OBJECTIVES/GOALS:

• Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized structurally and mechanistically. The gold particles should enhance radiation activity by closer proximity to the photosensitizer and by increasing particle accumulation in the tumor.

METHODS/STUDY POPULATION:

• Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol, then covalently conjugated to chlorin e6, a known FDA-approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species was measured after X-irradiation. Enhanced cell killing was evaluated clonogenically in addition to assessment of in vivo efficacy and tumor pathology.

RESULTS/ANTICIPATED RESULTS:

• Conjugation of the particle to the photosensitizer was achieved, and the molecule was detected by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates increased cell killing during radiation treatment, whereas neither the particle alone nor the photosensitizer significantly affected clonogenic survival at the same concentrations. Breast tumors grown in immunocompetent mice showed increased necrotic tissue after a single 20 gy treatment in the presence of the conjugate.

DISCUSSION/SIGNIFICANCE OF IMPACT: Radiation therapy is widely used clinically, but dosage is limited largely to prevent injury to adjacent normal tissue. By increasing the local effect of radiation therapy, our gold conjugate has the potential to augment the effective radiation dose in the tumor, thereby reducing damage to healthy tissue and providing a more effective therapy.

This paper examines the work and lives of black female activist intellectuals in the years before the formation of the National Association of Colored Women's Clubs (NACWC) in 1896. Looking deeper at arguments originally made by Maria Stewart concerning the denial of black women's ambitions and limiting potential in their working lives, the analysis employs the work of the Italian Marxist Antonio Gramsci, in particular his notion of the intellectual, to help reflect on the centrality of these black women in the development of an early counterhegemonic movement.

Methods to stimulate appetite in the sick or elderly remains a challenge with few safe therapeutic options. Ghrelin is an orexigenic hormone, increasing appetite and subsequent food intake. It has received considerable attention as a therapeutic target to stimulate food intake in patients with anorexia. The identification of food-grade bioactives with proven orexigenic effects would mark significant progress in the treatment of disease-related malnutrition. This study therefore investigated the effects of two milk-derived ghrelinergic peptides on appetite and energy intake in healthy humans.

A single-blind, placebo-controlled, 3-arm (placebo, casein bioactive MF1145 and whey bioactive UL-2-141) cross-over trial was conducted in healthy male volunteers. Participants received 26 mg/kg of both the bioactives and placebo. The main outcome measures were energy & protein intake from a set breakfast and ad libitum lunch and subjective appetite sensations as assessed by visual analogue scale (VAS). Basal and postprandial levels of active ghrelin (AG) were measured. Dietary intakes were analysed using Nutritics software. Statistical analyses were performed in R.

Overall, 22 male participants (mean age 27 years) were included, average BMI was 24.6 kg/m2, (19.8 to 30.2 kg/m2). Mean energy and protein intakes at lunch when treated with placebo were 1343 kcal (95% CI: 1215–1471 kcal) and 74 g (95% CI: 66–81 g), respectively. Energy and protein intakes were not significantly different from placebo for either treatment (p = 0.918, p = 0.319 for UL-2-141 and p = 0.889, p = 0.959 for MF1145, respectively). Similarly, appetite, hunger and satiety responses on VAS were not significantly different from placebo for either treatment. AG peak post-lunch on placebo was 653 pg/ml (95% CI: 511–794 pg/ml). Treatment with UL-2-141 resulted in 139 pg/ml reduction in post-prandial AG compared to placebo and treatment with MF1145 resulted in 114 pg/ml reduction compared to placebo. This pattern was significant for both treatments (p = 0.021 and p = 0.045, respectively) however when controlling for fasting-AG, the pattern was no longer significant (p = 0.590 and p = 0.877 respectively). Pre-prandial AG peaks were not significantly different across treatments.

While these peptides have previously demonstrated ghrelinergic effects in rats, no effect on appetite or food intake in humans was identified by this study. This may be attributable to the small sample size or low dose. However, since healthy adults are often not in tune with their own physiological hunger, they may not respond strongly to simple physiological modulators and repeating the study in subjects with established anorexia may be prudent.

What is the role of Northeastern agricultural products in the US food system? This paper presents a typology that categorizes where agricultural production and distribution of a specific geographic area, in this case a multi-state region, fits within the US food system. The place of each food is defined based on its production volume, scope of distribution, market timing and agro-ecological niche. Six distinct roles that a region might play in supplying food are identified: (a) the region is a national production center, (b) the region is a seasonally important supplier, (c) regional production and distribution is the primary scale for supplying a food, (d) the product occupies an agro-ecological niche, (e) a product is a co-product of another industry in the region, and (f) the product is marketed explicitly for its geographic provenance as a local or regional product. Illustrative examples of each role are provided from the research of the Enhancing Food Security in the Northeast (EFSNE) regional food systems project. The examples draw from a variety of methodological approaches including regional self-reliance analysis, product case studies, supply chain models, and examination of spatial and temporal patterns in crop and livestock production and marketing. While presented in the context of the Northeast, the typology would likely be valuable for characterizing other regions of the country. We need such a typology to better understand and communicate the value of geographically dispersed agricultural production to creating a resilient food system, thereby improving our decisions of how to respond to future agricultural challenges

