Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

Search for lepton flavor violating decays of a heavy neutral particle in p(p)over-bar collisions at root s=1.8 TeV

We report on a search for a high mass, narrow width particle that decays directly to emu, etau, or mutau. We use approximately 110 pb(-1) of data collected with the Collider Detector at Fermilab from 1992 to 1995. No evidence of lepton flavor violating decays is found. Limits are set on the production and decay of sneutrinos with R-parity violating interactions

Discovery of naked charm particles and lifetime differences among charm species using nuclear emulsion techniques innovated in Japan

This is a historical review of the discovery of naked charm particles and lifetime differences among charm species. These discoveries in the field of cosmic-ray physics were made by the innovation of nuclear emulsion techniques in Japan. A pair of naked charm particles was discovered in 1971 in a cosmic-ray interaction, three years prior to the discovery of the hidden charm particle, J/Ψ, in western countries. Lifetime differences between charged and neutral charm particles were pointed out in 1975, which were later re-confirmed by the collaborative Experiment E531 at Fermilab. Japanese physicists led by K.Niu made essential contributions to it with improved emulsion techniques, complemented by electronic detectors. This review also discusses the discovery of artificially produced naked charm particles by us in an accelerator experiment at Fermilab in 1975 and of multiple-pair productions of charm particles in a single interaction in 1987 by the collaborative Experiment WA75 at CERN

Dietary patterns associated with fall-related fracture in elderly Japanese: a population based prospective study

<p>Abstract</p> <p>Background</p> <p>Diet is considered an important factor for bone health, but is composed of a wide variety of foods containing complex combinations of nutrients. Therefore we investigated the relationship between dietary patterns and fall-related fractures in the elderly.</p> <p>Methods</p> <p>We designed a population-based prospective survey of 1178 elderly people in Japan in 2002. Dietary intake was assessed with a 75-item food frequency questionnaire (FFQ), from which dietary patterns were created by factor analysis from 27 food groups. The frequency of fall-related fracture was investigated based on insurance claim records from 2002 until 2006. The relationship between the incidence of fall-related fracture and modifiable factors, including dietary patterns, were examined. The Cox proportional hazards regression model was used to examine the relationships between dietary patterns and incidence of fall-related fracture with adjustment for age, gender, Body Mass Index (BMI) and energy intake.</p> <p>Results</p> <p>Among 877 participants who agreed to a 4 year follow-up, 28 suffered from a fall-related fracture. Three dietary patterns were identified: mainly vegetable, mainly meat and mainly traditional Japanese. The moderately confirmed (see statistical methods) groups with a Meat pattern showed a reduced risk of fall-related fracture (Hazard ratio = 0.36, 95% CI = 0.13 - 0.94) after adjustment for age, gender, BMI and energy intake. The Vegetable pattern showed a significant risk increase (Hazard ratio = 2.67, 95% CI = 1.03 - 6.90) after adjustment for age, gender and BMI. The Traditional Japanese pattern had no relationship to the risk of fall-related fracture.</p> <p>Conclusions</p> <p>The results of this study have the potential to reduce fall-related fracture risk in elderly Japanese. The results should be interpreted in light of the overall low meat intake of the Japanese population.</p

Core Planar Cell Polarity Genes VANGL1 and VANGL2 in Predisposition to Congenital Vertebral Malformations

Congenital scoliosis (CS) is the most common congenital spinal disorder caused by congenital vertebral malformations (CVMs), influenced by genetic and environmental factors and exhibiting diverse clinical presentations. Here, we identified the critical roles of Vangl1 and Vangl2, two core components in the Wnt/planar cell polarity (Wnt/PCP) signaling pathway, in vertebral development and in predisposition to CVMs in CS patients. We found that in Vangl mutant mouse models, the CVMs present in a Vangl gene dose- and gestational hypoxia-dependent manner. Our studies reveal a complex etiology of CS and its association with Wnt/PCP signaling

Chronic Hepatitis C

The goal of antiviral therapy for patients with chronic hepatitis C virus (HCV) infection is to attain a sustained virologic response (SVR), which is defined as undetectable serum HCV-RNA levels at 6 months after the cessation of treatment. Major improvements in antiviral therapy for chronic hepatitis C have occurred in the past decade. The addition of ribavirin to interferon-alfa therapy and the introduction of pegylated interferon (PEG-IFN) have substantially improved SVR rates in patients with chronic hepatitis C. The optimization of HCV therapy with PEG-IFN and ribavirin continues to evolve. Studies are ongoing that use viral kinetics to tailor therapy to an individual's antiviral response and determine the ideal length of treatment to maximize the chance of SVR. Improved SVR can be achieved with new specific inhibitors that target the HCV NS3/4A protease and the NS5B polymerase. Several long-term follow-up studies have shown that SVR, when achieved, is associated with a very low risk of virologic relapse. Furthermore, antiviral therapy can reduce the morbidity and mortality rates associated with chronic hepatitis C by reducing fibrosis progression, the incidence of cirrhosis, and hepatocellular carcinoma

