG) emissions and increase domestic energy supply, global production and consumption of bioethanol have doubled between 2007 and 2016, with rapid growth in corn-based bioethanol in the U.S. and sugar cane-based bioethanol in Brazil. Advances in crop yields, energy use efficiency in fertilizer production, biomass-to-ethanol conversion rates, and energy efficiency in ethanol production have improved the energy balance and GHG emission reduction potential of bioethanol. In the current study, the water, energy, and carbon footprints of bioethanol from corn in the U.S. and sugar cane in Brazil were assessed. The results show that U.S. corn bioethanol has a smaller water footprint (541 L water/L bioethanol) than Brazilian sugar cane bioethanol (1115 L water/L bioethanol). Brazilian sugar cane bioethanol has, however, a better energy balance (17.7 MJ/L bioethanol) and smaller carbon footprint (38.5 g CO2e/MJ) than U.S. bioethanol, which has an energy balance of 11.2 MJ/L bioethanol and carbon footprint of 44.9 g CO2e/MJ. The results show regional differences in the three footprints and highlight the need to take these differences into consideration to understand the implications of biofuel production for local water resources, net energy production, and climate change mitigation.

Screening, large-scale production and structure-based classification of cystine-dense peptides.

Peptides folded through interwoven disulfides display extreme biochemical properties and unique medicinal potential. However, their exploitation has been hampered by the limited amounts isolatable from natural sources and the expense of chemical synthesis. We developed reliable biological methods for high-throughput expression, screening and large-scale production of these peptides: 46 were successfully produced in multimilligram quantities, and >600 more were deemed expressible through stringent screening criteria. Many showed extreme resistance to temperature, proteolysis and/or reduction, and all displayed inhibitory activity against at least 1 of 20 ion channels tested, thus confirming their biological functionality. Crystal structures of 12 confirmed proper cystine topology and the utility of crystallography to study these molecules but also highlighted the need for rational classification. Previous categorization attempts have focused on limited subsets featuring distinct motifs. Here we present a global definition, classification and analysis of >700 structures of cystine-dense peptides, providing a unifying framework for these molecules.

Control of Tumor Initiation by NKG2D Naturally Expressed on Ovarian Cancer Cells.

Cancer cells may co-opt the NKG2D lymphocyte receptor to complement the presence of its ligands for autonomous stimulation of oncogenic signaling. Previous studies raise the possibility that cancer cell NKG2D may induce high malignancy traits, but its full oncogenic impact is unknown. Using epithelial ovarian cancer as model setting, we show here that ex vivo NKG2D+ cancer cells have stem-like capacities, and provide formal in vivo evidence linking NKG2D stimulation with the development and maintenance of these functional states. NKG2D+ ovarian cancer cell populations harbor substantially greater capacities for self-renewing in vitro sphere formation and in vivo tumor initiation in immunodeficient (NOD scid gamma) mice than NKG2D- controls. Sphere formation and tumor initiation are impaired by NKG2D silencing or ligand blockade using antibodies or a newly designed pan ligand-masking NKG2D multimer. In further support of pathophysiological significance, a prospective study of 47 high-grade serous ovarian cancer cases revealed that the odds of disease recurrence were significantly greater and median progression-free survival rates higher among patients with above and below median NKG2D+ cancer cell frequencies, respectively. Collectively, our results define cancer cell NKG2D as an important regulator of tumor initiation in ovarian cancer and presumably other malignancies and thus challenge current efforts in immunotherapy aimed at enhancing NKG2D function.