423 research outputs found
Debt enforcement and the return on money
The rate-of-return-dominance puzzle asks why low-return assets, like fiat money, are used in actual economies given that risk-free higher-return assets are available. As long as this question remains unresolved, most conclusions from monetary models which arbitrarily restrict the marketability properties of alternative assets to make money valuable are difficult to assess. In this paper, I provide a framework in which fiat money has value in equilibrium, even though a higher-return asset is available and there are neither restrictions nor transaction costs in using it. I suggest that the use of money is associated with frictions underlying debt contracts. In an environment where full enforcement is not feasible, the actual rate of return on assets is determined by incentives eliciting voluntary debt repayment. I show that the inflation rate or, more generally, the depreciation rate of an asset in which debts are denominated may function as a commitment device. As a result, money is used in equilibrium and the optimal inflation rate is positive.Money, Inflation, Debt Enforcement, Banking.
The Change in Factors Affecting Physician Choice of Practice Location: A Comparison of Younger and Older Rural and Metropolitan Physicians
This study uses multiple discriminant analysis to derive the factors that physicians deem important in their decisions about where to locate their medical practices. Older physicians are compared to younger physicians both within rural areas and within metropolitan areas. Three of the top four discriminating variables for the youngest doctors were influence of the preceptorship period, preference of the spouse, and the repayment of a forgiveness loan. For the oldest group of doctors, two of the top three discriminating variables were the opportunity to join a desirable two-person partnership, and the perception of a high medical need in the area
In Depth Insights into the Key Steps of Delamination of Charged 2D Nano Materials
Delamination is a key step to obtain individual layers from inorganic layered materials needed for fundamental studies and applications. For layered van-der-Waals materials like graphene the adhesion forces are small allowing for mechanical exfoliation, whereas for ionic layered materials like layered silicates the energy to separate adjacent layers is considerably higher. Quite counter intuitively, we show for a synthetic layered silicate (Na0.5-hectorite) that a scalable and quantitative delamination by simple hydration is possible for high and homogeneous charge density, even for aspect ratios as large as 20000. A general requirement is the separation of adjacent layers by solvation to a distance where layer interactions become repulsive (Gouy-Chapman length). Further hydration up to 34 nm leads to the formation of a highly ordered lamellar liquid crystalline phase (Wigner crystal). Up to 8 higher-order reflections indicate excellent positional order of individual layers. The Wigner crystal melts when the interlayer separation reaches the Debye length, where electrostatic interactions between adjacent layers are screened. The layers become weakly chargecorrelated. This is indicated by fulfilling the classical Hansen-Verlet and Lindeman criteria for melting. We provide insight into the requirements for layer separation and controlling the layer distances for a broad range of materials and outline an important pathway for the integration of layers into devices for advanced applications
Segregation by thermal diffusion of an intruder in a moderately dense granular fluid
A solution of the inelastic Enskog equation that goes beyond the weak
dissipation limit and applies for moderate densities is used to determine the
thermal diffusion factor of an intruder immersed in a dense granular gas under
gravity. This factor provides a segregation criterion that shows the transition
between the Brazil-nut effect (BNE) and the reverse Brazil-nut effect (RBNE) by
varying the parameters of the system (masses, sizes, density and coefficients
of restitution). The form of the phase-diagrams for the BNE/RBNE transition
depends sensitively on the value of gravity relative to the thermal gradient,
so that it is possible to switch between both states for given values of the
parameters of the system. Two specific limits are considered with detail: (i)
absence of gravity, and (ii) homogeneous temperature. In the latter case, after
some approximations, our results are consistent with previous theoretical
results derived from the Enskog equation. Our results also indicate that the
influence of dissipation on thermal diffusion is more important in the absence
of gravity than in the opposite limit. The present analysis extends previous
theoretical results derived in the dilute limit case [V. Garz\'o, Europhys.
