Miracle-dz/UniFAR-FTUs huggingface dataset:
STUDIES ON THE EFFECT OF THE CARRIER MOLECULE ON ANTIHAPTEN ANTIBODY SYNTHESIS

Equilibrium measurements of interactions of anti-DNP antibodies, prepared using DNP-PLL and several DNP-proteins for immunization, with DNP0.6-PLL240 and with the univalent hapten, ε-DNP-L-lysine, were made utilizing the technique of fluorescence quenching. Carrier specificity of anti-DNP-PLL antibodies was demonstrated by a higher average intrinsic association constant (K0) of anti-DNP-PLL antibodies with DNP0.6-PLL240 than with ε-DNP-L-lysine. The free energy contribution of the PLL carrier to the interaction of intact anti-DNP-PLL antibodies with DNP0.6-PLL240 was from –0.8 to –2.1 kcal/mole. On the other hand, intact anti-DNP-protein antibodies displayed a lower energy of interaction with DNP0.6-PLL240 than with ε-DNP-L-lysine of up to +2.4 kcal/mole. Fab' fragments of both anti-DNP-PLL and anti-DNP-BGG antibodies have K0's with ε-DNP-L-lysine identical to the K0's of the intact anti-DNP antibodies from which they were prepared. However, K0 of interaction of Fab' fragments with DNP0.6-PLL240 (a large proportion of the conjugated PLL molecules in this preparation bear more than one DNP group) is considerably lower than that of the intact antibody. Thus a cooperative effect in the binding of bivalent antibody and bivalent (or greater) antigen exists and is of the order of –1.2 to –2.0 kcal/mole of IgG antibody. Although the direct contribution of the carrier to the interaction of Fab' fragment of anti-DNP-PLL and DNP0.6-PLL240 is –0.4 kcal/mole, the energy of carrier specificity, based upon consideration of cooperative effects and of repulsion of anti-DNP-protein antibodies for portions of the DNP-PLL determinants, is of the order of –3 kcal/mole (approximately 30% of total binding energy).
Eurocoin: A Real Time Coincident Indicator of the Euro Area Business Cycle

This paper is the result of the Bank of Italy-CEPR project to construct a monthly coincident indicator of the business cycle of the euro area. The index is estimated on the basis of a harmonized data set of monthly statistics of the euro area (951 series) which we constructed from a variety of sources. We use the information of this large panel to obtain an indicator which has three characteristics: (i) it provides real time information on monthly coincident activity since it is updated as new information become available in a non-synchronous way; (ii) it is cleaned from noise originated from measurement error and idiosyncratic national and sectoral dynamics; (iii) it is cleaned from seasonal and short-run dynamics through a i? ½lter that requires very little revision at the end of the sample. Unlike other methods used in the literature, the procedure takes into consideration the cross-country as well as the within-country correlation structure and exploits all information on dynamic cross-correlations. As a byproduct of our analysis, we provide a characterization of the commonality and dynamic relations of the series in the data set with respect to the coincident indicator and a dating of the euro area cycle.
Analyses of Developmental Rate Isomorphy in Ectotherms: Introducing the Dirichlet Regression

Temperature drives development in insects and other ectotherms because their metabolic rate and growth depends directly on thermal conditions. However, relative durations of successive ontogenetic stages often remain nearly constant across a substantial range of temperatures. This pattern, termed ‘developmental rate isomorphy’ (DRI) in insects, appears to be widespread and reported departures from DRI are generally very small. We show that these conclusions may be due to the caveats hidden in the statistical methods currently used to study DRI. Because the DRI concept is inherently based on proportional data, we propose that Dirichlet regression applied to individual-level data is an appropriate statistical method to critically assess DRI. As a case study we analyze data on five aquatic and four terrestrial insect species. We find that results obtained by Dirichlet regression are consistent with DRI violation in at least eight of the studied species, although standard analysis detects significant departure from DRI in only four of them. Moreover, the departures from DRI detected by Dirichlet regression are consistently much larger than previously reported. The proposed framework can also be used to infer whether observed departures from DRI reflect life history adaptations to size- or stage-dependent effects of varying temperature. Our results indicate that the concept of DRI in insects and other ectotherms should be critically re-evaluated and put in a wider context, including the concept of ‘equiproportional development’ developed for copepods.
Dopamine Reuptake Inhibition in the Rostral Agranular Insular Cortex Produces Antinociception

