Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards Kinetic Modeling of Global Metabolic Networks with Incomplete Experimental Input on Kinetic Parameters

This is the first report, to our knowledge, on a systematic method for constructing a large scale kinetic metabolic model with incomplete information on kinetic parametersr, and its initial application to the modeling of central metabolism of Methylobacterium extorquens AM1, a methylotrophic and environmental important bacterium, with all necessary constraints. Through a systematic and consistent procedure of finding a set of parameters in the physiological range we overcome an outstanding difficulty in large scale kinetic modeling: the requirement for a massive number of enzymatic reaction parameters. We are able to construct the kinetic model based on general biological considerations and incomplete experimental kinetic parameters. The success of our approach with incompletely input information is guaranteed by two known principles in biology, the robustness of the system and the cooperation among its various parts. (Will be pleased to be informed on other methodologies dealing with same type of problems: aoping@u.washington.edu)
Preview : Published ahead of advance online publication Upregulation of Inflammasome activity and increased gut permeability are associated with obesity in children and adolescents

This is a PDF file of an unedited peer-reviewed manuscript that has been accepted for publication. NPG are providing this early version of the manuscript as a service to our customers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.
Sequence Analysis of the msp4 Gene of Anaplasma phagocytophilum Strains

ABSTRACT The causative agent of human granulocytic ehrlichiosis was recently reclassified as Anaplasma phagocytophilum, unifying previously described bacteria that cause disease in humans, horses, dogs, and ruminants. For the characterization of genetic heterogeneity in this species, the homologue of Anaplasma marginale major surface protein 4 gene (msp4) was identified, and the coding region was PCR amplified and sequenced from a variety of sources, including 50 samples from the United States, Germany, Poland, Norway, Italy, and Switzerland and 4 samples of A. phagocytophilum-like organisms obtained from white-tailed deer in the United States. Sequence variation between strains of A. phagocytophilum (90 to 100% identity at the nucleotide level and 92 to 100% similarity at the protein level) was higher than in A. marginale. Phylogenetic analyses of msp4 sequences did not provide phylogeographic information but did differentiate strains of A. phagocytophilum obtained from ruminants from those obtained from humans, dogs, and horses. The sequence analysis of the recently discovered A. phagocytophilum msp2 gene corroborated these results. The results reported here suggest that although A. phagocytophilum-like organisms from white-tailed deer may be closely related to A. phagocytophilum, they could be more diverse. These results suggest that A. phagocytophilum strains from ruminants could share some common characteristics, including reservoirs and pathogenicity, which may be different from strains that infect humans.
Absence of inducible nitric oxide synthase modulates early reperfusion‐induced NF‐κB and AP‐1 activation and enhances myocardial damage

The role of nitric oxide (NO) generated by the inducible NO synthase (iNOS) during myocardial ischemia and reperfusion is not understood. We investigated the role of iNOS during early reperfusion damage induced in genetically deficient iNOS (iNOS‐/‐) mice and wild‐type littermates. In wild‐type mice, ischemia (60 min) and reperfusion (60 min) induced an elevation in serum levels of creatine phosphokinase and myocardial injury characterized by the presence of scattered apoptotic myocytes and mild neutrophil infiltration. Northern blot analysis showed increased expression of iNOS, whose activity was markedly elevated after reperfusion. Immunohistochemistry showed staining for nitrotyrosine; Western blot analysis showed elevated expression of heat shock protein 70 (HSP70), a putative cardioprotective mediator. Plasma levels of nitrite and nitrate, tumor necrosis factor α (TNF‐α), interleukin 6 (IL‐6), and IL‐10 were also increased. These events were preceded by degradation of inhibitor κBα (IκBα), activation of IκB kinase complex (IKK) and c‐Jun‐NH2‐terminal kinase (JNK), and subsequently activation of nuclear factor‐κB (NF‐κB) and activator protein 1 (AP‐1) as early as 15 min after reperfusion. In contrast, iNOS‐/‐ mice experienced 35% mortality after reperfusion. The extensive myocardial injury was associated with marked apoptosis and infiltration of neutrophils whereas expression of HSP70 was less pronounced. Nitrotyrosine formation and plasma levels of nitrite and nitrate were undetectable. TNF‐α and IL‐6 were increased and IL‐10 was reduced in earlier stages of reperfusion. Activation of IKK and JNK and binding activity of NF‐κB and AP‐1 were significantly reduced. Thus, we conclude that iNOS plays a beneficial role in modulating the early defensive inflammatory response against reperfusion injury through regulation of signal transduction. —Zingarelli, B. , Hake, P. W. , Yang, Z. , O’Connor, M. , Denenberg, A. , Wong, H. R. Absence of inducible nitric oxide synthase modulates early reperfusion‐induced NF‐κB and AP‐1 activation and enhances myocardial damage. FASEB J. 16, 327–342 (2002)
The Impact of Customer-Based Brand Equity on Revisit Intentions: An Empirical Study of Business and Leisure Travelers at Five Shanghai Budget Hotels

