Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Cross-Interaction between APOE and PRNP in Sporadic Alzheimer's and Creutzfeldt-Jakob Diseases

Alzheimer's disease (AD) and Creutzfeldt-Jakob disease (CJD) represent two distinct clinical entities belonging to a wider group, generically named as conformational disorders that share common pathophysiologic mechanisms. It is well-established that the APOE ε4 allele and homozygosity at polymorphic codon 129 in the PRNP gene are the major genetic risk factors for AD and human prion diseases, respectively. However, the roles of PRNP in AD, and APOE in CJD are controversial. In this work, we investigated for the first time, APOE and PRNP genotypes simultaneously in 474 AD and 175 sporadic CJD (sCJD) patients compared to a common control population of 335 subjects. Differences in genotype distribution between patients and control subjects were studied by logistic regression analysis using age and gender as covariates. The effect size of risk association and synergy factors were calculated using the logistic odds ratio estimates. Our data confirmed that the presence of APOE ε4 allele is associated with a higher risk of developing AD, while homozygosity at PRNP gene constitutes a risk for sCJD. Opposite, we found no association for PRNP with AD, nor for APOE with sCJD. Interestingly, when AD and sCJD patients were stratified according to their respective main risk genes (APOE for AD, and PRNP for sCJD), we found statistically significant associations for the other gene in those strata at higher previous risk. Synergy factor analysis showed a synergistic age-dependent interaction between APOE and PRNP in both AD (SF = 3.59, p = 0.027), and sCJD (SF = 7.26, p = 0.005). We propose that this statistical epistasis can partially explain divergent data from different association studies. Moreover, these results suggest that the genetic interaction between APOE and PRNP may have a biological correlate that is indicative of shared neurodegenerative pathways involved in AD and sCJD.
Convergent Multiplicative Processes Repelled from Zero: Power Laws and Truncated Power Laws

Levy et Solomon ont montre qu'un processus multiplicatif du type ωt = λ 1 λ 2 . λ t (avec λ j > 0) conduit, en presence d'une contrainte de bord, a une distribution P(ωt) en loi de puissance ω t -(1+μ) . Nous proposons une derivation simple, intuitive et exacte de ce resultat basee sur une analogie avec une marche aleatoire. Nous obtenons les resultats suivants: 1) le regime de loi de puissance decrit la distribution asymptotique de w t aux grands temps et doit etre distingue du theoreme limite central decrivant la convergence de la variable reduite 1/√t(log ω t - (log ω t )) vers la loi Gaussienne; 2) les deux conditions necessaires et suffisantes pour que P(ω t ) soit une loi de puissance sont (log λ j ) < 0 (correspondant a une derive vers zero) et la contrainte que ω t soit empechee de trop s'approcher de zero. Cette contrainte peut etre mise en oeuvre de maniere variee, generalisant a une grande classe de modeles le cas d'une barriere reflechissante examine par Levy et Solomon. Nous donnons aussi un traitement approximatif, devenant exact dans la limite ou la distribution de λ est etroite ou log-normale en terme d'equation de Fokker-Planck. 3) Pour tous ces modeles, nous obtenons le resultat general la limite ou la distribution de λ est etroite ou log-normale en terme d'equatione de Fokker-Planck. 3) Pour tous ces modeles, nous obtenons le resultat general exact que l'exposant μ est la solution de l'equation (λ μ ) = 1. μ est donc non-universel et depend de la specificite de la distribution de λ. 4) Pour des t finis, la loi de puissance est tronquee par une queue log-normale due a une exploration finie de la marche aleatoire.
Kinematic constraints on the stellar and dark matter content of spiral and S0 galaxies

We present mass models of a sample of 14 spiral and 14 SO galaxies that constrain their stellar and dark matter content. For each galaxy, we derive the stellar mass distribution from near-infrared photometry under the assumptions of axisymmetry and a constant K s -band stellar mass-to-light ratio (M/L) Ks . To this we add a dark halo assumed to follow a spherically symmetric Navarro, Frenk and White profile and a correlation between concentration and dark mass within the virial radius, M DM . We solve the Jeans equations for the corresponding potential under the assumption of constant anisotropy in the meridional plane, β z . By comparing the predicted second velocity moment to observed long-slit stellar kinematics, we determine the three best-fitting parameters of the model: (M/L) Ks . M DM and β z . These simple axisymmetric Jeans models are able to accurately reproduce the wide range of observed stellar kinematics, which typically extend to ≈2-3R e or, equivalently, ≈0.5-1R 25 . Although our sample contains barred galaxies, we argue a posteriori that the assumption of axisymmetry does not significantly bias our results. We find a median stellar mass-to-light ratio at K s -band of 1.09 (M/L) Ks ,⊙ with an rms scatter of 0.31. We present preliminary comparisons between this large sample of dynamically determined stellar mass-to-light ratios and the predictions of stellar population models. The stellar population models predict slightly lower mass-to-light ratios than we measure. The mass models contain a median of 15 per cent dark matter by mass within an effective radius R e (defined here as the semimajor axis of the ellipse containing half the K s -band light) and 49 per cent within the optical radius R 25 . Dark and stellar matter contribute equally to the mass within a sphere of radius 4.1 R e or 1.0 R 25 . There is no evidence of any significant difference in the dark matter content of the spirals and S0s in our sample. Models without dark matter are also able to satisfactorily reproduce the observed kinematics in most cases. The improvement when a halo is added is statistically significant, however, and the stellar mass-to-light ratios of mass models with dark haloes match the independent expectations of stellar population models better.
The Impact of Outward FDI on the Performance of Chinese Multinationals

Using a new firm-level database, EMENDATA, this paper investigates the effects on Chinese multinational enterprises of Outward FDI (OFDI) into advanced European countries. Propensity score matching is combined with a difference-in-difference estimator to reduce the problems of self-selection of treated firms in foreign markets and to eliminate time-invariant and unobservable differences between those firms and the controls. The results provide robust evidence in support of the view that China’s OFDI had so far a positive impact on domestic activities in enhancing firms’ productivity and scales of operation, as measured by assets, sales and employment. Distinguishing among such investments on the basis of entry mode shows that acquisitions facilitate early access to intangible assets but are detrimental to financial performance, whereas greenfield investments have a positive impact on the scale and productivity of Chinese investors. Publication keywords: outward FDI, reverse spillovers, performance, Chinese multinationals
Administration of antimicrobials via the respiratory tract for the treatment of patients with nosocomial pneumonia: a meta-analysis.

BACKGROUND Aerosolized antibiotics are a widely recognized treatment for patients with cystic fibrosis (CF). We sought to clarify their role in the treatment of non-CF patients with nosocomial pneumonia by performing a meta-analysis of randomized controlled trials (RCTs) that compared administration of antimicrobials via the respiratory tract (with or without concurrent usage of systemic antibiotics) with control treatment. METHODS An extensive search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, Current Contents and bibliographies from retrieved publications was made. RESULTS Five RCTs were included in the meta-analysis. Administration of antimicrobials via respiratory tract (either inhaled or endotracheally instilled) as opposed to control was associated with better treatment success in intention-to-treat [fixed effect model: odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.29-4.44; random effects model: OR = 2.75, 95% CI 1.06-7.17] and in clinically evaluable patients (fixed effect model: OR = 3.14, 95% CI 1.48-6.70; random effects model: OR = 3.07, 95% CI 1.15-8.19). There were no statistically significant differences between therapeutic regimens regarding all-cause mortality (fixed effect model: OR = 0.84, 95% CI 0.43-1.64; random effects model: OR = 0.71, 95% CI 0.27-1.88), microbiological success (fixed effect model: OR = 2.06, 95% CI 0.91-4.68; random effects model: OR = 2.23, 95% CI 0.64-7.71) and toxicity (fixed effect model: OR = 0.34, 95% CI 0.04-2.53; random effects model: OR = 0.36, 95% CI 0.04-3.16). CONCLUSIONS The limited available evidence seems not to preclude a benefit from the administration of antimicrobial agents via the respiratory tract for treating nosocomial pneumonia.
The Neuronal Replicator Hypothesis