Lett. {\bf 75}, 521 (2006)] and is consistent with the findings of some recent
experimental results.Comment: 10 figure
E.U. paediatric MOG consortium consensus: Part 4 – Outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders
There is increasing knowledge on the role of antibodies against myelin oligodendrocyte glycoprotein
(MOG-abs) in acquired demyelinating syndromes and autoimmune encephalitis in children. Better understanding and prediction of outcome is essential to guide treatment protocol decisions. Therefore, this
part of the Paediatric European Collaborative Consensus provides an oversight of existing knowledge of
clinical outcome assessment in paediatric MOG-ab-associated disorders (MOGAD). The large heterogeneity in disease phenotype, disease course, treatment and follow-up protocols is a major obstacle for
reliable prediction of outcome. However, the clinical phenotype of MOGAD appears to be the main
determinant of outcome. Patients with a transverse myelitis phenotype in particular are at high r
Selective Adsorption and Chiral Amplification of Amino Acids in Vermiculite Clay -Implications for the origin of biochirality
Smectite clays are hydrated layer silicates that, like micas, occur naturally
in abundance. Importantly, they have readily modifiable interlayer spaces that
provide excellent sites for nanochemistry. Vermiculite is one such smectite
clay and in the presence of small chain-length alkyl-NH3Cl ions, forms
sensitive, 1-D ordered model clay systems with expandable nano-pore inter-layer
regions. These inter-layers readily adsorb organic molecules. N-propyl NH3Cl
vermiculite clay gels were used to determine the adsorption of alanine, lysine
and histidine by chiral HPLC. The results show that during reaction with fresh
vermiculite interlayers, significant chiral enrichment of either L- and
D-enantiomers occurs depending on the amino acid. Chiral enrichment of the
supernatant solutions is up to about 1% per pass. In contrast, addition to clay
interlayers already reacted with amino acid solutions resulted in little or no
change in D/L ratio during the time of the experiment. Adsorption of small
amounts of amphiphilic organic molecules in clay inter-layers is known to
produce Layer-by-Layer or Langmuir-Blodgett films. Moreover atomistic
simulations show that self-organization of organic species in clay interlayers
is important. These non-centrosymmetric, chirally active nanofilms may cause
clays to act subsequently as chiral amplifiers, concentrating organic material
from dilute solution and having different adsorption energetics for D- and
L-enantiomers. The additional role of clays in RNA oligimerization already
postulated by Ferris and others, together with the need for the organization of
amphiphilic molecules and lipids noted by Szostak and others, suggests that
such chiral separation by clays in lagoonal environments at normal biological
temperatures might also have played a significant role in the origin of
biochirality.Comment: 17 Pages, 2 Figures, 4 Table
E.U. paediatric MOG consortium consensus: Part 4 - Outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders
There is increasing knowledge on the role of antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) in acquired demyelinating syndromes and autoimmune encephalitis in children. Better understanding and prediction of outcome is essential to guide treatment protocol decisions. Therefore, this part of the Paediatric European Collaborative Consensus provides an oversight of existing knowledge of clinical outcome assessment in paediatric MOG-ab-associated disorders (MOGAD). The large heterogeneity in disease phenotype, disease course, treatment and follow-up protocols is a major obstacle for reliable prediction of outcome. However, the clinical phenotype of MOGAD appears to be the main determinant of outcome. Patients with a transverse myelitis phenotype in particular are at high risk of accruing neurological disability (motor and autonomic), which is frequently severe. In contrast, having a single episode of optic neuritis any time during disease course is broadly associated with a lower risk of persistent disability. Furthermore, MOG-ab-associated optic neuritis often results in good functional visual recovery, although retinal axonal loss may be severe. The field of cognitive and behavioural outcome and epilepsy following demyelinating episodes has not been extensively explored, but in recent studies acute disseminated encephalomyelitis (-like) phenotype in the young children was associated with cognitive problems and epilepsy in long-term follow-up. In conclusion, main domains of importance in determining clinical outcome in paediatric MOGAD are visual, motor, autonomic and cognitive function. A standardised evaluation of these outcome domains in all children is of importance to allow adequate rehabilitation and follow-up
Renin inhibition by substituted piperidines: A novel paradigm for the inhibition of monomeric aspartic proteinases?
