On the physical origins of the negative index of refraction

The physical origins of negative refractive index are derived from a dilute microscopic model, producing a result that is generalized to the dense condensed phase limit. In particular, scattering from a thin sheet of electric and magnetic dipoles driven above resonance is used to form a fundamental description for negative refraction. Of practical significance, loss and dispersion are implicit in the microscopic model. While naturally occurring negative index materials are unavailable, ferromagnetic and ferroelectric materials provide device design opportunities.Comment: 4 pages, 1 figur

Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis?

Down's syndrome (DS, trisomy 21) represents a complex genetic abnormality that leads to pathology in later life that is similar to Alzheimer's disease (AD). We compared two cases of DS with APOE ε3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (Aβ42) burdens in the brain but that differed markedly in the severity of AD-like pathology. One exhibited extensive neurofibrillary pathology whereas the other showed minimal features of this type. Comparable loads of Aβ42 could relate to the cases' similar life-time accumulation of Aβ due to trisomy 21-enhanced metabolism of amyloid precursor protein (APP). The cases' significant difference in AD-like pathology, however, suggests that parenchymal deposition of Aβ42, even when extensive, may not inevitably trigger AD-like tau pathology (though it may be necessary). Thus, these observations of a natural experiment may contribute to understanding the nuances of the amyloid cascade hypothesis of AD pathogenesis

eIF4A Inhibition Allows Translational Regulation of mRNAs Encoding Proteins Involved in Alzheimer's Disease

Alzheimer's disease (AD) is the main cause of dementia in our increasingly aging population. The debilitating cognitive and behavioral symptoms characteristic of AD make it an extremely distressing illness for patients and carers. Although drugs have been developed to treat AD symptoms and to slow disease progression, there is currently no cure. The incidence of AD is predicted to increase to over one hundred million by 2050, placing a heavy burden on communities and economies, and making the development of effective therapies an urgent priority. Two proteins are thought to have major contributory roles in AD: the microtubule associated protein tau, also known as MAPT; and the amyloid-beta peptide (A-beta), a cleavage product of amyloid precursor protein (APP). Oxidative stress is also implicated in AD pathology from an early stage. By targeting eIF4A, an RNA helicase involved in translation initiation, the synthesis of APP and tau, but not neuroprotective proteins, can be simultaneously and specifically reduced, representing a novel avenue for AD intervention. We also show that protection from oxidative stress is increased upon eIF4A inhibition. We demonstrate that the reduction of these proteins is not due to changes in mRNA levels or increased protein degradation, but is a consequence of translational repression conferred by inhibition of the helicase activity of eIF4A. Inhibition of eIF4A selectively and simultaneously modulates the synthesis of proteins involved in Alzheimer's disease: reducing A-beta and tau synthesis, while increasing proteins predicted to be neuroprotective

Analytical approaches for transplant research

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73605/1/j.1600-6135.2004.00402.x.pd

Eimeria Species and Genetic Background Influence the Serum Protein Profile of Broilers with Coccidiosis

BACKGROUND: Coccidiosis is an intestinal disease caused by protozoal parasites of the genus Eimeria. Despite the advent of anti-coccidial drugs and vaccines, the disease continues to result in substantial annual economic losses to the poultry industry. There is still much unknown about the host response to infection and to date there are no reports of protein profiles in the blood of Eimeria-infected animals. The objective of this study was to evaluate the serum proteome of two genetic lines of broiler chickens after infection with one of three species of Eimeria. METHODOLOGY/PRINCIPAL FINDINGS: Birds from lines A and B were either not infected or inoculated with sporulated oocysts from one of the three Eimeria strains at 15 d post-hatch. At 21 d (6 d post-infection), whole blood was collected and lesion scoring was performed. Serum was harvested and used for 2-dimensional gel electrophoresis. A total of 1,266 spots were quantitatively assessed by densitometry. Protein spots showing a significant effect of coccidia strain and/or broiler genetic line on density at P<0.05-0.01 (250 spots), P<0.01-0.001 (248 spots), and P<0.001 (314 spots) were excised and analyzed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. Proteins were identified in 172 spots. A total of 46 different proteins were identified. Of the spots with a corresponding protein identification, 57 showed a main effect of coccidia infection and/or 2-way interaction of coccidia infection×broiler genetic line at P<0.001. CONCLUSIONS/SIGNIFICANCE: Several of the metabolic enzymes identified in this study are potential candidates for early diagnostic markers of E. acervulina infection including malate dehydrogenase 2, NADH dehydrogenase 1 alpha subcomplex 9, and an ATP synthase. These proteins were detected only in Line A birds that were inoculated with E. acervulina. Results from this study provide a basic framework for future research aimed at uncovering the complex biochemical mechanisms involved in host response to Eimeria infection and in identifying molecular targets for diagnostic screening and development of alternative preventative and therapeutic methods

Growing Environmental Activists: Developing Environmental Agency and Engagement Through Children’s Fiction.