We provide evidence for an antinociceptive effect of dopamine in the rat cerebral cortex that is mediated through descending nociceptive inhibition of spinal neurons. Injection of the dopamine reuptake inhibitor GBR-12935 in the rostral agranular insular cortex (RAIC), a cortical area that receives a dense dopaminergic projection and is involved in descending antinociception (Burkey et al., 1996), resulted in dose-dependent inhibition of formalin-induced nociceptive behavior, without any alteration of motor function. Injection of the dopamine reuptake inhibitor in the surrounding cortical areas had no effect on nociceptive behaviors. GBR-12935 also produced a reduction in noxious stimulus-induced c-fos expression in nociceptive areas of the spinal dorsal horn, suggesting that dopamine in the RAIC acts in part through descending antinociception. Electrophysiological recording from single wide dynamic range-type spinal dorsal horn neurons confirmed the descending nociceptive inhibitory effect. GBR-12935 in the RAIC significantly reduced neuronal responses evoked by noxious thermal stimulation of the skin, an effect that was reversed by local administration of the selective D1 receptor antagonist SCH-23390. Finally, administration of SCH-23390 alone in the RAIC decreased paw withdrawal latencies from noxious heat, suggesting that dopamine acts tonically in the cortex to inhibit nociception.
Is the Linné impact crater morphology influenced by the rheological layering on the Moon's surface? Insights from numerical modeling

Linné is a simple crater, with a diameter of 2.23 km and a depth of 0.52 km, located in northwestern Mare Serenitatis. Recent high‐resolution data acquired by the Lunar Reconnaissance Orbiter Camera revealed that the shape of this impact structure is best described by an inverted truncated‐cone. We perform morphometric measurements, including slope and profile curvature, on the Digital Terrain Model of Linné, finding the possible presence of three subtle topographic steps, at the elevation of +20, −100, and −200 m relative to the target surface. The kink at −100 m might be related to the interface between two different rheological layers. Using the iSALE shock physics code, we numerically model the formation of Linné crater to derive hints on the possible impact conditions and target physical properties. In the initial setup, we adopt a basaltic projectile impacting the Moon with a speed of 18 km s−1. For the local surface, we consider either one or two layers, in order to test the influence of material properties or composite rheologies on the final crater morphology. The one‐layer model shows that the largest variations in the crater shape take place when either the cohesion or the friction coefficient is varied. In particular, a cohesion of 10 kPa marks the threshold between conical‐ and parabolic‐shaped craters. The two‐layer model shows that the interface between the two layers would be exposed at the observed depth of 100 m when an intermediate value (~200 m) for the upper fractured layer is set. We have also found that the truncated‐cone morphology of Linné might originate from an incomplete collapse of the crater wall, as the breccia lens remains clustered along the crater walls, while the high‐albedo deposit on the crater floor can be interpreted as a very shallow lens of fallout breccia. The modeling analysis allows us to derive important clues on the impactor size (under the assumption of a vertical impact and collision velocity equal to the mean value), and on the approximate, large‐scale preimpact target properties. Observations suggest that these large‐scale material properties likely include some important smaller scale variations, disclosed as subtle morphological steps in the crater walls. Furthermore, the modeling results allow advancing some hypotheses on the geological evolution of the Mare Serenitatis region where Linné crater is located (unit S14). We suggest that unit S14 has a thickness of at least a few hundreds of meters up to about 400 m.
Oxygen-Insensitive Nitroreductases: Analysis of the Roles ofnfsA and nfsB in Development of Resistance to 5-Nitrofuran Derivatives in Escherichia coli

ABSTRACT Nitroheterocyclic and nitroaromatic compounds constitute an enormous range of chemicals whose potent biological activity has significant human health and environmental implications. The biological activity of nitro-substituted compounds is derived from reductive metabolism of the nitro moiety, a process catalyzed by a variety of nitroreductase activities. Resistance of bacteria to nitro-substituted compounds is believed to result primarily from mutations in genes encoding oxygen-insensitive nitroreductases. We have characterized thenfsA and nfsB genes of a large number of nitrofuran-resistant mutants of Escherichia coli and have correlated mutation with cell extract nitroreductase activity. Our studies demonstrate that first-step resistance to furazolidone or nitrofurazone results from an nfsA mutation, while the increased resistance associated with second-step mutants is a consequence of an nfsB mutation. Inferences made from mutation about the structure-function relationships of NfsA and NfsB are discussed, especially with regard to the identification of flavin mononucleotide binding sites. We show that expression of plasmid-carried nfsA and nfsB genes in resistant mutants restores sensitivity to nitrofurans. Among the 20 first-step and 53 second-step mutants isolated in this study, 65 and 49%, respectively, contained insertion sequence elements innfsA and nfsB. IS1 integrated in both genes, while IS30 and IS186 were found only in nfsA and IS2 and IS5 were observed only in nfsB. Insertion hot spots for IS30 and IS186 are indicated innfsA, and a hot spot for IS5 insertion is evident in nfsB. We discuss potential regional and sequence-specific determinants for insertion sequence element integration in nfsA and nfsB.
Post-Stroke Depression: Impact of Lesion Location and Methodological Limitations—A Topical Review

