Miracle-dz/UniFAR-FTUs huggingface dataset:
A proposed structural model for amyloid fibril elongation: domain swapping forms an interdigitating beta-structure polymer.

We propose a model illustrating how proteins, which differ in their overall sequences and structures, can form the propagating, twisted beta-sheet conformations, characteristic of amyloids. Some cases of amyloid formation can be explained through a "domain swapping" event, where the swapped segment is either a beta-hairpin or an unstable conformation which can partially unfold and assume a beta-hairpin structure. As in domain swapping, here the swapped beta-hairpin is at the edge of the structure, has few (if any) salt bridges and hydrogen bonds connecting it to the remainder of the structure and variable extents of buried non-polar surface areas. Additionally, in both cases the swapped piece constitutes a transient "building block" of the structure, with a high population time. Whereas in domain swapping the swapped fragment has been shown to be an alpha-helix, loop, strand or an entire domain, but so far not a beta-hairpin, despite the large number of cases in which it was already detected, here swapping may involve such a structural motif. We show how the swapping of beta-hairpins would form an interdigitated, twisted beta-sheet conformation, explaining the remarkable high stability of the protofibril in vitro. Such a swapping mechanism is attractive as it involves a universal mechanism in proteins, critical for their function, namely hinge-bending motions. Our proposal is consistent with structural superpositioning of mutational variants. While the overall r.m.s.d. s of the wild-type and mutants are small, the proposed hinge-bending region consistently shows larger deviations. These larger deviations illustrate that this region is more prone to respond to the mutational changes, regardless of their location in the sequence or in the structure. Nevertheless, above all, we stress that this proposition is hypothetical, since it is based on assumptions lacking definitive experimental support.
Electric-field-induced localization and oscillatory electro-optical properties of semiconductor superlattices.

We show that the application of an electric field $F$ along the growth axis of a semiconductor superlattice results in a strong localization of the eigenstates, a blue shift of the optical-absorption edge, and the presence of oscillations periodic in ${F}^{\ensuremath{-}1}$. These unique electro-optical properties are derived here within the framework of a tight-binding description of the envelope functions and also from numerical solutions of the Schr\"odinger equation for a finite set of coupled quantum wells.
Near field acoustic holography with particle velocity transducers

Near field acoustic holography is usually based on measurement of the pressure. This paper describes an investigation of an alternative technique that involves measuring the normal component of the acoustic particle velocity. A simulation study shows that there is no appreciable difference between the quality of predictions of the pressure based on knowledge of the pressure in the measurement plane and predictions of the particle velocity based on knowledge of the particle velocity in the measurement plane. However, when the particle velocity is predicted close to the source on the basis of the pressure measured in a plane further away, high spatial frequency components corresponding to evanescent modes are not only amplified by the distance but also by the wave number ratio (kz∕k). By contrast, when the pressure is predicted close to the source on the basis of the particle velocity measured in a plane further away, high spatial frequency components are reduced by the reciprocal wave number ratio (k∕kz).
Endotoxin-Induced Platelet Activation in Human Whole Blood In Vitro

Summary The effect of purified bacterial endotoxin was studied on human platelets in vitro. In adding up to 1 μg/mL of a highly purified endotoxin, we found neither aggregation nor ATP release in heparinized or citrated human platelet-rich plasma. On the other hand, endotoxin at concentrations as low as a few ng/mL (as may be found in septic patients) caused platelet aggregation in both heparinized and citrated human whole blood, as monitored by change in impedance, free platelet count, and size. Unlike collagen, the platelet aggregation with endotoxin occurred after a long lag phase, developed slowly, and was rarely coupled with measurable release of ATP. The platelet aggregating effect of endotoxin was dose-dependent and modified by exposure of the endotoxin to ionizing radiation. Thus, the activation of human platelets by “solubilized” endotoxin in plasma requires the presence of other blood cells. We propose that the platelet effect is mediated by monocytes and/or neutrophils stimulated by endotoxin.
Vitamin B 12 serostatus in Colombian children and adult women: results from a nationally representative survey

