Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of TLS DNA polymerases eta and kappa in processing naturally occurring structured DNA in human cells

Accurate DNA replication during S‐phase is fundamental to maintain genome integrity. During this critical process, replication forks frequently encounter obstacles that impede their progression. While the regulatory pathways which act in response to exogenous replication stress are beginning to emerge, the mechanisms by which fork integrity is maintained at naturally occurring endogenous replication‐impeding sequences remains obscure. Notably, little is known about how cells replicate through special chromosomal regions containing structured non‐B DNA, for example, G4 quartets, known to hamper fork progression or trigger chromosomal rearrangements. Here, we have investigated the role in this process of the human translesion synthesis (TLS) DNA polymerases of the Y‐family (pol η, pol ι, and pol κ), specialized enzymes known to synthesize DNA through DNA damage. We show that depletion by RNA interference of expression of the genes for Pol η or Pol κ, but not Pol ι, sensitizes U2OS cells treated with the G4‐tetraplex interactive compound telomestatin and triggers double‐strand breaks in HeLa cells harboring multiple copies of a G‐rich sequence from the promoter region of the human c‐MYC gene, chromosomally integrated as a transgene. Moreover, we found that downregulation of Pol κ only raises the level of DSB in HeLa cells containing either one of two breakage hotspot structured DNA sequences in the chromosome, the major break region (Mbr) of BCL‐2 gene and the GA rich region from the far right‐hand end of the genome of the Kaposi Sarcoma associated Herpesvirus. These data suggest that naturally occurring DNA structures are physiological substrates of both pol η and pol κ. We discuss these data in the light of their downregulation in human cancers. © 2008 Wiley‐Liss, Inc.
Protein model quality assessment prediction by combining fragment comparisons and a consensus Cα contact potential

In this work, we develop a fully automated method for the quality assessment prediction of protein structural models generated by structure prediction approaches such as fold recognition servers, or ab initio methods. The approach is based on fragment comparisons and a consensus Cα contact potential derived from the set of models to be assessed and was tested on CASP7 server models. The average Pearson linear correlation coefficient between predicted quality and model GDT‐score per target is 0.83 for the 98 targets, which is better than those of other quality assessment methods that participated in CASP7. Our method also outperforms the other methods by about 3% as assessed by the total GDT‐score of the selected top models. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Novel biomarkers of atherosclerosis and cardiovascular risk in autoimmune diseases: Genomics and proteomics approaches

Atherosclerosis (AT) and cardiovascular disease (CVD) are enhanced in autoimmune diseases such as antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). The reason for this accelerated process is still debatable and, although traditional risk factors are more prevalent in those patients than in general population, they do not fully explain that enhanced risk. Inflammatory components of the immune response, mainly interleukins, TNF‐α, and IFN‐γ, as well as some autoantibodies, including anti‐oxidized low density lipoproteins (anti‐oxLDL), anti‐beta‐2‐Glycoprotein 1 (anti‐ β2GPI), anti‐Heat shock proteins 60/65 (anti‐HSP60/65), and anti‐oxLDL/β2GPI have been shown to play a leading role in the pathogenesis of both, AT and CVD. However, the role of the autoantibodies in accelerated AT in autoimmune disease patients is still controversial. Recently, DNA microarray and proteomic‐based approaches have made substantial breakthrough into the study of various rheumatic diseases, thus allowing for the discovery of previously unknown proteins involved in CVD including some that may be suitable to be used as biomarkers. Herein, we review recent genomics and proteomic approaches that have been applied to the study of autoimmune diseases with atherosclerotic and CV risk. The pharmacogenomics and pharmacoproteomics studies given over to the analysis of ancient and new drugs used to relieve the physiopathology associated to these complex diseases are also discussed.
Cholesterol‐loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7‐NPs‐Chol), which per se is not blood–brain barrier (BBB) permeable, to obtain high‐rate cholesterol delivery into the brain after intraperitoneal injection in HD mice. We report that g7‐NPs, in contrast to unmodified NPs, efficiently crossed the BBB and localized in glial and neuronal cells in different brain regions. We also found that repeated systemic delivery of g7‐NPs‐Chol rescued synaptic and cognitive dysfunction and partially improved global activity in HD mice. These results demonstrate that cholesterol supplementation to the HD brain reverses functional alterations associated with HD and highlight the potential of this new drug‐administration route to the diseased brain.
A wavelet-based technique for image refinement