Post-stroke depression (PSD) affects approximately one-third of all stroke patients. It hinders rehabilitation and is associated with worse functional outcome and increased mortality. Since the identification of PSD is a significant clinical problem, clinicians and researchers have tried to identify predictors that indicate patients at risk of developing PSD. This also includes the research question whether there is an association between PSD and stroke lesion characteristics, e.g., lesion size and lesion location. Early studies addressing this question are largely limited by technical constraints and, thus, focused on simple lesion characteristics such as lesion side or proximity of the lesion to the frontal pole of the brain. More recent studies have addressed the impact of involvement of specific neuronal circuits in the stroke lesion. State-of-the-art methods of lesion symptom mapping to study PSD have only been applied to small patient samples. Overall, results are controversial and no clear pattern of stroke lesions associated with PSD has emerged, though there are findings suggesting that more frontal stroke lesions are associated with higher incidence of PSD. Available studies are hampered by methodological limitations, including drawbacks of lesion analysis methods, small sample size, and the issue of patient selection. These limitations together with differences in approaches to assess PSD and in methods of image analysis limit the comparability of results from different studies. To summarize, as of today no definite association between lesion location and PSD can be ascertained and the understanding of PSD rests incomplete. Further insights are expected from the use of modern lesion inference analysis methods in larger patient samples taking into account standardized assessment of possible confounding parameters, such as stroke treatment and reperfusion status.
Gamma-Ray Limits on Galactic 60Fe Nucleosynthesis and Implications on the Origin of the 26Al Emission

The Gamma-Ray Imaging Spectrometer recently observed the gamma-ray emission from the Galactic center region. We have detected the 1809 keV Galactic 26Al emission at a significance level of 6.8 σ but have found no evidence for emission at 1173 and 1332 keV, which is expected from the decay chain of the nucleosynthetic 60Fe. The isotopic abundances and fluxes are derived for different source distribution models. The resulting abundances are between 2.6±0.4 and 4.5±0.7 M for 26Al, and a 2 σ upper limit for 60Fe is between 1.7 and 3.1 M. The measured 26Al emission flux is significantly higher than that derived from the Compton Gamma Ray Observatory COMPTEL 1.8 MeV sky map. This suggests that a fraction of the 26Al emission may come from extended sources with low surface brightness that are invisible to COMPTEL. We obtain an60Fe/26Al flux ratio 2 σ upper limit of 0.14, which is slightly lower than the 0.16 predicted from current nucleosynthesis models assuming that Type II supernovae are the major contributors to the Galactic 26Al. Since the uncertainties in the predicted fluxes are large (up to a factor of 2), our measurement is still compatible with the theoretical expectations.
Evaluating the overheads of source-directed quality-of-service routing

Quality-of-service (QoS) routing satisfies application performance requirements and optimizes network resource usage but effective path-selection schemes require the distribution of link-state information, which can impose a significant burden on the bandwidth and processing resources in the network. We investigate the fundamental trade-off between network overheads and the quality of routing decisions in the context of the source-directed link-state routing protocols proposed for future IP and ATM networks. Through extensive simulation experiments with several representative network topologies and traffic patterns, we uncover the effects of stale link-state information, random fluctuations in traffic load, and variations of the link-cost metric on the routing and signalling overheads. The paper concludes by summarizing our key results as a list of guidelines for designing efficient quality-of-service routing policies in large backbone networks.
Lichen planus with lesions on the palms and/or soles: prevalence and clinicopathological study of 36 patients

According to the literature, palmoplantar lesions in lichen planus (LP) are uncommon, and do not usually have the classically described clinical morphology. The aim of this study was to evaluate the prevalence of palmoplantar lesions in LP and to describe the characteristic clinicopathological appearances of LP affecting palms and soles. Palmoplantar LP with accompanying skin involvement accounted for 26% of our cases. The presence of very pruriginous erythematous scaly and/or hyperkeratotic plaques, with well‐defined edges, located on the internal plantar arch, without involvement of the fingertips, and which usually disappear in a few months, is characteristic of palmoplantar LP. Histopathological examination shows the characteristic features of LP.
Conventional T-bet+Foxp3− Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection

Although interferon γ (IFN-γ) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine known to counteract IFN-γ effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-γ–secreting T-bet+Foxp3− T helper type 1 (Th1) cells were found to be the major producers of IL-10 in these animals. Further analysis revealed that the same IL-10+IFN-γγ population displayed potent effector function against the parasite while, paradoxically, also inducing profound suppression of IL-12 production by antigen-presenting cells. Although at any given time point only a fraction of the cells appeared to simultaneously produce IL-10 and IFN-γ, IL-10 production could be stimulated in IL-10−IFN-γ+ cells by further activation in vitro. In addition, experiments with T. gondii–specific IL-10+IFN-γ+ CD4 clones revealed that although IFN-γ expression is imprinted and triggered with similar kinetics regardless of the state of Th1 cell activation, IL-10 secretion is induced more rapidly from recently activated than from resting cells. These findings indicate that IL-10 production by CD4+ T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens.
Discriminatory Information Disclosure

We consider a price discrimination problem in which a seller has a single object for sale to a potential buyer. At the time of contracting, the buyer's private type is his incomplete private information about his value, and the seller can disclose additional private information to the buyer. We study the question of whether discriminatory information disclosure can be profitable to the seller under the assumption that, for the same disclosure policy, the amount of additional private information that the buyer can learn depends on his private type. In both discrete-type and continuous-type setting, we show that discriminatory disclosure can be optimal because, compared to full disclosure, it reduces the information rent accrued to private types of the buyer without much impact on the trade surplus. A complete characterization of the optimal discriminatory disclosure policy is provided in the discrete-type setting. We also establish sufficient conditions for the optimality of full information disclosure in the continuous-type setting.
The Effect of Sterile Acellular Dermal Matrix Use on Complication Rates in Implant-Based Immediate Breast Reconstructions

Background The use of acellular dermal matrix (ADM) in implant-based immediate breast reconstruction has been increasing. The current ADMs available for breast reconstruction are offered as aseptic or sterile. No published studies have compared aseptic and sterile ADM in implant-based immediate breast reconstruction. The authors performed a retrospective study to evaluate the outcomes of aseptic versus sterile ADM in implant-based immediate breast reconstruction. Methods Implant-based immediate breast reconstructions with ADM conducted between April 2013 and January 2016 were included. The patients were divided into 2 groups: the aseptic ADM (AlloDerm) group and the sterile ADM (MegaDerm) group. Archived records were reviewed for demographic data and postoperative complication types and frequencies. The complications included were infection, flap necrosis, capsular contracture, seroma, hematoma, and explantation for any cause. Results Twenty patients were reconstructed with aseptic ADM, and 68 patients with sterile ADM. Rates of infection (15.0% vs. 10.3%), flap necrosis (5.0% vs. 7.4%), capsular contracture (20.0% vs. 14.7%), seroma (10.0% vs. 14.7%), hematoma (0% vs. 1.5%), and explantation (10.0% vs. 8.8%) were not significantly different in the 2 groups. Conclusions Sterile ADM did not provide better results regarding infectious complications than aseptic ADM in implant-based immediate breast reconstruction.
Intrinsic Aerobic Capacity Sets a Divide for Aging and Longevity

Rationale: Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease. For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity. Objectives: Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis). Methods and Results: Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15, and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO2max), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P<0.001). VO2max, measured across adulthood was a reliable predictor of lifespan (P<0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca2+ handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (VO2), and lean body mass were all better sustained with age in rats bred for high aerobic capacity. Conclusions: These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and are useful for deeper mechanistic exploration of aging.
Understanding the Complex Pathobiology of High Pathogenicity Avian Influenza Viruses in Birds

Abstract Avian influenza (AI) viruses are a diverse group of viruses that can be divided into 144 subtypes, based on different combinations of the 16 hemagglutinin and nine neuraminidase subtypes, and two pathotypes (low and high pathogenicity [HP]), based on lethality for the major poultry species, the chicken. However, other criteria are important in understanding the complex biology of AI viruses, including host adaptation, transmissibility, infectivity, tissue tropism, and lesion, and disease production. Overall, such pathobiological features vary with host species and virus strain. Experimentally, HPAI viruses typically produce a similar severe, systemic disease with high mortality in chickens and other gallinaceous birds. However, these same viruses usually produce no clinical signs of infection or only mild disease in domestic ducks and wild birds. Over the past decade, the emergent HPAI viruses have shifted to increased virulence for chickens as evident by shorter mean death times and a greater propensity for massive disseminated replication in vascular endothelial cells. Importantly, the Asian H5N1 HPAI viruses have changed from producing inconsistent respiratory infections in 2-wk-old domestic ducks to some strains being highly lethal in ducks with virus in multiple internal organs and brain. However, the high lethality for ducks is inversely related to age, unlike these viruses in gallinaceous poultry, which are highly lethal irrespective of the host age. The most recent Asian H5N1 HPAI viruses have infected some wild birds, producing systemic infections and death. Across all bird species, the ability to produce severe disease and death is associated with high virus replication titers in the host, especially in specific tissues such as brain and heart.