Abstract Objective Vitamin B12 deficiency is associated with many adverse health outcomes and is highly prevalent worldwide. The present study assesses the prevalence of vitamin B12 deficiency and marginal deficiency in Colombian children and women and examines the sociodemographic correlates of serum vitamin B12 concentrations in these groups. Design Cross-sectional, nationally representative survey. Setting Colombia. Subjects Children <18 years old (n 7243), pregnant women (n 1781), and non-pregnant women 18–49 years old (n 499). Results The overall prevalence of vitamin B12 deficiency (serum vitamin B12<148 pmol/l) and marginal deficiency (serum vitamin B12=148–221 pmol/l) was, respectively, 6·6 % (95 % CI 5·2 %, 8·3 %) and 22·5 % (95 % CI 21·1 %, 23·9 %). Pregnant women had the highest prevalence of deficiency (18·9 %; 95 % CI 16·6 %, 21·5 %) compared with non-pregnant adult women (18·5 %; 95 % CI 4·4 %, 53·1 %) and children (2·8 %; 95 % CI 2·3 % %, 3·3 %). In multivariable analyses among children, mean serum vitamin B12 was positively associated with female sex (12 pmol/l higher compared with males; P=0·004), secondary or higher education of the household head (12 pmol/l higher compared with primary or less; P=0·009) and food security (21 pmol/l higher compared with severe food insecurity; P=0·003). In multivariable analyses among pregnant women, mean serum vitamin B12 was positively associated with education of the household head and inversely associated with living in the National territories, Eastern or Pacific regions. Conclusions The prevalence of vitamin B12 deficiency and marginal deficiency in Colombian women and children is substantial. The burden falls largely on adult women, those with lowest education and those living in the poorest, most rural regions of the country.
Both nuclear and cytoplasmic components are defective in oocytes of the B6.Y(TIR) sex-reversed female mouse.

In the mammalian gonadal primordium, activation of the Sry gene on the Y chromosome initiates a cascade of genetic events leading to testicular organization whereas its absence results in ovarian differentiation. An exception occurs when the Y chromosome of Mus musculus domesticus from Tirano, Italy (Y(TIR)), is placed on the C57BL/6J (B6) genetic background. The B6.Y(TIR) progeny develop only ovaries or ovotestes despite Sry transcription in fetal life. Consequently, the XY offspring with bilateral ovaries develop into apparently normal females, but their eggs fail to develop after fertilization. Our previous studies have shown that the primary cause of infertility can be attributed to oocytes rather than their surrounding somatic cells in the XY ovary. This study attempted to identify the defects in oocytes from the B6.Y(TIR) female mouse. We examined the developmental potential of embryos from XY and XX females after exchanging their nuclear components by microsurgery following in vitro maturation and fertilization. The results suggest that both nuclear and cytoplasmic components are defective in oocytes from XY females. In the XY fetal ovary, most germ cells entered meiosis and their autosomes appeared to synapse normally while the X and Y chromosomes remained unpaired during meiotic prophase. This lack of X-Y pairing probably caused aneuploidy in some secondary oocytes following in vitro maturation. However, normal numbers of chromosomes in the rest of the secondary oocytes indicate that aneuploidy alone can not explain the nuclear defect in oocytes.
The Dangers of an Extended Period of Low Interest Rates: Why the Bank of Canada Should Start Raising Them Now

