There's no place like real-space:elucidating size-dependent atomic structure of nanomaterials using pair distribution function analysis

The development of new functional materials builds on an understanding of the intricate relationship between material structure and properties, and structural characterization is a crucial part of materials chemistry. However, elucidating the atomic structure of nanomaterials remains a challenge using conventional diffraction techniques due to the lack of long-range atomic order. Over the past decade, Pair Distribution Function (PDF) analysis of X-ray or neutron total scattering data has become a mature and well-established method capable of giving insight into the atomic structure in nanomaterials. Here, we review the use of PDF analysis and modelling in characterization of a range of different nanomaterials that exhibit unique atomic structure compared to the corresponding bulk materials. A brief introduction to PDF analysis and modelling is given, followed by examples of how essential structural information can be extracted from PDFs using both model-free and advanced modelling methods. We put an emphasis on how the intuitive nature of the PDF can be used for understanding important structural motifs, and on the diversity of applications of PDF analysis to nanostructure problems

Intake of Supplemental Deer Pellets Containing Ground Blueberry Juniper by Wild Pigs

Supplemental feeding of cervid species such as white-tailed deer (Odocoileus virginianus; deer) is now a common management practice in the United States. Supplemental feeding can be costly and more expensive when supplements are consumed by non-target species such as wild pigs (Sus scrofa; pigs). From May 13 to June 17, 2015, we evaluated the effects of using ground blueberry juniper (Juniperus ashei) or cottonseed (Gossypium spp.) hulls as a roughage ingredient in a supplemental deer pellet to deter pig consumption at the Texas A&M AgriLife Research Center in San Angelo, Texas, USA. We analyzed dry matter intake, growth performance, in vitro digestibility and fermentation, and blood serum chemistry of pigs using a 2 × 2 factorial study design that included 3 feeding periods. Pigs were assigned to 1 of 4 supplement diets (n = 5 pigs/supplement) or to a commercially available swine diet (BASAL; n = 4 pigs). Animals assigned to supplement diets were also offered BASAL based on percentage of body weight (BW) during each period. Supplement diets differed by roughage source and percentage of roughage: cottonseed hulls 20%, cottonseed hulls 40%, blueberry juniper 20%, or blueberry juniper 40%. During each period, the amount of supplement and BASAL diet offered to animals assigned to a supplement was fed as a percentage of BW; period 1 (day 0 to 17) = 5% supplement diet and 5% BASAL diet, period 2 (day 18 to 26) = 5% supplement diet and 2% BASAL diet, period 3 (day 27 to 34) = 5% supplement diet and 5% BASAL diet. Animals assigned to only BASAL were offered the same amount of feed as a percent of BW as supplement animals during each period. We observed a roughage × period interaction (P = 0.03) for supplement dry matter intake g/day and a roughage × period interaction (P \u3c 0.09) for total dry matter intake as a percentage of BW. No differences were observed within period. No other variables had percent roughage x period differences. Ground blueberry juniper was indigestible by pigs; the in vitro digestibility of dry matter and gross energy was \u3c 1%. Greater blood serum alanine aminotransferase (P= 0.07) in pigs consuming experimental supplement diets suggested the possibility of liver damage. Our findings suggest that there does not appear to be a benefit of using ground juniper as a roughage source to reduce consumption of supplemental deer feed by pigs

Prenatal development is linked to bronchial reactivity: epidemiological and animal model evidence

Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11-19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans

Mental Stress Provokes Ischemia in Coronary Artery Disease Subjects Without Exercise- or Adenosine-Induced Ischemia