In the paper we concentrate on a Wavelet-based technique of image refinement. Specifically, we are aimed to obtain the extended version of an original image while preserving its quality. The image to be expanded is given in a non-compressed gray-scale format. According to the method we propose, original image is, heuristically, supposed to be a smoothed version of an unknown sharp image we try to reach for. The former will be referred to as the superimage, in the sense that it is not just a resized version of the original, but is rendered in more details than the original. This is the case if we derive the details out of the given image. We have found it reasonable to look at the problem in the Wavelet background, as it comprises the image rescaling and feature extraction operations in their natural combination. We offer a number of approaches to the problem, which are supported by the relevant examples. Applications are, at least, expected to arise in the remote sensing image refinement.
SYSADMIN Automating Configuration Troubleshooting with ConfAid

Jason Flinn is an associate professor of computer science and engineering at the University of Michigan. His research interests include operating systems, distributed systems, storage, and mobile computing. jflinn@umich.edu Complex software systems are difficult to configure and manage . When problems inevitably arise, operators spend considerable time troubleshooting those problems by identifying root causes and correcting them . The cost of troubleshooting is substantial . Technical support contributes 17% of the total cost of ownership of today’s desktop computers [3], and troubleshooting misconfigurations is a large part of technical support . Even for casual computer users, troubleshooting is often enormously frustrating .
Pathology and Disruptiveness among Prison Inmates

This article explores the relationship between mental health problems of prison inmates and the inmates' involvement in custodial violations. We find that mentally ill inmates have a higher rate of disciplinary infractions than other inmates, controlling for differences in social and criminal history. There are also indications that the rate of disciplinary infractions varies with the nature, severity, and chronicity of inmate mental health problems. We discuss these findings from a perspective that views disturbed and disruptive behavior as related manifestations of an impaired ability to cope with social situations.
Collective construction of dynamic structure initiated by semi-active blocks

This paper proposes a collective construction method through interaction between simple robots and intelligent blocks that have a rule set and a communication function with neighboring blocks. In our method, the structure is formed by growing chain of blocks. The growth direction is determined by the rule set and a counter value passed between the blocks. The robots load or unload the block based on a simple algorithm and a local signal from the blocks. Because of the simplicity of each robot's behavior, the structure is locally unstable: the blocks can be attached or detached randomly from the structure even if they have already formed a part of the structure. In this paper, we first explain the mechanism of our proposal. Next we show some fundamental characteristics obtained by computer simulation and small scale experiment by real robot and blocks. We introduce small modification to enhance the adaptability of the system mainly focusing on a reinforcement function of the wall against the external stress.
Recommendations for learners are different: Applying memory-based recommender system techniques to lifelong learning

Drachsler, H. , Hummel, H. G. K. , & Koper, R. (2007). Recommendations for learners are different: applying memory-based recommender system techniques to lifelong learning. Paper presented at the SIRTEL workshop at the EC-TEL 2007 Conference. September, 17-20, 2007, Crete, Greece.
Soft updates: a solution to the metadata update problem in file systems

Metadata updates, such as file creation and block allocation, have consistently been identified as a source of performance, integrity, security, and availability problems for file systems. Soft updates is an implementation technique for low-cost sequencing of fine-grained updates to write-back cache blocks. Using soft updates to track and enforce metadata update dependencies, a file system can safely use delayed writes for almost all file operations. This article describes soft updates, their incorporation into the 4.4BSD fast file system, and the resulting effects on the sytem. We show that a disk-based file system using soft updates achieves memory-based file system performance while providing stronger integrity and security guarantees than most disk-based file systems. For workloads that frequently perform updates on metadata (such as creating and deleting files), this improves performance by more than a factor of two and up to a factor of 20 when compared to the conventional synchronous write approach and by 4-19% when compared to an aggressive write-ahead logging approach. In addition, soft updates can improve file system availablity by relegating crash-recovery assistance (e.g., the fsck utility) to an optional and background role, reducing file system recovery time to less than one second.
Actions of SL(n,Z) on homology spheres

Any continuous action of SL(n,Z), where n > 2, on a r-dimensional mod 2 homology sphere factors through a finite group action if r < n - 1. In particular, any continuous action of SL(n+2,Z) on the n-dimensional sphere factors through a finite group action.
Radiosynthesis and Evaluation of [11C-Carbonyl]-Labeled Carbamates as Fatty Acid Amide Hydrolase Radiotracers for Positron Emission Tomography

Fatty acid amide hydrolase (FAAH) plays a key role in regulating the tone of the endocannabinoid system. Radiotracers are required to image and quantify FAAH activity in vivo. We have synthesized a series of potent FAAH inhibitors encompassing two classes of N-alkyl-O-arylcarbamates and radiolabeled eight of them with carbon-11. The [11C-carbonyl]-radiotracers were evaluated in vitro and ex vivo in rats as potential FAAH imaging agents for positron emission tomography (PET). Both sets of [11C]O-arylcarbamates showed good to excellent brain penetration and an appropriate regional distribution. Pretreatments with a FAAH inhibitor demonstrated that 80–95% of brain uptake of radioactivity constituted binding of the radiotracers to FAAH. Brain extraction measurements showed that binding to FAAH was irreversible and kinetically different for the two classes of carbamates. These promising results are discussed in terms of the requirements of a suitable radiotracer for the in vivo imaging of FAAH using PET.
Interspecific scaling of the morphology and posture of the limbs during the locomotion of cats (Felidae)

SUMMARY For phylogenetically diverse mammals, ranging from small rodents to large ungulates, the generalization that limb erectness increases with increased size is supported by some size-dependent scaling relationships of appendicular skeletal anatomy as well as a limited number of direct observations of limb posture during locomotion. If size alone is the causal basis for different limb posture, then the erectness of limbs should increase significantly with increased size within a phylogenetically narrow lineage, but such data are sparse. Thus, to better establish the correlation between size and posture of mammalian limbs, we quantified the scaling relationships between mass and limb dimensions and kinematics during walking of nine species within the felid (cat) clade, which has qualitatively similar limb design. We studied the domestic cat, serval, ocelot, lynx, leopard, cheetah, cougar, lion and tiger, which had masses ranging from <4 kg to nearly 200 kg. Apart from variation associated with overall size, the lengths of the appendicular skeletal structures of most of the felid species were morphologically very similar in multivariate space. The kinematics of the limbs were also relatively uniform, and size had little predictive value for limb posture among felid species. Only three out of a total of 24 angular variables at footfall and midstance changed significantly (0.02<P<0.05) with increased mass. Thus, in contrast to previous broadly comparative studies of mammals, larger species of felids did not have more upright limbs than smaller species.
Isolation of Legionella pneumophila by Centrifugation of Shell Vial Cell Cultures from Multiple Liver and Lung Abscesses

ABSTRACT A 7-year-old girl was admitted to the hospital with acute lymphoblastic leukemia and was treated with allogenic cord blood transplantation. At day 30 after graft, she developed a fever and multiple nodular lesions disseminated in the liver and lungs. All bacterial cultures attempted on liver and lung biopsy specimens and blood remained sterile on standard axenic media. However, inoculation of liver and lung biopsy specimens on eukaryotic cell monolayers by the centrifugation-shell vial technique (M. Marrero and D. Raoult, Am. J. Trop. Med. Hyg. 40:197–199, 1989) led to the recovery of a strain of Legionella pneumophila serogroup 1, identified by 16S rRNA gene amplification and sequencing and serotyping. Our findings demonstrate that the centrifugation-cell culture method, which has previously been useful for the isolation of other strictly or facultatively intracellular bacteria, can also serve as a method for the recovery of L. pneumophila from clinical material.
Genotype vs. Phenotype and the Rise of Non-Communicable Diseases: The Importance of Lifestyle Behaviors During Childhood

Despite continued research and growing public awareness, the incidence of non-communicable diseases (NCD) continues to accelerate. While a person may have a genetic predisposition to certain NCDs, the rapidly changing epidemiology of NCDs points to the importance of environmental, social, and behavioural determinants of health. Specifically, three lifestyle behaviours expose children to important environmental cues and stressors: physical activity, nutritional intake, and sleep behaviour. Failure to expose children to proper gene-environment interactions, through the aforementioned lifestyle behaviours, can and will predispose children to the development of NCDs. Reengineering the environments of children can induce a paradigm shift, from a predominantly biomedical health model of treating symptomology, to a more holistic model based on encouraging appropriate behavioral decisions and optimal health.
On the Evolution of Contacts and Communities in Networks of Face-to-Face Proximity

Communities are a central aspect in the formation of social interaction networks. In this paper, we analyze the evolution of communities in networks of face-to-face proximity. As our application context, we consider four scientific conferences. We compare the basic properties of the contact graphs to describe the properties of the contact networks and analyze the resulting community structure using state-of-the-art automic community detection algorithms. Specifically, we analyze the evolution of contacts and communities over time to consider the stability of the respective communities. In addition, we assess different factors which have an influence on the quality of community prediction. Overall, we provide first important insights into the evolution of contacts and communities in face-to-face contact networks.
Demonstration by FRET of BACE interaction with the amyloid precursor protein at the cell surface and in early endosomes