Interest rates in Canada and in many other countries have not been so low since the Great Depression. When taking into account inflation, short-term interest rates are negative in most developed countries, including Canada where the overnight rate currently stands at 1 percent in nominal terms. These historically low rates were initially a response to the global financial crisis that broke out in 2008. The financial crisis led to a sharp fall in economic activity, a dislocation of the financial system, and the need in many countries to recapitalize banks with public money. Output growth has resumed in the United States, but unemployment remains unsatisfactorily high. In the European Union, the recovery has been hampered by high public debt and fears of a breakdown of the euro area. Canada however does not face the same problems as either the United States or the EU. Its financial system was exposed to a much lesser extent to complicated sub-prime, mortgage-backed securities, and its economic difficulties are nowhere near as pronounced. The current downturn of output compared with its potential, although significant, has been less severe in Canada, and gross domestic product (GDP) has returned to a value closer to the economy’s capacity. In this Commentary, I argue that short-term rates are therefore too low in Canada, a situation that is starting to build in pervasive problems for the economy. Below-equilibrium interest rates for an extended period distort investment decisions, leading to excessive risk taking and inefficient and ultimately unprofitable investments. They also encourage the formation of asset bubbles whose collapse could lead to a recurrence of the recent financial crisis. Some of the symptoms of inefficient investment and asset price bubbles are already evident in Canada, in the housing sector for instance. The cumulative effect of artificially low interest rates also risks fuelling an underlying inflationary process. Therefore, I recommend that the Bank of Canada start now to reverse some of the monetary stimulus and begin raising interest rates.
The impact of unstable aids on consumption volatility in developing countries

In recent years, a large and expanding literature has examined the properties of developing economies with regard to the macroeconomic cycle.1 One such property that is characteristic of developing economies is large fluctuations in consumption.Meanwhile, aid for the low income countries is extremely volatile, and under certain circumstances, the volatile aid amplifies the consumption volatility. This document examines whether it is possible that the volatile aid yields high consumption volatility in African countries that constitute the majority of the low income countries. Our numerical analysis reveals that the strongly influential aid disbursements yield a considerably large fluctuation in consumption.
Ciclos Político-Econômicos e Regras Fiscais em Municípios Paranaenses Selecionados

O objetivo do artigo e avaliar se a Lei de Responsabilidade Fiscal (LRF) minimizou os efeitos dos ciclos politico-economicos nos municipios paranaenses com populacao superior a 150 mil habitantes. A hipotese que norteia a pesquisa e de que, com a ausencia de regras para o gasto com investimento, os ciclos politicos continuam ocorrendo, mesmo apos a implementacao da LRF. O principal resultado da pesquisa e que a alocacao orcamentaria, resultado do ciclo politico, pode ser uma resposta ao aumento na divida dos municipios analisados. Uma vez que a LRF tenha definido regras apenas com relacao aos gastos com pessoal, e imposto limitacoes na divida dos municipios na proporcao de 1,2 vezes da receita corrente liquida dos mesmos, tais entes federativos foram estimulados a fazer uso dos gastos com investimento para fins politicos, negligenciando o grau de comprometimento das receitas com o pagamento de juros e amortizacao da divida.
Thermodynamic Modeling for Open Combined Regenerative Brayton and Inverse Brayton Cycles with Regeneration before the Inverse Cycle

A thermodynamic model of an open combined regenerative Brayton and inverse Brayton cycles with regeneration before the inverse cycle is established in this paper by using thermodynamic optimization theory. The flow processes of the working fluid with the pressure drops and the size constraint of the real power plant are modeled. There are 13 flow resistances encountered by the working fluid stream for the cycle model. Four of these, the friction through the blades and vanes of the compressors and the turbines, are related to the isentropic efficiencies. The remaining nine flow resistances are always present because of the changes in flow cross-section at the compressor inlet of the top cycle, regenerator inlet and outlet, combustion chamber inlet and outlet, turbine outlet of the top cycle, turbine outlet of the bottom cycle, heat exchanger inlet, and compressor inlet of the bottom cycle. These resistances associated with the flow through various cross-sectional areas are derived as functions of the compressor inlet relative pressure drop of the top cycle, and control the air flow rate, the net power output and the thermal efficiency. The analytical formulae about the power output, efficiency and other coefficients are derived with 13 pressure drop losses. It is found that the combined cycle with regenerator can reach higher thermal efficiency but smaller power output than those of the base combined cycle at small compressor inlet relative pressure drop of the top cycle.
The burden of treatment failure in type 2 diabetes.