The purpose of this study is to explore how, from a customers’ point of view, brand equity influences budget hotel revisit intentions. The research is based on a convenience sample of 400 respondents who had stayed at top-5 budget hotels in Shanghai, China, from July 10 to July 20, 2010. The results show that, in sequence of degree of significance, brand loyalty, brand awareness/brand association and perceived quality as brand equity sub-dimensions have positive relationships with perceived value and revisit intentions. Additionally perceived value plays an increasingly important role in budget hotel revisit intentions. It was also discovered that the effect of brand loyalty on revisit intention is greater for business travelers than for leisure ones. There is also no difference between business and leisure travelers in terms of their respective impact on brand awareness/brand association, perceived quality, and perceived value on revisit intentions.
APDB: a novel measure for benchmarking sequence alignment methods without reference alignments

MOTIVATION We describe APDB, a novel measure for evaluating the quality of a protein sequence alignment, given two or more PDB structures. This evaluation does not require a reference alignment or a structure superposition. APDB is designed to efficiently and objectively benchmark multiple sequence alignment methods. RESULTS Using existing collections of reference multiple sequence alignments and existing alignment methods, we show that APDB gives results that are consistent with those obtained using conventional evaluations. We also show that APDB is suitable for evaluating sequence alignments that are structurally equivalent. We conclude that APDB provides an alternative to more conventional methods used for benchmarking sequence alignment packages.
Parameters affecting the early seedling development of four neotropical trees under oxygen deprivation stress.

Some of the parameters that determine flooding resistance-and consequently habitat zonation-were investigated in four neotropical trees (Schizolobium parahyba, Sebastiania commersoniana, Erythrina speciosa and Sesbania virgata). The constitutive parameters of seeds (size, nature and amount of reserves) only partly influenced resistance to flooding, mainly through a high carbohydrate : size ratio. Parameters describing metabolic efficiency under stress conditions were more important. Among them, fermentation capacity and levels of ATP and of total adenylates played a key role. The highest resistance to anoxia was associated with increased availability of free sugars, elevated alcohol dehydrogenase activity and corresponding mRNA levels, more efficient removal of ethanol and lactate, and higher adenylate levels. Finally, as a lethal consequence of energy shortage, free fatty acids were released on a massive scale in the flooding-sensitive species Schizolobium parahyba, whereas lipid hydrolysis did not occur in the most resistant species Sesbania virgata.
Experimental meandering river with chute cutoffs