ObjectivesThe purpose of this study was to investigate the possibility that some patients with coronary artery disease (CAD) but negative exercise or chemical stress test results might have mental stress-induced ischemia. The study population consisted solely of those with negative test results.BackgroundMental stress-induced ischemia has been reported in 20% to 70% of CAD subjects with exercise-induced ischemia. Because mechanisms of exercise and mental stress-induced ischemia may differ, we studied whether mental stress would produce ischemia in a proportion of subjects with CAD who have no inducible ischemia with exercise or pharmacologic tests.MethodsTwenty-one subjects (14 men, 7 women) with a mean age of 67 years and with a documented history of CAD were studied. All subjects had a recent negative nuclear stress test result (exercise or chemical). Subjects completed a speaking task involving role playing a difficult interpersonal situation. A total of 30 mCi 99mTc-sestamibi was injected at one minute into the speech, and imaging was started 40 min later. A resting image obtained within one week was compared with the stress image. Images were analyzed for number and severity of perfusion defects. The summed difference score based on the difference between summed stress and rest scores was calculated. Severity was assessed using a semiquantitative scoring method from zero to four.ResultsSix of 21 (29%) subjects demonstrated reversible ischemia (summed difference score ≥3) with mental stress. No subject had chest pain or electrocardiographic changes during the stressor. Mean systolic and diastolic blood pressure and heart rate all increased between resting and times of peak stress.ConclusionsMental stress may produce ischemia in some subjects with CAD and negative exercise or chemical nuclear stress test results

Results of a feasibility randomised controlled trial (RCT) for WATCH IT: a programme for obese children and adolescents

Background: In the evaluation of childhood obesity interventions, few researchers undertake a rigorous feasibility stage in which the design and procedures of the evaluation process are examined. Consequently, phase III studies often demonstrate methodological weaknesses. Purpose: Our aim was to conduct a feasibility trial of the evaluation of WATCH IT, a community obesity intervention for children and adolescents. We sought to determine an achievable recruitment rate; acceptability of randomisation, assessment procedures, and dropout rate; optimal outcome measures for the definitive trial; and a robust sample size calculation. Method: Our goal was to recruit 70 participants over 6 months, randomise them to intervention or control group, and retain participation for 12 months. Assessments were taken prior to randomisation and after 6 and 12 months. Procedures mirrored those intended for a full-scale trial, but multiple measures of similar outcomes were included as a means to determine those most appropriate for future research. Acceptability of the research and impact of the research on the programme were ascertained through interviewing participants and staff. Results: We recruited 70 participants and found that randomisation and data collection procedures were acceptable. Self-referral (via media promotion) was more effective than professional referral. Blinding of assessors was sustained to a reasonable degree, and optimal outcome measures for a full-scale trial were identified. Estimated sample size was significantly greater than sample sized reported in published trials. There was some negative impact on the existing programme as a result of the research, a lesson for designers of future trials. Limitations: We successfully recruited socially disadvantaged families, but the majority of families were of White British nationality. The composition of the participants was an added valuable lesson, suggesting that recruitment strategies to obtain a more heterogeneous ethnic sample warrant consideration in future research. Conclusions: This study provided us with confidence that we can run a phase III multi-centre trial to test the effectiveness of WATCH IT. Importantly, it was invaluable in informing the design not only of that trial but also of future evaluations of childhood obesity treatment interventions

Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Taskforce

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63263/1/thy.2006.16.109.pd

The Waldschmidt constant for squarefree monomial ideals

Given a squarefree monomial ideal $I \subseteq R =k[x_1,\ldots,x_n]$, we show that $\widehat\alpha(I)$, the Waldschmidt constant of $I$, can be expressed as the optimal solution to a linear program constructed from the primary decomposition of $I$. By applying results from fractional graph theory, we can then express $\widehat\alpha(I)$ in terms of the fractional chromatic number of a hypergraph also constructed from the primary decomposition of $I$. Moreover, expressing $\widehat\alpha(I)$ as the solution to a linear program enables us to prove a Chudnovsky-like lower bound on $\widehat\alpha(I)$, thus verifying a conjecture of Cooper-Embree-H\`a-Hoefel for monomial ideals in the squarefree case. As an application, we compute the Waldschmidt constant and the resurgence for some families of squarefree monomial ideals. For example, we determine both constants for unions of general linear subspaces of $\mathbb{P}^n$ with few components compared to $n$, and we find the Waldschmidt constant for the Stanley-Reisner ideal of a uniform matroid.Comment: 26 pages. This project was started at the Mathematisches Forschungsinstitut Oberwolfach (MFO) as part of the mini-workshop "Ideals of Linear Subspaces, Their Symbolic Powers and Waring Problems" held in February 2015. Comments are welcome. Revised version corrects some typos, updates the references, and clarifies some hypotheses. To appear in the Journal of Algebraic Combinatoric