We explore how story has the potential to encourage environmental engagement and a sense of agency provided that critical discussion takes place. We illuminate this with reference to the philosophies of John Macmurray on personal agency and social relations; of John Dewey on the primacy of experience for philosophy; and of Paul Ricoeur on hermeneutics, dialogue, dialectics and narrative. We view the use of fiction for environmental understanding as hermeneutic, a form of conceptualising place which interprets experience and perception. The four writers for young people discussed are Ernest Thompson Seton, Kenneth Grahame, Michelle Paver and Philip Pullman. We develop the concept of critical dialogue, and link this to Crick's demand for active democratic citizenship. We illustrate the educational potential for environmental discussions based on literature leading to deeper understanding of place and environment, encouraging the belief in young people that they can be and become agents for change. We develop from Zimbardo the key concept of heroic resister to encourage young people to overcome peer pressure. We conclude with a call to develop a greater awareness of the potential of fiction for learning, and for writers to produce more focused stories engaging with environmental responsibility and activism

Constraints on the Variations of the Fundamental Couplings

We reconsider several current bounds on the variation of the fine-structure constant in models where all gauge and Yukawa couplings vary in an interdependent manner, as would be expected in unified theories. In particular, we re-examine the bounds established by the Oklo reactor from the resonant neutron capture cross-section of 149Sm. By imposing variations in \Lambda_{QCD} and the quark masses, as dictated by unified theories, the corresponding bound on the variation of the fine-structure constant can be improved by about 2 orders of magnitude in such theories. In addition, we consider possible bounds on variations due to their effect on long lived \alpha- and \beta-decay isotopes, particularly 147Sm and 187Re. We obtain a strong constraint on \Delta \alpha / \alpha, comparable to that of Oklo but extending to a higher redshift corresponding to the age of the solar system, from the radioactive life-time of 187Re derived from meteoritic studies. We also analyze the astrophysical consequences of perturbing the decay Q values on bound state \beta-decays operating in the s-process.Comment: 25 pages, latex, 5 eps figure

Room-temperature cycling of metal fluoride electrodes: Liquid electrolytes for high-energy fluoride ion cells

Fluoride ion batteries are potential “next-generation” electrochemical storage devices that offer high energy density. At present, such batteries are limited to operation at high temperatures because suitable fluoride ion–conducting electrolytes are known only in the solid state. We report a liquid fluoride ion–conducting electrolyte with high ionic conductivity, wide operating voltage, and robust chemical stability based on dry tetraalkylammonium fluoride salts in ether solvents. Pairing this liquid electrolyte with a copper–lanthanum trifluoride (Cu@LaF_3) core-shell cathode, we demonstrate reversible fluorination and defluorination reactions in a fluoride ion electrochemical cell cycled at room temperature. Fluoride ion–mediated electrochemistry offers a pathway toward developing capacities beyond that of lithium ion technology

A qualitative study exploring the health-related quality of life and symptomatic experiences of adults and adolescents with ulcerative colitis

Background: Ulcerative colitis (UC) often first presents during adolescence and early adulthood. Primary symptoms of UC are well known, yet similarities and differences of disease experience in adults and adolescents are not well characterized. Methods: To understand the health-related quality of life (HRQoL) and symptomatic experience of UC, in-depth interviews were conducted in the US with 21 adults (20–70 years) and 14 adolescents (12–17 years). Eligibility and medical history were confirmed by clinician report. A previously conducted literature review and resultant conceptual model informed the discussion guide to explore symptoms and HRQoL. Age appropriate creative tasks (“animal” task and collage) were employed to facilitate discussion. Transcripts and collages were subjected to thematic analysis using ATLAS.ti software. Results: Clinician-reported UC severity included 24% mild, 38% moderate, 38% severe among adults; and 64% mild, 29% moderate, 7% severe among adolescents. Among adults, 52% were female, 67% were white. Among adolescents, 50% were female, 71% were white. During analysis it was noted that all participants reported stomach/abdominal pain. Other key symptoms identified were frequent bowel movements, diarrhea, blood in stools, sudden need for bowel movement, stomach cramping, bloating, and feeling gassy/passing gas (?75% of participants). Key impacts identified were embarrassment, dietary limitations, having to plan around UC, worry/fear, anger, low mood/depression, and relationship with others, (?75% of participants). In creative tasks, animals were chosen to represent their UC and content included in the collages reflected the most commonly discussed themes from the interviews. Only adults discussed feeling dehydrated, while only adolescents discussed the impact of UC on school life. Conclusions: Open-ended interviews highlighted the HRQoL and symptomatic experiences of UC from the patient’s perspective, which were similar between adult and adolescent UC patients