OBJECTIVE In type 2 diabetes, therapies to maintain blood glucose control usually fail after several years. We estimated the glycemic burden that accumulates from treatment failure and describe the time course and predictors of failure. RESEARCH DESIGN AND METHODS A prospective, population-based study using retrospective observational data. We identified all 7208 complete courses of treatment with nondrug therapy, sulfonylurea monotherapy, metformin monotherapy, and combination oral antihyperglycemic therapy between 1994 and 2002, inclusive, among members of the Kaiser Permanente Northwest Region. We calculated mean cumulative glycemic burden, defined as HbA(1c)-months >8.0 or 7.0% for each treatment. We then measured the likelihood that the next HbA(1c) would exceed 8.0 and 7.0% after HbA(1c) exceeded each of ten hypothetical treatment thresholds. Finally, we estimated multivariate logistic regression models to predict when HbA(1c) would continue to deteriorate. RESULTS In this well-controlled population, the average patient accumulated nearly 5 HbA(1c)-years of excess glycemic burden >8.0% from diagnosis until starting insulin and about 10 HbA(1c)-years of burden >7.0%. Whenever patients crossed the American Diabetes Association-recommended treatment threshold of 8.0%, their next HbA(1c) result was as likely to be <8.0 as >8.0%. Multivariate prediction models had highly statistically significant coefficients, but predicted <10% of the variation in future HbA(1c) results. CONCLUSIONS Clinicians should change glucose-lowering treatments in type 2 diabetes much sooner or use treatments that are less likely to fail. An action point at 7.0% or lower is more likely to prevent additional deterioration than the traditional action point of 8.0%.
The economic limits to modern politics: International liberalism reconsidered

World politics both creates opportunities for modern governments and imposes constraints on the range of actions that it is feasible for them to pursue. One way to think about these opportunities and constraints is to analyze the operation of the contemporary international political–military system, or the world political economy, and to consider how these systems affect state action. Much of the modern study of international relations is devoted to this task. Yet another perspective on the impact of world politics on states can be gained by asking how perceptive observers of politics have reflected on these issues in the past. This approach, which looks to the history of political thought for insights into contemporary international affairs, will be pursued here. Although the form and intensity of the constraints and opportunities created by the contemporary world system are different from those in earlier centuries, the impact of international politics and economics on state action has been evident for a long time, and has occasioned a great deal of sophisticated commentary. At some risk of blurring differences between thinkers of broadly similar inclinations, three major Western schools of thought on this subject can be identified: Marxist, realist and liberal. Each has been influential, although it is probably fair to say that realism has been the creed of Continental European statesmen for centuries, and that since World War II it has been predominant in the United States as well.
Leptin in Maternal Serum and Breast Milk: Association With Infants' Body Weight Gain in a Longitudinal Study Over 6 Months of Lactation

The adipokine leptin has been detected in human breast milk, but its effect on postnatal growth and development remains largely unclear. We hypothesized that leptin could affect infant's body weight gain during early lactation in the first 6 mo of life. Therefore, we evaluated leptin levels in maternal serum and breast milk of 23 healthy, lactating mothers and their neonates in a prospective, longitudinal study. Leptin concentration was quantified by a commercially available human leptin RIA. Our results showed that leptin levels in breast milk were 22-fold lower than in maternal serum, but both parameters were positively correlated to each other (r = 0.431, p = 0.001) and to maternal BMI (serum: r = 0.512, p < 0.001; milk: r = 0.298, p < 0.001) over 6 mo of lactation. A negative association was found between breast milk leptin levels during the first week after delivery and the infant weight gain from the end of the first to the sixth month (r = −0.681, p = 0.007). This suggests that milk-borne leptin provides a link between maternal body composition and infant growth and development and plays a critical role in regulating appetite and food intake during early infancy.
DETERMINANTS OF FOOD SECURITY IN SOUTHERN ETHIOPIA

