Fiscal Decentralization and Public R&D Policy: A Country Panel Analysis

This paper presents a first analysis of the potential link between the level of fiscal decentralization of a country and its public investment in innovation. We present a theoretical model where a ‘benevolent government’ invests in R&D aiming at maximizing net income, and R&D results are subject to interregional knowledge spillovers. The model predicts that decentralization leads to a lower level of public spending on innovation, and to a lower share of basic research in the government R&D budget. These hypotheses are empirically tested using country aggregate data. The results provide empirical support to the mentioned hypotheses, as we find evidence that higher levels of both expenditure and revenue decentralization are associated with a lower intensity of basic research in public R&D and with a lower level of R&D spending. The strength of the evidence, however, is weakened by the small sample size and shortcomings of the indicators used in the analysis

Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation

Broadband distortion modeling in Lyman-α\alpha forest BAO fitting

In recent years, the Lyman-$\alpha$ absorption observed in the spectra of high-redshift quasars has been used as a tracer of large-scale structure by means of the three-dimensional Lyman-$\alpha$ forest auto-correlation function at redshift $z\simeq 2.3$, but the need to fit the quasar continuum in every absorption spectrum introduces a broadband distortion that is difficult to correct and causes a systematic error for measuring any broadband properties. We describe a $k$-space model for this broadband distortion based on a multiplicative correction to the power spectrum of the transmitted flux fraction that suppresses power on scales corresponding to the typical length of a Lyman-$\alpha$ forest spectrum. Implementing the distortion model in fits for the baryon acoustic oscillation (BAO) peak position in the Lyman-$\alpha$ forest auto-correlation, we find that the fitting method recovers the input values of the linear bias parameter $b_{F}$ and the redshift-space distortion parameter $\beta_{F}$ for mock data sets with a systematic error of less than 0.5\%. Applied to the auto-correlation measured for BOSS Data Release 11, our method improves on the previous treatment of broadband distortions in BAO fitting by providing a better fit to the data using fewer parameters and reducing the statistical errors on $\beta_{F}$ and the combination $b_{F}(1+\beta_{F})$ by more than a factor of seven. The measured values at redshift $z=2.3$ are $\beta_{F}=1.39^{+0.11\ +0.24\ +0.38}_{-0.10\ -0.19\ -0.28}$and$b_{F}(1+\beta_{F})=-0.374^{+0.007\ +0.013\ +0.020}_{-0.007\ -0.014\ -0.022}$(1$\sigma$, 2$\sigma$and 3$\sigma$ statistical errors). Our fitting software and the input files needed to reproduce our main results are publicly available.Comment: 28 pages, 15 figures, matches the published versio

Racotumomab: an anti=idiotype vaccine related to N=glycolyl=containing=gangliosides: Preclinical and clinical data

Neu-glycolyl (NeuGc)-containing gangliosides are attractive targets for immunotherapy with anti-idiotype mAbs, because these glycolipids are not normal components of the cytoplasmic membrane in humans, but their expression has been demonstrated in several human malignant tumors. Racotumomab is an anti-idiotype mAb specific to P3 mAb, an antibody which reacts to NeuGc-containing gangliosides, sulfatides, and other antigens expressed in tumors. Preparations containing racotumomab were able to induce a strong anti-metastatic effect in tumor-bearing mice. Different Phase I clinical trials have been conducted in patients with advanced melanoma, breast cancer, and lung cancer. The results of these clinical trials demonstrated the low toxicity and the high immunogenicity of this vaccine. The induced antibodies recognized and directly killed tumor cells expressing NeuGcGM3. A Phase II/III multicenter, controlled, randomized, double blind clinical trial was conducted to evaluate the effect of aluminum hydroxide-precipitated racotumomab vaccine in overall survival in patients with advanced non-small cell lung cancer. The clinical results of this study showed a significant clinical benefit in the patients who were treated with the anti-idiotype vaccine.Fil: Vazquez, Ana M.. Center of Molecular Immunology; CubaFil: Hernandez, Ana M.. Center of Molecular Immunology; CubaFil: Macias, Amparo. Center of Molecular Immunology; CubaFil: Montero, Enrique. Center of Molecular Immunology; CubaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Gomez, Roberto E.. Elea Laboratories; Argentin

Maternal infection during pregnancy aggravates the behavioral response to an immune challenge during adolescence in female rats

Prenatal and early postnatal infection have been associated with changes in microglial activity and the development of psychiatric disorders. Here, we investigated the effect of prenatal immune activation and postnatal immune challenge, alone and combined, on behavior and microglial cell density in female Wistar rats. Pregnant rats were injected with poly I:C to induce a maternal immune activation (MIA). Their female offspring were subsequently exposed to a lipopolysaccharide (LPS) immune challenge during adolescence. Anhedonia, social behavior, anxiety, locomotion, and working memory were measured with the sucrose preference, social interaction, open field, elevated-plus maze, and Y-maze test, respectively. Microglia cell density was quantified by counting the number of Iba-1 positive cells in the brain cortex. Female MIA offspring were more susceptible to the LPS immune challenge during adolescence than control offspring as demonstrated by a more pronounced reduction in sucrose preference and body weight on the days following the LPS immune challenge. Furthermore, only the rats exposed to both MIA and LPS showed long-lasting changes in social behavior and locomotion. Conversely, the combination MIA and LPS prevented the anxiety induced by MIA alone during adulthood. MIA, LPS, or their combination did not change microglial cell density in the parietal and frontal cortex of adult rats. The results of our study suggest that the maternal immune activation during pregnancy aggravates the response to an immune challenge during adolescence in female rats.</p