We propose that replication (with mutation) of patterns of neuronal activity can occur within the brain using known neurophysiological processes. Thereby evolutionary algorithms implemented by neuro- nal circuits can play a role in cognition. Replication of structured neuronal representations is assumed in several cognitive architectures. Replicators overcome some limitations of selectionist models of neuronal search. Hebbian learning is combined with replication to structure exploration on the basis of associations learned in the past. Neuromodulatory gating of sets of bistable neurons allows patterns of activation to be copied with mutation. If the probability of copying a set is related to the utility of that set, then an evolutionary algorithm can be implemented at rapid timescales in the brain. Populations of neuronal replicators can undertake a more rapid and stable search than can be achieved by serial modification of a single solution. Hebbian learning added to neuronal replication allows a powerful structuring of variability capable of learning the location of a global optimum from multiple previously visited local optima. Replication of solutions can solve the problem of catastrophic forgetting in the stability-plasticity dilemma. In short, neuronal replication is essential to explain several features of flexible cognition. Predictions are made for the experimental validation of the neuronal replicator hypothesis.
A Century of Temperature Variability in Lake Superior

A 100-yr-long time series of water temperature measured just downstream of Lake Superior is used to produce proxy time series of open-lake temperature. This analysis suggests that open-water Lake Superior summer temperatures have increased by roughly 3.5uC over the last century, most of that warming occurring in the last three decades. Correspondingly, the length of the positively stratified season has increased from 145 d to 170 d. The observed amount of warming is greater than the observed change in regional temperature over the same time period by roughly a factor of two. The discrepancy can be understood in the context of reduced winter ice cover, and implies that spatially and temporally averaged ice cover in Lake Superior has decreased from 23% to 12% over the last century. Global average air temperatures have recently warmed beyond their natural limits in historic atmospheric records (IPCC 2007). However, the expected response of temperature of oceans and other water bodies is less clear. Water temperatures of large natural systems may respond to the atmospheric warming trend in unexpected ways, due to nonlinearities, geographic variability, and feedback mechanisms. Unlike air temperature records, such as the Goddard Institute for Space Science (GISS) database (Hansen et al. 1999), reliable century-scale records of measured water temperature are exceedingly rare (Nixon et al. 2004); long, continuous records in lakes more so. Some analyses of lake-water temperature trends over nearly a century have been performed in the hypolimnetic waters of tropical lakes such as Lake Tanganyika (O'Reilly et al. 2003; Verburg et al. 2003) and Lake Malawi (Vollmer et al. 2005). Due to the absence of strong seasonal variation in surface heat flux and a lack of seasonal overturn, the deep water of these lakes respond gradually, and roughly proportionally, to changes in climate, and can be reliably analyzed using relatively temporally sparse data. In contrast, mid-latitude lakes with large inter-annual and annual variability compared to the magnitude of a long-term trend (for instance, the Laurentian Great Lakes), require dense temporal coverage in order to extract a statistically significant trend. These sorts of long time series are especially important in large lakes, since it has been shown (Austin and Colman 2007) that the thermal response of a complex system like a large, seasonally ice-covered lake can significantly exceed the rate of temperature change experienced by the regional atmospheric climate. This can be explained in terms of a coincident reduction of …
C1q Governs Deposition of Circulating Immune Complexes and Leukocyte Fcγ Receptors Mediate Subsequent Neutrophil Recruitment

Inflammation induced by circulating immunoglobulin G–immune complexes (ICs) characterizes many immune-mediated diseases. In this work, the molecular requirements for the deposition of circulating ICs and subsequent acute leukocyte recruitment in mice were elucidated. We show that after intravenous injection, preformed soluble ICs are rapidly deposited in the postcapillary venules of the cremaster microcirculation, secondary to increased vascular permeability. This deposition is dependent on complement C1q. IC deposition is associated with leukocyte recruitment. Leukocyte rolling, which is mediated by P-selectin in the exteriorized cremaster muscle, is not further increased in response to ICs. In contrast, leukocyte rolling velocity is significantly decreased and leukocyte adhesion is significantly increased in the presence of ICs. The IC-mediated slow leukocyte rolling velocity and subsequent adhesion and emigration are dependent on Fcγ receptors (FcγRs), particularly FcγRIII, with complement C3 and C5 having no detectable role. These studies suggest a regulatory mechanism of IC deposition and leukocyte trafficking in IC-mediated inflammation requiring C1q and FcγRs in sequential, noninteracting roles.
Phenotypic and Genotypic Characterization of Extended Spectrum β-Lactamase Klebsiella pneumoniae and Fluorescent Pseudomonas spp. Strains from Market Garden Products and Their Watering Water in Benin (West Africa)

Market garden products can carry several types of microorganisms, and their consumption is the source of many cases of food poisoning. This work aimed to improve food safety in Benin. In characterizing strains of K. pneumoniae and fluorescent Pseudomonas spp. at the biochemical and molecular level, the target was to identify contaminated watering water and garden products sold during Cotonou in both the dry and rainy seasons. A total of 164 samples of market garden products and 22 samples of watering water were investigated. The results showed that 5.91% of market garden products and watering water were contaminated by K. pneumoniae and 20.43% by fluorescent Pseudomonas spp. During the dry season, cabbage was most contaminated by fluorescent Pseudomonas spp. (50%). Pool water was more contaminated with K. pneumoniae (17%). All isolated strains were resistant to both amoxicillin and penicillin. All strains of K. pneumoniae and fluorescent Pseudomonas spp. were not resistant to imipenem, and 22% of them produced penicillinase. Among the 49 strains producing penicillinase isolated, 64.29% and 21.43% carried blaTEM and blaSHV respectively while 14.28% carried blaCTX-M genes. In light of the previously-developed results and considering the importance of horticultural products in Beninese food habits, we must improve national awareness of the risk for foodborne illness.
Effects of 10 Week Resistance Training and Ginger Consumption on C-reactive protein and Some Cardiovascular Risk Factors in Obese Men

Introduction: The use of exercise along with herbal supplements is one of the recommended methods for controlling obesity and its complications, but its effects have been controversial due to the diversity of training programs and also herbal supplements. Hence, the objective of this study was to investigate the effects of 10 week ginger and progressive resistance training on C-reactive protein (CRP) and other cardiovascular risk factors in obese men. Methods: In a double-blind design, 32 obese men (BMI≥ 30) were selected and randomized to four groups (each group comprised of 8 subjects): 1- ginger (GI) 2- resistance training plus placebo (PLRT) 3- resistance training plus ginger (RTPL) and 4- placebo (PL). Subjects of groups 1 and 3 consumed 1 gr ginger/d for 10 weeks, while subjects of groups 2 and 3 performed progressive resistance training at the same time. To evaluate lipid profiles, insulin resistance and CRP, blood samples were collected at the beginning of the first week and after the last week. Moreover, body composition and anthropometric indices were measured simultaneously. Results: After 10 weeks of interventions, both GRT and PLRT groups showed a significant decrease in WC, WHR, body fat percent, body fat mass, total cholesterol and insulin resistance, while these remained unchanged in two PL and GI groups (P>0.05). Moreover, significant decreases in the mean values of CRP were observed in all groups except the placebo group (P<0.05). Conclusion: According to our results, resistance training was a preventive approach to reduce the cardiovascular risk in obese men. Moreover, ginger supplementation did not have any influence on the lipid profile and insulin resistance at a dose of 1 gr/day, however, it exerted favorable effects on CRP in obese men.
NBER WORKING PAPER SERIES THE IMPACT OF STATE TAX SUBSIDIES FOR PRIVATE LONG-TERM CARE INSURANCE ON COVERAGE AND MEDICAID EXPENDITURES

In spite of the large expected costs of needing long-term care, only 10-12 percent of the elderly population has private insurance coverage. Medicaid, which provides means-tested public assistance and pays for almost half of long-term care costs, spends more than $100 billion annually on long-term care. n this paper, I exploit variation in the adoption and generosity of state tax subsidies for private long-term care insurance to determine whether tax subsidies increase private coverage and reduce Medicaid's costs for long-term care. The results indicate that the average tax subsidy raises coverage rates by 2.7 percentage points, or 28 percent. However, the response is concentrated among high income and asset-rich individuals, populations with low probabilities of relying on Medicaid. Simulations suggest each dollar of state tax expenditure produces approximately $0.84 in Medicaid savings, over half of which funnels to the federal government. Gopi Shah Goda Stanford University SIEPR 366 Galvez St. Stanford, CA 94305 and NBER gopi@stanford.edu
Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.
Structural Basis for Metallic-Like Conductivity in Microbial Nanowires

ABSTRACT Direct measurement of multiple physical properties of Geobacter sulfurreducens pili have demonstrated that they possess metallic-like conductivity, but several studies have suggested that metallic-like conductivity is unlikely based on the structures of the G. sulfurreducens pilus predicted from homology models. In order to further evaluate this discrepancy, pili were examined with synchrotron X-ray microdiffraction and rocking-curve X-ray diffraction. Both techniques revealed a periodic 3.2-Å spacing in conductive, wild-type G. sulfurreducens pili that was missing in the nonconductive pili of strain Aro5, which lack key aromatic acids required for conductivity. The intensity of the 3.2-Å peak increased 100-fold when the pH was shifted from 10.5 to 2, corresponding with a previously reported 100-fold increase in pilus conductivity with this pH change. These results suggest a clear structure-function correlation for metallic-like conductivity that can be attributed to overlapping π-orbitals of aromatic amino acids. A homology model of the G. sulfurreducens pilus was constructed with a Pseudomonas aeruginosa pilus model as a template as an alternative to previous models, which were based on a Neisseria gonorrhoeae pilus structure. This alternative model predicted that aromatic amino acids in G. sulfurreducens pili are packed within 3 to 4 Å, consistent with the experimental results. Thus, the predictions of homology modeling are highly sensitive to assumptions inherent in the model construction. The experimental results reported here further support the concept that the pili of G. sulfurreducens represent a novel class of electronically functional proteins in which aromatic amino acids promote long-distance electron transport. IMPORTANCE The mechanism for long-range electron transport along the conductive pili of Geobacter sulfurreducens is of interest because these “microbial nanowires” are important in biogeochemical cycling as well as applications in bioenergy and bioelectronics. Although proteins are typically insulators, G. sulfurreducens pilus proteins possess metallic-like conductivity. The studies reported here provide important structural insights into the mechanism of the metallic-like conductivity of G. sulfurreducens pili. This information is expected to be useful in the design of novel bioelectronic materials. The mechanism for long-range electron transport along the conductive pili of Geobacter sulfurreducens is of interest because these “microbial nanowires” are important in biogeochemical cycling as well as applications in bioenergy and bioelectronics. Although proteins are typically insulators, G. sulfurreducens pilus proteins possess metallic-like conductivity. The studies reported here provide important structural insights into the mechanism of the metallic-like conductivity of G. sulfurreducens pili. This information is expected to be useful in the design of novel bioelectronic materials.