The study investigates the relative importance of supply-side and demand-side factors of household food security through a logistic regression analysis applied to data collected from 247 sample households in Southern Ethiopia. Among the nine factors included in the model, seven were identified as statistically significant determinants of household food security: technological adoption, farming system, farm size, land quality, household size, per capita aggregate production and access to market. Among these, technological adoption, farming system, farm size, and land quality are supply-side factors. Household size, per capita aggregate production, and access to market are demand-side factors. Based on the magnitude of their partial effects on the probability of food security, supply-side factors are more powerful than the demand-side factors in determining household food security, implying that interventions focused on these factors need to get priority attention by policy, research and extension.
A Reconsideration of Uncovered Interest Rate Parity under Switching Policy Regimes

It is shown that when monetary authorities manage the interest rate through anti-inflationary policy rules which allow for occasional discrete shifts, then a Markov switching regimes representation is appropriate for the exchange rate and the interest rate differential series. In this setting, tests of the uncovered interest rate parity (UIP) hypothesis, based on the cross-equation restrictions on the parameters of a Markov switching regimes representation for the underlying variables, show that the interest parity relationship is not rejected 144 D.G. Kirikos for the currencies of Germany and the U.K. vis-a-vis the U.S. dollar over the period 1973-1997. These results suggest that previously reported failures of UIP may be the outcome of rational forecast errors induced by central bank interventions.
Two-dimensional Blue Native/SDS Gel Electrophoresis of Multi-Protein Complexes from Whole Cellular Lysates

Identification and characterization of multi-protein complexes is an important step toward an integrative view of protein-protein interaction networks that determine protein function and cell behavior. The limiting factor for identifying protein complexes is the method for their separation. Blue native PAGE (BN-PAGE) permits a high-resolution separation of multi-protein complexes under native conditions. To date, BN-PAGE has only been applicable to purified material. Here, we show that dialysis permits the analysis of multi-protein complexes of whole cellular lysates by BN-PAGE. We visualized different multi-protein complexes by immunoblotting including forms of the eukaryotic proteasome. Complex dynamics after γ interferon stimulation of cells was studied, and an antibody shift assay was used to detect protein-protein interactions in BN-PAGE. Furthermore, we identified defined protein complexes of various proteins including the tumor suppressor p53 and c-Myc. Finally, we identified multi-protein complexes via mass spectrometry, showing that the method has a wide potential for functional proteomics.
Bilateral lesions of nucleus subpretectalis/interstitio-pretecto-subpretectalis (SP/IPS) selectively impair figure–ground discrimination in pigeons

Abstract Earlier, we reported that nucleus rotundus (Rt) together with its inhibitory complex, nucleus subpretectalis/interstitio-pretecto-subpretectalis (SP/IPS), had significantly higher activity in pigeons performing figure–ground discrimination than in the control group that did not perform any visual discriminations. In contrast, color discrimination produced significantly higher activity than control in the Rt but not in the SP/IPS. Finally, shape discrimination produced significantly lower activity than control in both the Rt and the SP/IPS. In this study, we trained pigeons to simultaneously perform three visual discriminations (figure–ground, color, and shape) using the same stimulus displays. When birds learned to perform all three tasks concurrently at high levels of accuracy, we conducted bilateral chemical lesions of the SP/IPS. After a period of recovery, the birds were retrained on the same tasks to evaluate the effect of lesions on maintenance of these discriminations. We found that the lesions of the SP/IPS had no effect on color or shape discrimination and that they significantly impaired figure–ground discrimination. Together with our earlier data, these results suggest that the nucleus Rt and the SP/IPS are the key structures involved in figure–ground discrimination. These results also imply that thalamic processing is critical for figure–ground segregation in avian brain.