Assessment of antibodies in the upper and lower human respiratory tract at steady state and after respiratory viral infection

OBJECTIVES: There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings. METHODS: We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were determined in BAL and plasma to assess plasma exudation. RESULTS: IgG and IgA were readily detectable in BAL and NP swabs, albeit at different ratios, while IgM levels were low. The total amount of antibody recovered from NP swabs varied greatly between study participants. Accordingly, the levels of influenza HA-specific antibodies varied, and individuals with lower amounts of total Ig in NP swabs had undetectable levels of HA-specific Ig. Similarly, the total amount of antibody recovered from BAL varied between study participants. However, severely ill patients showed evidence of increased plasma exudation, which may confound analysis of their BAL samples for mucosal antibodies. CONCLUSION: Nasopharyngeal swabs collected for diagnostic purposes may have utility in assessing antibodies from the human nasal mucosa, but variability in sampling should be accounted for. BAL samples can be utilised to study antibodies from the lower respiratory tract, but the possibility of plasma exudation should be excluded

The ISLAndS project II: The Lifetime Star Formation Histories of Six Andromeda dSphs

The Initial Star formation and Lifetimes of Andromeda Satellites (ISLAndS) project uses Hubble Space Telescope imaging to study a representative sample of six Andromeda dSph satellite companion galaxies. The main goal of the program is to determine whether the star formation histories (SFHs) of the Andromeda dSph satellites demonstrate significant statistical differences from those of the Milky Way, which may be attributable to the different properties of their local environments. Our observations reach the oldest main sequence turn-offs, allowing a time resolution at the oldest ages of ~ 1 Gyr, which is comparable to the best achievable resolution in the MW satellites. We find that the six dSphs present a variety of SFHs that are not strictly correlated with luminosity or present distance from M31. Specifically, we find a significant range in quenching times (lookback times from 9 to 6 Gyr), but with all quenching times more than ~ 6 Gyr ago. In agreement with observations of Milky Way companions of similar mass, there is no evidence of complete quenching of star formation by the cosmic UV background responsible for reionization, but the possibility of a degree of quenching at reionization cannot be ruled out. We do not find significant differences between the SFHs of the three members of the vast, thin plane of satellites and the three off-plane dSphs. The primary difference between the SFHs of the ISLAndS dSphs and Milky Way dSph companions of similar luminosities and host distances is the absence of very late quenching (< 5 Gyr ago) dSphs in the ISLAndS sample. Thus, models that can reproduce satellite populations with and without late quenching satellites will be of extreme interest.Comment: 24 pages, 11 figures, 3 tables, submitted to the Ap

Measuring Social-Ecological Resilience Reveals Opportunities for Transforming Environmental Governance

Understanding the resilience of social-ecological systems can advance our ability to transform environmental governance and achieve ecologically sustainable and socially just outcomes. However, measuring this multidimensional emergent system property has been elusive. We translated theoretical principles of resilience into ecological and social metrics and used expert knowledge to assess how they have changed through three sequential governance regimes of the Pacific herring fishery in northwestern Canada. We showed a significant reduction in system-wide resilience between previous Indigenous and historical colonial governance regimes, and limited change with the onset of the latest environmental justice era. We also detected recent signs of recovery among several metrics of resilience, thereby signaling that this system exhibits the preconditions for governance transformation. Pinpointing the erosion and recovery of attributes that confer social-ecological resilience can reveal leverage points and highlight strategic pathways to enable deliberate transformation toward a more ecologically sustainable and socially just future

Temporal variability is a personalized feature of the human microbiome

Background: It is now apparent that the complex microbial communities found on and in the human body vary across individuals. What has largely been missing from previous studies is an understanding of how these communities vary over time within individuals. To the extent to which it has been considered, it is often assumed that temporal variability is negligible for healthy adults. Here we address this gap in understanding by profiling the forehead, gut (fecal), palm, and tongue microbial communities in 85 adults, weekly over 3 months. Results: We found that skin (forehead and palm) varied most in the number of taxa present, whereas gut and tongue communities varied more in the relative abundances of taxa. Within each body habitat, there was a wide range of temporal variability across the study population, with some individuals harboring more variable communities than others. The best predictor of these differences in variability across individuals was microbial diversity; individuals with more diverse gut or tongue communities were more stable in composition than individuals with less diverse communities. Conclusions: Longitudinal sampling of a relatively large number of individuals allowed us to observe high levels of temporal variability in both diversity and community structure in all body habitats studied. These findings suggest that temporal dynamics may need to be considered when attempting to link changes in microbiome structure to changes in health status. Furthermore, our findings show that, not only is the composition of an individual's microbiome highly personalized, but their degree of temporal variability is also a personalized feature

Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile