Miracle-dz/UniFAR-FTUs huggingface dataset:
Vulnerable neuronal subsets in Alzheimer's and Pick's disease are distinguished by their τ isoform distribution and phosphorylation

Aggregated τ proteins constitute the basic matrix of neuronal inclusions specific to numerous neurodegenerative disorders. Monodimensional and two‐dimensional Western blot analyses performed on cortical brain homogenates allowed discrimination between disease‐specific τ protein profiles. These observations raised the issue of the physiopathological significance of such specificities. Alzheimer's disease (AD) pathological τ proteins (PTPs) (τ 74, 69, 55) were compared with those of Pick's disease (PiD) (τ 64, 55) using a panel of antibodies against peptidic sequences of τ isoforms corresponding to exons 2, 3, and 10. AD and PiD could then be critically differentiated by the absence of translated τ isoforms with exon 10 in PiD PTPs, along with the absence of the phosporylation site on Ser262. Immunohistochemical studies corroborate these findings. Indeed, Pick bodies were strongly immunostained by an anti‐“exon 2” antibody but failed to reveal any anti‐exon 10 reactive epitope. Tangles in AD contained exon 2, 3, and 10 epitopes. Altogether, our results demonstrated that Pick bodies develop within specific neuronal subsets that express specific patterns of τ isoforms lacking exon 10 peptidic sequence. We conclude that neurodegenerative disorders imply attrition of selectively vulnerable neuronal subsets, a process revealed, and may be sustained by specific τ isoform patterns.
Erk1/2 MAPK and mTOR signaling sequentially regulates progression through distinct stages of oligodendrocyte differentiation

Myelination is the culmination of a complex process in which oligodendrocyte (OL) progenitors transition through defined stages in a well‐coordinated differentiation program. The signaling mechanisms that regulate this progression are poorly understood. Here we investigate the role of extracellular signal‐regulated‐kinase‐1,‐2 (Erk1/2) and the mammalian target of rapamycin (mTOR), downstream effectors of the Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways, at specific stages of OL development in vitro. Using a panel of developmental stage‐specific antigenic markers and pharmacological inhibitors, we provide evidence that Erk1/2 signaling regulates transition of early progenitors to the late progenitor stage and, as a consequence, to the immature OL stage, but not the transition of immature OL to the mature OL stage. In contrast, mTOR signaling is not required for early progenitor transition to late progenitor stage. Surprisingly, it is also not required for the transition of late progenitors to terminally differentiated immature OLs, as has been reported previously, but is required for the next sequential transition of immature OLs to the mature OL stage. Furthermore, mTOR signaling regulates OL cytoskeletal organization and major myelin protein expression. These in vitro findings correlate with our in vivo data showing that inhibition of mTOR by rapamycin injection attenuated the onset of myelination in the early postnatal brain. Thus, these studies demonstrate that Erk1/2 and mTOR signaling sequentially regulates distinct stages of OL progenitor differentiation and suggest that cells in the OL‐lineage require distinct signaling mechanisms to transition through specific stages of their development. © 2011 Wiley Periodicals, Inc.
Solid propellant launch vehicle development program for Peru

This paper proposes a solid propellant space launch vehicles (SLV) development program considering the indigenous technology development evolution. The proposed program was elaborated with the main objective to deliver a small payload of 100-200 kg into a low earth orbit of 600-800 km altitude. Several LVs have been proposed with specific characteristics and performances, each LV design model has been optimized using a heuristic optimization method. An integrated multidisciplinary design optimization framework based on multi discipline feasible (MDF) has been implemented along with the aerodynamic, propulsion, mass, and dynamic models. The proposed solid propellant SLV development program serves as the basis of future developments and represents a cost effective initiative strategy for a small country with limited space development budget to master the basic knowledge to rapid access into space.
Outlier SNPs show more genetic structure between two Bay of Fundy metapopulations of Atlantic salmon than do neutral SNPs

Atlantic salmon of Eastern Canada were once of considerable importance to aboriginal, recreational, and commercial fisheries, yet many populations are now in decline, particularly those of the inner Bay of Fundy (iBoF), which were recently listed as endangered. We investigated whether nonneutral SNPs could be used to assign individual Atlantic salmon accurately to either the iBoF or the outer Bay of Fundy (oBoF) metapopulations because this has been difficult with existing neutral markers. We first searched for markers under diversifying selection by genotyping eight captively bred Bay of Fundy (BoF) populations for 320 SNP loci with the Sequenom MassARRAY™ system and then analysed the data set with four different FST outlier detection programs. Three outlier loci were identified by both BayesFST and BayeScan whereas seven outlier loci, including the three previously mentioned, were identified by both Fdist and Arlequin. A subset of 14 nonneutral SNPs was more accurate (85% accuracy) than a subset of 67 neutral SNPs (75% accuracy) at assigning individual salmon back to their metapopulation. We then chose a subset of nine outlier SNP markers and used them to inexpensively genotype archived DNA samples from seven wild BoF populations using Invader™ chemistry. Hierarchical AMOVA of these independent wild samples corroborated our previous findings of significant genetic differentiation between iBoF and oBoF salmon metapopulations. Our research shows that identifying and using outlier loci is an important step towards achieving the goal of consistently and accurately distinguishing iBoF from oBoF Atlantic salmon, which will aid in their conservation.
Activation of Stress-activated Protein Kinase/c-Jun NH2-terminal Kinase and p38 Kinase in Calphostin C-induced Apoptosis Requires Caspase-3-like Proteases but Is Dispensable for Cell Death*

Apoptosis was induced in human glioma cell lines by exposure to 100 nm calphostin C, a specific inhibitor of protein kinase C. Calphostin C-induced apoptosis was associated with synchronous down-regulation of Bcl-2 and Bcl-xL as well as activation of caspase-3 but not caspase-1. The exposure to calphostin C led to activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) and p38 kinase and concurrent inhibition of extracellular signal-regulated kinase (ERK). Upstream of ERK, Shc was shown to be activated, but its downstream Raf1 and ERK were inhibited. The pretreatment with acetyl-Tyr-Val-Ala-Asp-aldehyde, a relatively selective inhibitor of caspase-3, or benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD.fmk), a broad spectrum caspase inhibitor, similarly inhibited calphostin C-induced activation of SAPK/JNK and p38 kinase as well as apoptotic nuclear damages (chromatin condensation and DNA fragmentation) and cell shrinkage, suggesting that caspase-3 functions upstream of SAPK/JNK and p38 kinase, but did not block calphostin C-induced surface blebbing and cell death. On the other hand, the inhibition of SAPK/JNK by transfection of dominant negative SAPK/JNK and that of p38 kinase by SB203580 induced similar effects on the calphostin C-induced apoptotic phenotypes and cell death as did z-VAD.fmk and acetyl-Tyr-Val-Ala-Asp-aldehyde, but the calphostin C-induced PARP cleavage was not changed, suggesting that SAPK/JNK and p38 kinase are involved in the DNA fragmentation pathway downstream of caspase-3. The present findings suggest, therefore, that the activation of SAPK/JNK and p38 kinase is dispensable for calphostin C-mediated and z-VAD.fmk-resistant cell death.
Access to productive assets and impact on household welfare in rural Uganda

This article estimates the poverty reducing impact of land access in rural Uganda. Using balanced panel data for 309 households in 2001, 2003, and 2005, models that control for unobserved household heterogeneity and endogeneity of land acquisition and disposition are employed to measure the poverty-reduction effect of land on household expenditure per adult equivalent. Significant poverty reduction effects of increased land access in form of owned, operated and market-accessed land were found. The poverty reduction effect for land accessed through the market was significantly larger than the poverty reduction effect of land accessed through inheritance. (JEL Q24, Q15, and O12)
Transmissibility and geographic spread of the 1889 influenza pandemic

Until now, mortality and spreading mechanisms of influenza pandemics have been studied only for the 1918, 1957, and 1968 pandemics; none have concerned the 19th century. Herein, we examined the 1889 “Russian” pandemic. Clinical attack rates were retrieved for 408 geographic entities in 14 European countries and in the United States. Case fatality ratios were estimated from datasets in the French, British and German armies, and morbidity and mortality records of Swiss cities. Weekly all-cause mortality was analyzed in 96 European and American cities. The pandemic spread rapidly, taking only 4 months to circumnavigate the planet, peaking in the United States 70 days after the original peak in St. Petersburg. The median and interquartile range of clinical attack rates was 60% (45–70%). The case fatality ratios ranged from 0.1% to 0.28%, which is comparable to those of 1957 and 1968, and 10-fold lower than in 1918. The median basic reproduction number (R0 ) was 2.1, which is comparable to the values found for the other pandemics, despite the different viruses and contact networks. R0 values varied widely from one city to another, and only a small minority of those values was within the range in which modelers’ mitigation scenarios predicted effectiveness. The 1889 and 1918 R0 correlated for the subset of cities for which both values were available. Social and geographic factors probably shape the local R0 , and they could be identified to design optimal mitigation scenarios tailored to each city.
Adoption of System of Rice Intensification under Information Constraints: An Analysis for India

Abstract This study examines the role of information constraints in the adoption of the System of Rice Intensification (SRI) in India by explicitly incorporating information in the adoption model. The results showed that effective information along with other factors such as membership in a farmer organisation, availability of labourers, irrigation facility and so forth were important in determining the SRI adoption. The results also revealed that the Government of India’s National Food Security Mission programme did not have significant impact in promoting greater dissemination and adoption of SRI.
The incidence and nature of prescribing and medication administration errors in paediatric inpatients

Objectives To determine the incidence and nature of prescribing and medication administration errors in paediatric inpatients. Design Prospective review of drug charts to identify prescribing errors and prospective observation of nurses preparing and administering drugs to identify medication administration errors. In addition, incident reports were collected for each ward studied. Participants Paediatric patients admitted to hospitals and nurses administering medications to these patients. Setting 11 wards (prescribing errors) and 10 wards (medication administration errors) across five hospitals (one specialist children’s teaching hospital, one nonteaching hospital and three teaching hospitals) in the London area (UK). Main outcome measures Number, types and incidence of prescribing and medication administration errors, using practitioner-based definitions. Results 391 prescribing errors were identified, giving an overall prescribing error rate of 13.2% of medication orders (95% CI 12.0 to 14.5). There was great variation in prescribing error rates between wards. Incomplete prescriptions were the most common type of prescribing error, and dosing errors the third most common. 429 medication administration errors were identified; giving an overall incidence of 19.1% (95% CI 17.5% to 20.7%) erroneous administrations. Errors in drug preparation were the most common, followed by incorrect rates of intravenous administration. Conclusions Prescribing and medication administration errors are not uncommon in paediatrics, partly as a result of the extra challenges in prescribing and administering medication to this patient group. The causes and extent of these errors need to be explored locally and improvement strategies pursued.
Semantic Clustering Using Multiple Ontologies

Data mining tools able to semantically interpret textual or linguistic data are acquiring a growing importance. Moreover, the development of large ontologies for general and specific domains provides new tools to include background knowledge into data mining techniques such as clustering. In this paper we present an unsupervised clustering method that exploits the semantics of categorical data by means of ontologies, and it is also able to manage numerical data. Our method is able to use different ontologies in order to assess the meaning of the values during the clustering process, leading to a set of clusters with a clearer semantic interpretation in a particular domain. The influence of using one or several ontologies is analyzed by using real data collected from visitors to the Ebre Delta Natural Park, which is a protected natural reserve in Catalonia (Spain).
Alteration of Frizzled Expression in Renal Cell Carcinoma

To evaluate the involvement of frizzled receptors (Fzds) in oncogenesis, we investigated mRNA expression levels of several human Fzds in more than 30 different human tumor samples and their corresponding (matched) normal tissue samples, using real-time quantitative PCR. We observed that the mRNA level of Fzd5 was markedly increased in 8 of 11 renal carcinoma samples whilst Fzd8 mRNA was increased in 7 of 11 renal carcinoma samples. Western blot analysis of crude membrane fractions revealed that Fzd5 protein expression in the matched tumor/normal kidney samples correlated with the observed mRNA level. Wnt/β-catenin signaling pathway activation was confirmed by the increased expression of a set of target genes. Using a kidney tumor tissue array, Fzd5 protein expression was investigated in a broader panel of kidney tumor samples. Fzd5 membrane staining was detected in 30% of clear cell carcinomas, and there was a strong correlation with nuclear cyclin D1 staining in the samples. Our data suggested that altered expression of certain members of the Fzd family, and their downstream targets, could provide alternative mechanisms leading to activation of the Wnt signaling pathway in renal carcinogenesis. Fzd family members may have a role as a biomarker.
Tocopherols Protect Synechocystis sp. Strain PCC 6803 from Lipid Peroxidation1

Tocopherols (vitamin E) are lipid-soluble antioxidants synthesized only by photosynthetic eukaryotes and some cyanobacteria, and have been assumed to play important roles in protecting photosynthetic membranes from oxidative stress. To test this hypothesis, tocopherol-deficient mutants of Synechocystis sp. strain PCC 6803 (slr1736 and slr1737 mutants) were challenged with a series of reactive oxygen species-generating and lipid peroxidation-inducing chemicals in combination with high-light (HL) intensity stress. The tocopherol-deficient mutants and wild type were indistinguishable in their growth responses to HL in the presence and absence of superoxide and singlet oxygen-generating chemicals. However, the mutants showed enhanced sensitivity to linoleic or linolenic acid treatments in combination with HL, consistent with tocopherols playing a crucial role in protecting Synechocystis sp. strain PCC 6803 cells from lipid peroxidation. The tocopherol-deficient mutants were also more susceptible to HL treatment in the presence of sublethal levels of norflurazon, an inhibitor of carotenoid synthesis, suggesting carotenoids and tocopherols functionally interact or have complementary or overlapping roles in protecting Synechocystis sp. strain PCC 6803 from lipid peroxidation and HL stress.
FASTER LIZARDS SIRE MORE OFFSPRING: SEXUAL SELECTION ON WHOLE‐ANIMAL PERFORMANCE

Abstract Sexual selection operates by acting on variation in mating success. However, since selection acts on whole‐organism manifestations (i.e., performance) of underlying morphological traits, tests for phenotypic effects of sexual selection should consider whole‐animal performance as a substrate for sexual selection. Previous studies have revealed positive relationships between performance and survival, that is, natural selection, but none have explicitly tested whether performance may influence reproductive success (through more matings), that is, sexual selection. Performance predicts dominance in some species, implying the effects of sexual selection, but how it does so has not been established, nor is it certain whether performance might be a by‐product of selection for something else, for example, elevated circulating testosterone levels. We investigated the potential for sexual selection on sprint speed performance in collared lizards (Crotaphytus collaris), considering the potential mediating effects of circulating hormone levels. Among territorial, adult male collared lizards, only sprint speed significantly predicted territory area and number of offspring sired as determined by genetic paternity analysis. Body size, head size, and hind limb length had no effect. Neither plasma testosterone levels nor corticosterone levels correlated with sprint speed, territory area, or number of offspring sired. Thus, our results provide a direct link between whole‐animal performance and reproductive success, suggesting that intrasexual selection can act directly on sprint speed performance and drive the evolution of underlying morphological traits.
LPV system identification using the matchable observable linear identification approach

This article presents an optimal estimator for discrete-time systems disturbed by output white noise, where the proposed algorithm identifies the parameters of a Multiple Input Single Output LPV State Space model. This is an LPV version of a class of algorithms proposed elsewhere for identifying LTI systems. These algorithms use the matchable observable linear identification parameterization that leads to an LTI predictor in a linear regression form, where the ouput prediction is a linear function of the unknown parameters. With a proper choice of the predictor parameters, the optimal prediction error estimator can be approximated. In a previous work, an LPV version of this method, that also used an LTI predictor, was proposed; this LTI predictor was in a linear regression form enablin, in this way, the model estimation to be handled by a Least-Squares Support Vector Machine approach, where the kernel functions had to be filtered by an LTI 2D-system with the predictor dynamics. As a result, it can never approximate an optimal LPV predictor which is essential for an optimal prediction error LPV estimator. In this work, both the unknown parameters and the state-matrix of the output predictor are described as a linear combination of a finite number of basis functions of the scheduling signal; the LPV predictor is derived and it is shown to be also in the regression form, allowing the unknown parameters to be estimated by a simple linear least squares method. Due to the LPV nature of the predictor, a proper choice of its parameters can lead to the formulation of an optimal prediction error LPV estimator. Simulated examples are used to assess the effectiveness of the algorithm. In future work, optimal prediction error estimators will be derived for more general disturbances and the LPV predictor will be used in the Least-Squares Support Vector Machine approach.
A Goal-Directed Visual Perception System Using Object-Based Top–Down Attention

The selective attention mechanism is employed by humans and primates to realize a truly intelligent perception system, which has the cognitive capability of learning and thinking about how to perceive the environment autonomously. The attention mechanism involves the top-down and bottom-up ways that correspond to the goal-directed and automatic perceptual behaviors, respectively. Rather than considering the automatic perception, this paper presents an artificial system of the goal-directed visual perception by using the object-based top-down visual attention mechanism. This cognitive system can guide the perception to an object of interest according to the current task, context and learned knowledge. It consists of three successive stages: preattentive processing, top-down attentional selection and post-attentive perception. The preattentive processing stage divides the input scene into homogeneous proto-objects, one of which is then selected by the top-down attention and finally sent to the post-attentive perception stage for high-level analysis. Experimental results of target detection in the cluttered environments are shown to validate this system.
Task Replication for Deadline-Constrained Vehicular Cloud Computing: Optimal Policy, Performance Analysis, and Implications on Road Traffic

In vehicular cloud computing (VCC) systems, the computational resources of moving vehicles are exploited and managed by infrastructures, e.g., roadside units, to provide computational services. The offloading of computational tasks and collection of results rely on successful transmissions between vehicles and infrastructures during encounters. In this paper, we investigate how to provide timely computational services in VCC systems. In particular, we seek to minimize the deadline violation probability given a set of tasks to be executed in vehicular clouds. Due to the uncertainty of vehicle movements, the task replication methodology is leveraged which allows one task to be executed by several vehicles, and thus trading computational resources for delay reduction. The optimal task replication policy is of key interest. We first formulate the problem as a finite-horizon sampled-time Markov decision problem and obtain the optimal policy by value iterations. To conquer the complexity issue, we propose the balanced-task-assignment (BETA) policy which is proved optimal and has a clear structure: it always assigns the task with the minimum number of replicas. Moreover, a tight closed-form performance upper bound for the BETA policy is derived, which indicates that the deadline violation probability follows the Rayleigh distribution approximately. Applying the vehicle speed-density relationship in the traffic flow theory, we find that vehicle mobility benefits VCC systems more compared with road traffic systems, by showing that the optimum vehicle speed to minimize the deadline violation probability is larger than the critical vehicle speed in traffic theory which maximizes traffic flow efficiency.