[1] Braided rivers are relatively simple to produce in the laboratory, whereas dynamic meandering rivers have not been sustained beyond initial bend formation. Meandering is theoretically explained by bend instability growing from planimetric perturbation, which convects downstream. In this study, we experimentally tested the importance of upstream perturbation and chute cutoff development in the evolution and dynamics of a meandering channel pattern. The initial straight channel had a transversely moving upstream inlet point and silt-sized silica flour was added to the sediment feed to allow floodplain formation. We obtained a dynamic meandering river with scroll bars. Bend growth was alternated by chute cutoffs that formed across the point bars. Meandering was maintained as one channel was disconnected by a plug bar. The curvature at the chute bifurcation transported sediment and build a new floodplain, while the other channel widens. At the end of the experiment, the fluvial plain exhibited a meandering channel, point bars, chutes and abandoned and partially filled channels with a slightly cohesive floodplain surface similar to natural meandering gravel bed rivers. We conclude that the necessary and sufficient conditions for dynamic meandering gravel bed river are a sustained dynamic upstream perturbation and floodplain formation.
CherryPick: Adaptively Unearthing the Best Cloud Configurations for Big Data Analytics

Picking the right cloud configuration for recurring big data analytics jobs running in clouds is hard, because there can be tens of possible VM instance types and even more cluster sizes to pick from. Choosing poorly can significantly degrade performance and increase the cost to run a job by 2-3x on average, and as much as 12x in the worst-case. However, it is challenging to automatically identify the best configuration for a broad spectrum of applications and cloud configurations with low search cost. CherryPick is a system that leverages Bayesian Optimization to build performance models for various applications, and the models are just accurate enough to distinguish the best or close-to-the-best configuration from the rest with only a few test runs. Our experiments on five analytic applications in AWS EC2 show that CherryPick has a 45-90% chance to find optimal configurations, otherwise near-optimal, saving up to 75% search cost compared to existing solutions.
Newcastle University E-prints Citation for Item: P53, Skp2, and Dkk3 as Mycn Target Genes and Their Potential Therapeutic Significance

Always use the definitive version when citing. The full-text may be used and/or reproduced and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not for profit purposes provided that:  A full bibliographic reference is made to the original source  A link is made to the metadata record in Newcastle E-prints  The full text is not changed in any way. The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Neuroblastoma is the most common extra-cranial solid tumor of childhood. Despite significant advances, it currently still remains one of the most difficult childhood cancers to cure, with less than 40% of patients with high-risk disease being long-term survivors. MYCN is a proto-oncogene implicated to be directly involved in neuroblastoma development. Amplification of MYCN is associated with rapid tumor progression and poor prognosis. Novel therapeutic strategies which can improve the survival rates whilst reducing the toxicity in these patients are therefore required. Here we discuss genes regulated by MYCN in neuroblastoma, with particular reference to p53, SKP2, and DKK3 and strategies that may be employed to target them.
Shady paths: leveraging surfing crowds to detect malicious web pages

The web is one of the most popular vectors to spread malware. Attackers lure victims to visit compromised web pages or entice them to click on malicious links. These victims are redirected to sites that exploit their browsers or trick them into installing malicious software using social engineering. In this paper, we tackle the problem of detecting malicious web pages from a novel angle. Instead of looking at particular features of a (malicious) web page, we analyze how a large and diverse set of web browsers reach these pages. That is, we use the browsers of a collection of web users to record their interactions with websites, as well as the redirections they go through to reach their final destinations. We then aggregate the different redirection chains that lead to a specific web page and analyze the characteristics of the resulting redirection graph. As we will show, these characteristics can be used to detect malicious pages. We argue that our approach is less prone to evasion than previous systems, allows us to also detect scam pages that rely on social engineering rather than only those that exploit browser vulnerabilities, and can be implemented efficiently. We developed a system, called SpiderWeb, which implements our proposed approach. We show that this system works well in detecting web pages that deliver malware.
Congenital cytomegalovirus infection – a common cause of hearing loss of unknown aetiology

Aim: The aim of this study was to investigate the role of congenital cytomegalovirus (CMV) infection as a cause of various types of sensorineural hearing loss (SNHL) in a group of nonsyndromic children with otherwise unknown aetiology of hearing loss. Furthermore, the occurrence of combined congenital CMV infection and connexin 26 (Cx26) mutations was investigated.
Impact of signaling microcompartment geometry on GPCR dynamics in live retinal photoreceptors

G protein–coupled receptor (GPCR) cascades rely on membrane protein diffusion for signaling and are generally found in spatially constrained subcellular microcompartments. How the geometry of these microcompartments impacts cascade activities, however, is not understood, primarily because of the inability of current live cell–imaging technologies to resolve these small structures. Here, we examine the dynamics of the GPCR rhodopsin within discrete signaling microcompartments of live photoreceptors using a novel high resolution approach. Rhodopsin fused to green fluorescent protein variants, either enhanced green fluorescent protein (EGFP) or the photoactivatable PAGFP (Rho-E/PAGFP), was expressed transgenically in Xenopus laevis rod photoreceptors, and the geometries of light signaling microcompartments formed by lamellar disc membranes and their incisure clefts were resolved by confocal imaging. Multiphoton fluorescence relaxation after photoconversion experiments were then performed with a Ti–sapphire laser focused to the diffraction limit, which produced small sub–cubic micrometer volumes of photoconverted molecules within the discrete microcompartments. A model of molecular diffusion was developed that allows the geometry of the particular compartment being examined to be specified. This was used to interpret the experimental results. Using this unique approach, we showed that rhodopsin mobility across the disc surface was highly heterogeneous. The overall relaxation of Rho-PAGFP fluorescence photoactivated within a microcompartment was biphasic, with a fast phase lasting several seconds and a slow phase of variable duration that required up to several minutes to reach equilibrium. Local Rho-EGFP diffusion within defined compartments was monotonic, however, with an effective lateral diffusion coefficient Dlat = 0.130 ± 0.012 µm2s−1. Comparison of rhodopsin-PAGFP relaxation time courses with model predictions revealed that microcompartment geometry alone may explain both fast local rhodopsin diffusion and its slow equilibration across the greater disc membrane. Our approach has for the first time allowed direct examination of GPCR dynamics within a live cell signaling microcompartment and a quantitative assessment of the impact of compartment geometry on GPCR activity.
Connectional and Architectonic Evidence for Dorsal and Ventral V3, and Dorsomedial Area in Marmoset Monkeys

The existence of a third visual area, V3, along the outer margin of V2 was originally proposed for primates on the basis of projections from V1. The evidence for V3 was never totally convincing because investigators failed to demonstrate V1 projections to ventral V3, and projections to dorsal V3 could be attributed to the dorsomedial visual area (DM). We have reexamined the issue by placing large injections into both dorsal and ventral portions of V1 and subsequently processing flattened cortex for myelin and cytochrome oxidase so that borders of V1 and V2 could be determined accurately. The injections were in small-brained marmosets, where ventral V1 was most accessible and cortex could be flattened easily. The results indicate that dorsal V1 (representing the lower visual quadrant) projects to a narrow “dorsal V3” located between DM and dorsal V2, whereas ventral V1 (representing the upper visual quadrant) projects to a narrow “ventral V3. ” Architectonic borders for these dorsal and ventral strips were clearly apparent. In addition, all parts of V1 project to DM, whereas ventral V1 connections indicate that the dorsolateral area (DL) extends more ventral than has been established previously. We also placed injections within dorsal V2, dorsal and ventral DM, and dorsal, central, and ventral middle temporal (MT) area. Results from these injections were consistent with the proposed retinotopic organizations of V3, DM, and DL. We provide compelling evidence for the existence of areas V3, DM, and DL in marmosets and suggest that these areas are likely to be found in all primates.
Decoding Visual Location From Neural Patterns in the Auditory Cortex of the Congenitally Deaf

Sensory cortices of individuals who are congenitally deprived of a sense can exhibit considerable plasticity and be recruited to process information from the senses that remain intact. Here, we explored whether the auditory cortex of congenitally deaf individuals represents visual field location of a stimulus—a dimension that is represented in early visual areas. We used functional MRI to measure neural activity in auditory and visual cortices of congenitally deaf and hearing humans while they observed stimuli typically used for mapping visual field preferences in visual cortex. We found that the location of a visual stimulus can be successfully decoded from the patterns of neural activity in auditory cortex of congenitally deaf but not hearing individuals. This is particularly true for locations within the horizontal plane and within peripheral vision. These data show that the representations stored within neuroplastically changed auditory cortex can align with dimensions that are typically represented in visual cortex.
Effects of Absorption with Pneumococcal Type 22F Polysaccharide on Maternal, Cord Blood, and Infant Immunoglobulin G Antipneumococcal Polysaccharide Antibodies

ABSTRACT The aim of this study was to evaluate the effect of absorption with pneumococcal type 22F polysaccharide on antipneumococcal antibody titers in unimmunized Chilean pregnant women and on antibodies in their offspring at birth and 3, 6, and 12 months of age. Sera from 10 healthy pregnant women and from their offspring at birth and at 3, 6, and 12 months of age were studied. Immunoglobulin G antibodies against serotypes 1, 3, 4, 5, 6B, 9V, 14, 18, 19F, and 23F were measured by a standardized enzyme-linked immunosorbent assay method. All sera were absorbed with polysaccharide C, and aliquots of each serum were absorbed with polysaccharide 22F. Individual results were expressed in μg/ml based on the standard serum pool 89-SF. Absorption with polysaccharide 22F reduced antibody concentrations in all samples and to all 10 serotypes studied. Reduction was highest in maternal sera and in cord blood, but it was also present at 3, 6, and 12 months of age. The percent reduction ranged from 24% for serotype 14 to 50% for serotype 1 in maternal samples and from 20% for serotype 18C to 49% for serotype 4 in cord blood samples. The percentages of transplacental transmission were similar for nonabsorbed and absorbed maternal fetal pairs. Absorption with serotype 22F had a significant impact on antipneumococcal antibody concentrations in unimmunized pregnant women and in their offspring. Our results suggest that absorption with 22F polysaccharide needs to be performed in studies of transplacental transmission of antipneumococcal antibodies.
Beyond the dopamine receptor: novel therapeutic targets for treating schizophrenia

All current drugs approved to treat schizophrenia appear to exert their antipsychotic effects through blocking the dopamine D2 receptor. Recent meta-analyses and comparative efficacy studies indicate marginal differences in efficacy of newer atypical antipsychotics and the older drugs, and little effects on negative and cognitive symptoms. This review integrates findings from postmortem, imaging, and drug-challenge studies to elucidate a corticolimbic “pathologic circuit” in schizophrenia that may be particularly relevant to the negative symptoms and cognitive impairments of schizophrenia. Potential sites for pharmacologic intervention targeting glutatatergic, GABAergic, and cholinergic neurotransmission to treat these symptoms of schizophrenia are discussed.
The Inconsistency in Gödel's Ontological Argument: A Success Story for AI in Metaphysics

This paper discusses the discovery of the inconsistency in Godel's ontological argument as a success story for artificial intelligence. Despite the popularity of the argument since the appearance of Godel's manuscript in the early 1970's, the inconsistency of the axioms used in the argument remained unnoticed until 2013, when it was detected automatically by the higher-order theorem prover LEO-II. Understanding and verifying the refutation generated by the prover turned out to be a time-consuming task. Its completion, as reported here, required the reconstruction of the refutation in the Isabelle proof assistant, and it also led to a novel and more efficient way of automating higher-order modal logic S5 with a universal accessibility relation. Furthermore, the development of an improved syntactical hiding for the utilized logic embedding technique allows the refutation to be presented in a human-friendly way, suitable for non-experts in the technicalities of higher-order theorem proving. This brings us a step closer to wider adoption of logic-based artificial intelligence tools by philosophers.
Dynamic mechanical properties of bone cements

Abstract: Polymeric bone cements are viscoelastic materials. Dynamic mechanical analysis (DMA) is a powerful technique for the characterisation of polymers. Viscoelastic parameters of storage and loss moduli, mechanical loss factors (tan δ ) as well as important thermal transition temperature and polymer relaxation processes are easily quantified as a function of temperature and frequency. This chapter explores the viscoelasticity of polymers, DMA as a characterisation tool and the use of DMA in the characterisation of polymeric bone cements.