BackgroundThe aspartic proteinase renin catalyses the first and rate-limiting step in the conversion of angiotensinogen to the hormone angiotensin II, and therefore plays an important physiological role in the regulation of blood pressure. Numerous potent peptidomimetic inhibitors of this important drug target have been developed, but none of these compounds have progressed past clinical phase II trials. Limited oral bioavailability or excessive production costs have prevented these inhibitors from becoming new antihypertensive drugs. We were interested in developing new nonpeptidomimetic renin inhibitors.ResultsHigh-throughput screening of the Roche compound library identified a simple 3,4-disubstituted piperidine lead compound. We determined the crystal structures of recombinant human renin complexed with two representatives of this new class. Binding of these substituted piperidine derivatives is accompanied by major induced-fit adaptations around the enzyme's active site.ConclusionsThe efficient optimisation of the piperidine inhibitors was facilitated by structural analysis of the renin active site in two renin-inhibitor complexes (some of the piperidine derivatives have picomolar affinities for renin). These structural changes provide the basis for a novel paradigm for inhibition of monomeric aspartic proteinases
The molybdenum isotopic composition of the modern ocean
Natural variations in the isotopic composition of molybdenum (Mo) are showing increasing potential as a tool in geochemistry. Although the ocean is an important reservoir of Mo, data on the isotopic composition of Mo in seawater are scarce. We have recently developed a new method for the precise determination of Mo isotope ratios on the basis of preconcentration using a chelating resin and measurement by multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS), which allows us to measure every stable Mo isotope. In this study, 172 seawater samples obtained from 9 stations in the Pacific, Atlantic, and Southern Oceans were analyzed, giving global coverage and the first full depth-profiles. The average isotope composition in δA/95Mo (relative to a Johnson Matthey Mo standard solution) was as follows: δ92/95Mo = –2.54 ± 0.16‰ (2SD), δ94/95Mo = –0.73 ± 0.19‰, δ96/95Mo = 0.85 ± 0.07‰, δ97/95Mo = 1.68 ± 0.08‰, δ98/95Mo = 2.48 ± 0.10‰, and δ100/95Mo = 4.07 ± 0.18‰. The δ values showed an excellent linear correlation with atomic mass of AMo (R2 = 0.999). Three-isotope plots for the Mo isotopes were fitted with straight lines whose slopes agreed with theoretical values for mass-dependent isotope fractionation. These results demonstrate that Mo isotopes are both uniformly distributed and follow a mass-dependent fractionation law in the modern oxic ocean. A common Mo standard is urgently required for the precise comparison of Mo isotopic compositions measured in different laboratories. On the other hand, our results strongly support the possibility of seawater as an international reference material for Mo isotopic composition
A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models
In patients with type 2 diabetes, pancreatic beta cells progressively degenerate and gradually lose their ability to produce insulin and regulate blood glucose. Beta cell dysfunction and loss is associated with an accumulation of aggregated forms of islet amyloid polypeptide (IAPP) consisting of soluble prefibrillar IAPP oligomers as well as insoluble IAPP fibrils in pancreatic islets. Here, we describe a human monoclonal antibody selectively targeting IAPP oligomers and neutralizing IAPP aggregate toxicity by preventing membrane disruption and apoptosis in vitro. Antibody treatment in male rats and mice transgenic for human IAPP, and human islet-engrafted mouse models of type 2 diabetes triggers clearance of IAPP oligomers resulting in beta cell protection and improved glucose control. These results provide new evidence for the pathological role of IAPP oligomers and suggest that antibody-mediated removal of IAPP oligomers could be a pharmaceutical strategy to support beta cell function in type 2 diabetes
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