Evidence from randomised controlled trials supports beneficial effects of total dairy products on body weight, fat and lean mass, but evidence on associations of dairy types with distributions of body fat and lean mass is limited. We aimed to investigate associations of total and different types of dairy products with markers of adiposity, and body fat and lean mass distribution. We evaluated cross-sectional data from 12 065 adults aged 30–65 years recruited to the Fenland Study between 2005 and 2015 in Cambridgeshire, UK. Diet was assessed with an FFQ. We estimated regression coefficients (or percentage differences) and their 95 % CI using multiple linear regression models. The medians of milk, yogurt and cheese consumption were 293 (interquartile range (IQR) 146–439), 35·3 (IQR 8·8–71·8) and 14·6 (IQR 4·8–26·9) g/d, respectively. Low-fat dairy consumption was inversely associated with visceral:subcutaneous fat ratio estimated with dual-energy X-ray absorptiometry (–2·58 % (95 % CI –3·91, –1·23 %) per serving/d). Habitual consumption per serving/d (200 g) of milk was associated with 0·33 (95 % CI 0·19, 0·46) kg higher lean mass. Other associations were not significant after false discovery correction. Our findings suggest that the influence of milk consumption on lean mass and of low-fat dairy consumption on fat mass distribution may be potential pathways for the link between dairy consumption and metabolic risk. Our cross-sectional findings warrant further research in prospective and experimental studies in diverse populations.

One major challenge facing policy-makers is to design education and workplace training programs that are appropriately challenging. We review previous research that suggests that difficult training is better than easy training. However, surveys we conducted of students and of expert sport coaches showed that many prescribed easy rather than difficult training for those they coached. We analyzed the performance of National Collegiate Athletic Association (NCAA) basketball teams in postseason tournaments to see whether the existing research, largely on individuals in short-term situations, would generalize to teams in the long run. Indeed, playing difficult nonconference (training) games modestly improved performance for NCAA teams in the postseason. Difficult training particularly benefitted teams that lost many nonconference games, and the effect of difficulty was positive within the range of difficulty NCAA teams actually encounter, making it clear that difficult training is superior. We suggest that our results can be generalized beyond sports, although with careful consideration of differences between NCAA basketball teams and other teams that may limit generalizability. These results suggest that policy-makers might consider amplifying the difficulty of team training exercises under certain conditions.

With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.

Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.

Measurements in the infrared wavelength domain allow direct assessment of the physical state and energy balance of cool matter in space, enabling the detailed study of the processes that govern the formation and evolution of stars and planetary systems in galaxies over cosmic time. Previous infrared missions revealed a great deal about the obscured Universe, but were hampered by limited sensitivity.

SPICA takes the next step in infrared observational capability by combining a large 2.5-meter diameter telescope, cooled to below 8 K, with instruments employing ultra-sensitive detectors. A combination of passive cooling and mechanical coolers will be used to cool both the telescope and the instruments. With mechanical coolers the mission lifetime is not limited by the supply of cryogen. With the combination of low telescope background and instruments with state-of-the-art detectors SPICA provides a huge advance on the capabilities of previous missions.

SPICA instruments offer spectral resolving power ranging from R ~50 through 11 000 in the 17–230 μm domain and R ~28.000 spectroscopy between 12 and 18 μm. SPICA will provide efficient 30–37 μm broad band mapping, and small field spectroscopic and polarimetric imaging at 100, 200 and 350 μm. SPICA will provide infrared spectroscopy with an unprecedented sensitivity of ~5 × 10−20 W m−2 (5σ/1 h)—over two orders of magnitude improvement over what earlier missions. This exceptional performance leap, will open entirely new domains in infrared astronomy; galaxy evolution and metal production over cosmic time, dust formation and evolution from very early epochs onwards, the formation history of planetary systems.

Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.

High cost of healthy foods could be a barrier to healthy eating. We aimed to examine the association between dietary cost and adherence to the Mediterranean diet in a non-Mediterranean country. We evaluated cross-sectional data from 12 417 adults in the UK Fenland Study. Responses to 130-item FFQ were used to calculate a Mediterranean diet score (MDS). Dietary cost was estimated by matching food consumption data with retail prices of five major supermarkets. Using multivariable-adjusted linear regression, we examined the association of MDS and individual foods with dietary cost in absolute and relative scales. Subsequently, we assessed how much the association was explained by education, income, marital status and occupation, by conducting mediation analysis and testing interaction by these variables. High compared with low MDS (top to bottom third) was associated with marginally higher cost by 5·4 % (95 % CI 4·4, 6·4) or £0·20/d (95 % CI 0·16, 0·25). Participants with high adherence had higher cost associated with the healthier components (e.g. vegetables, fruits and fish), and lower cost associated with the unhealthy components (e.g. red meat, processed meat and sweets) (P for trend<0·001 each). In total, 20·7 % (95 % CI 14·3, 27·0) of the MDS-cost association was explained by the selected socio-economic factors, and the MDS-cost association was of greater magnitude in lower socio-economic groups (P interaction<0·005). Overall, greater adherence to the Mediterranean diet was associated with marginally higher dietary cost, partly modified and explained by socio-economic status, but the potential economic barriers of high adherence might be offset by cost saving from reducing unhealthy food consumption.