Human and Non-Human Primate Intestinal FcRn Expression and Immunoglobulin G Transcytosis

PURPOSE: To evaluate transcytosis of immunoglobulin G (IgG) by the neonatal Fc receptor (FcRn) in adult primate intestine to determine whether this is a means for oral delivery of monoclonal antibodies (mAbs). METHODS: Relative regional expression of FcRn and localization in human intestinal mucosa by RT-PCR, ELISA & immunohistochemistry. Transcytosis of full-length mAbs (sandwich ELISA-based detection) across human intestinal segments mounted in Ussing-type chambers, human intestinal (caco-2) cell monolayers grown in transwells, and serum levels after regional intestinal delivery in isoflurane-anesthetized cynomolgus monkeys. RESULTS: In human intestine, there was an increasing proximal-distal gradient of mucosal FcRn mRNA and protein expression. In cynomolgus, serum mAb levels were greater after ileum-proximal colon infusion than after administration to stomach or proximal small intestine (1–5 mg/kg). Serum levels of wild-type mAb dosed into ileum/proximal colon (2 mg/kg) were 124 ± 104 ng/ml (n = 3) compared to 48 ± 48 ng/ml (n = 2) after a non-FcRn binding variant. In vitro, mAb transcytosis in polarized caco-2 cell monolayers and was not enhanced by increased apical cell surface IgG binding to FcRn. An unexpected finding in primate small intestine, was intense FcRn expression in enteroendocrine cells (chromagranin A, GLP-1 and GLP-2 containing). CONCLUSIONS: In adult primates, FcRn is expressed more highly in distal intestinal epithelial cells. However, mAb delivery to that region results in low serum levels, in part because apical surface FcRn binding does not influence mAb transcytosis. High FcRn expression in enteroendocrine cells could provide a novel means to target mAbs for metabolic diseases after systemic administration

Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets.

AIMS/HYPOTHESIS: Ageing is a major risk factor for development of metabolic diseases such as type 2 diabetes. Identification of the mechanisms underlying this association could help to elucidate the relationship between age-associated progressive loss of metabolic health and development of type 2 diabetes. We aimed to determine molecular signatures during ageing in the endocrine pancreas. METHODS: Global gene transcription was measured in pancreatic islets isolated from young and old rats by Ilumina BeadChip arrays. Promoter DNA methylation was measured by Sequenom MassArray in 46 genes that showed differential expression with age, and correlations with expression were established. Alterations in morphological and cellular processes with age were determined by immunohistochemical methods. RESULTS: Age-related changes in gene expression were found at 623 loci (>1.5-fold, false discovery rate [FDR] <5%), with a significant (FDR < 0.05) enrichment in genes previously implicated in islet-cell function (Enpp1, Abcc8), type 2 diabetes (Tspan8, Kcnq1), inflammatory processes (Cxcl9, Il33) and extracellular matrix organisation (Col3a1, Dpt). Age-associated transcriptional differences negatively correlated with promoter DNA methylation at several loci related to inflammation, glucose homeostasis, cell proliferation and cell-matrix interactions (Il33, Cxcl9, Gpr119, Fbp2, Col3a1, Dpt, Spp1). CONCLUSIONS/INTERPRETATION: Our findings suggest that a significant proportion of pancreatic islets develop a low-grade 'chronic' inflammatory status with ageing and this may trigger altered functional plasticity. Furthermore, we identified changes in expression of genes previously linked to type 2 diabetes and associated changes in DNA methylation that could explain their age-associated dysregulation. These findings provide new insights into key (epi)genetic signatures of the ageing process in islets.Biotechnology and Biological Sciences Research Council (Grant ID: BB/H003312/1), British Heart Foundation, FP6 Epigenome Network of Excellence programme, GlaxoSmithKline, Nuffield Foundation, Royal Society, Medical Research Council (Grant ID: MRC_MC_UU_12012/4)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00125-015-3837-