Life cycle assessment of European anchovy (Engraulis encrasicolus) landed by purse seine vessels in northern Spain

Purpose: The main purpose of this article is to assess the environmental impacts associated with the fishing operations related to European anchovy fishing in Cantabria (northern Spain) under a life cycle approach. Methods: The life cycle assessment (LCA) methodology was applied for this case study including construction, maintenance, use, and end of life of the vessels. The functional unit used was 1 kg of landed round anchovy at port. Inventory data were collected for the main inputs and outputs of 32 vessels, representing a majority of vessels in the fleet. Results and discussion: Results indicated, in a similar line to what is reported in the literature, that the production, transportation, and use of diesel were the main environmental hot spots in conventional impact categories. Moreover, in this case, the production and transportation of seine nets was also relevant. Impacts linked to greenhouse gas (GHG) emissions suggest that emissions were in the upper range for fishing species captured with seine nets and the value of global warming potential (GWP) was 1.44 kg CO2 eq per functional unit. The ecotoxicity impacts were mainly due to the emissions of antifouling substances to the ocean. Regarding fishery-specific categories, many were discarded given the lack of detailed stock assessments for this fishery. Hence, only the biotic resource use category was computed, demonstrating that the ecosystems' effort to sustain the fishery is relatively low. Conclusions: The use of the LCA methodology allowed identifying the main environmental hot spots of the purse seining fleet targeting European anchovy in Cantabria. Individualized results per port or per vessel suggested that there are significant differences in GHG emissions between groups. In addition, fuel use is high when compared to similar fisheries. Therefore, research needs to be undertaken to identify why fuel use is so high, particularly if it is related to biomass and fisheries management or if skipper decisions could play a role.The authors thank the Ministry of Economy and Competitiveness of the Spanish Government for their financial support via the project GeSAC-Conserva: Sustainable Management of the Cantabrian Anchovies (CTM2013-43539-R) and to Pedro Villanueva-Rey for valuable scientific exchange. Jara Laso thanks the Ministry of Economy and Competitiveness of Spanish Government for their financial support via the research fellowship BES-2014-069368 and to the Ministry of Rural Environment, Fisheries and Food of Cantabria for the data support. Dr. Ian Vázquez-Rowe thanks the Peruvian LCA Network for operational support. Reviewers are also thanked for the valuable and detailed suggestions. The work of Dr. Rosa M. Crujeiras has been funded by MTM2016-76969P (AEI/FEDER, UE)

Birth outcomes in relation to neighborhood food access and individual food insecurity during pregnancy in the Environmental Influences on Child Health Outcomes (ECHO)-wide cohort study

BackgroundLimited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied.ObjectivesWe examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes.MethodsWe used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is &gt;0.5 miles for urban or &gt;10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and &gt;0.5 miles from the nearest supermarket) neighborhoods and&nbsp;individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics.ResultsAmong 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [β -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed.ConclusionsResidence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes

Belt and Road Initiative in Central Asia: Anticipating socioecological challenges from large‐scale infrastructure in a global biodiversity hotspot

Until recently, China's Belt and Road Initiative (BRI) has overlooked many of the social and environmental dimensions of its projects and actions in favor of more immediate economic and sociopolitical considerations. The main focus of investments under BRI has largely been to improve transport, telecommunication, and energy infrastructures. However, in Central Asia, biodiversity is not only foundational for the livelihoods and socioeconomic wellbeing of communities, it also shapes people's culture and identities. Furthermore, ecosystem services derived from functioning landscapes bring enormous benefit for millions of people downstream through integrated and transboundary water systems. Already under pressure from climate-induced melting of glaciers, the fate of ecologically important areas is considered in light of the potential harm arising from large-scale linear infrastructure projects and related investments under China-led BRI. Following review of some of the anticipated impacts of BRI on mountain environments and societies in the region, we highlight several emerging opportunities and then offer recommendations for development programs—aiming fundamentally to enhance the sustainability of BRI investments. Leveraging new opportunities to strengthen partner countries’ priority Sustainable Development Goals and enhancing their agency in the selection of collaborations and the standards to use in environmental impact and risk assessments are recommended