Amyloid-β peptide, which accumulates in senile plaques in Alzheimer's disease, is derived from the amyloid precursor protein (APP) by proteolytic processing. β-secretase (Asp2), which cleaves APP at the N-terminus of amyloid-β, has recently been identified to be the protease BACE. In the present study, we examined the subcellular localization of interactions between APP and BACE by using both double immunofluorescence and a fluorescence resonance energy transfer (FRET) approach. Cell surface APP and BACE, studied by using antibodies directed against their ectodomains in living H4 neuroglioma cells co-transfected with APP and BACE, showed exquisite co-localization and demonstrated a very close interaction by FRET analysis. The majority of cell surface APP and BACE were internalized after 15 minutes, but they remained strongly co-localized together in the early endosomal compartment, where FRET analysis demonstrated a continued close interaction. By contrast, at later timepoints, almost no co-localization or FRET was observed in lysosomal compartments. To determine whether the APP-BACE interaction on cell surface and endosomes contributed to amyloid-β synthesis, we labeled cell surface APP and demonstrated detectable levels of labeled amyloid-β within 30 minutes. APP-Swedish mutant protein enhanced amyloid-β synthesis from cell surface APP, consistent with the observation that it is a better BACE substrate than wild-type APP. Taken together, these data confirm a close APP-BACE interaction in early endosomes, and highlight the cell surface as an additional potential site of APP-BACE interaction.
Causes and consequences of inadequate management of acute pain.

CONTEXT Intense acute pain afflicts millions of patients each year. Despite the recently increased focus on the importance of pain control, management of acute pain has remained suboptimal. OBJECTIVE The objective of this study was to identify through a review of recent literature the barriers to effective treatment of acute pain and the potential consequences of inadequate pain management. DESIGN A comprehensive literature review was conducted to identify articles relevant to the management of acute pain. Information regarding the underlying causes of inadequate pain management, as well as the sequelae associated with undermanaged pain was extracted and summarized. RESULTS Studies indicate that treatment of acute pain remains suboptimal due to attitudes and educational barriers on the part of both physicians and patients, as well as the intrinsic limitations of available therapies. Inadequate management of acute pain negatively impacts numerous aspects of patient health, and may increase the risk of developing chronic pain. Although opioids are the preferred treatment for most moderate to severe acute pain, their side effects can impede their use, and thus, their clinical effectiveness. Analgesic regimens with an improved efficacy/tolerability balance have the potential to improve acute pain management, and thus reduce the incidence of chronic pain. Studies examining the use of multiple analgesics with different mechanisms of action suggest that multimodal therapies may offer an improved efficacy/tolerability balance over single agent regimens. CONCLUSIONS There exists a significant need for effective, well-tolerated analgesic therapies to limit the negative consequences of undermanaged acute pain. The use of multimodal therapy has demonstrated increasing promise and is supported by current practice guidelines.
Molecular cloning and sequence analysis of the endochitinase from Chaetomium cupreum

Endochitinase gene fragment of Chaetomium cupreum (designated Chi46) obtained by construction of C. cupreum mycelium cDNA library. Its full-length cDNA was cloned by PCR. The results showed that the open reading frame of Chi46 was 1350bp and encoded a putative protein of 449 amino acids residues with s molecular mass of 46kDa. Bioinformatics analysis revealed that protein sequence of Chi46 containing a 22-residue secretion signal sequence and had a high degree of similarity with C. globosum chitinase. The domain search program at the NCBI and Pfam server showed that Chi46 protein had the glycosyl-hydrolase-18 conserved domain. Additionally, the deduced amino acid sequence had the same catalytic domain and substrate binding site with ech42 of Trichoderma harzianum.
How effective are school bullying intervention programs? A meta-analysis of intervention research.

Research on effectiveness of school bullying interventions has lagged behind descriptive studies on this topic. The literature on bullying intervention research has only recently expanded to a point that allows for synthesis of findings across studies. The authors conducted a meta-analytic study of school bullying intervention research across the 25-year period from 1980 through 2004, identifying 16 studies that met our inclusion criteria. These studies included 15,386 K through 12 student participants from European nations and the United States. Applying standard meta-analysis techniques to obtain averaged effect size estimates across similar outcomes, the authors found that the intervention studies produced meaningful and clinically important positive effects for about one-third of the variables. The majority of outcomes evidenced no meaningful change, positive or negative. The authors conclude that school bullying interventions may produce modest positive outcomes, that they are more likely to influence knowledge, attitudes, and self-perceptions rather than actual bullying behaviors; and that the majority of outcome variables in intervention studies are not meaningfully impacted.
From professional development to system change: teacher leadership and innovation

This article argues for a particular conceptualisation of teacher leadership; one that enables us to overcome the limitations of established approaches to continuing professional development as a strategy for school improvement by mobilising the massive untapped potential of teachers as leaders of innovation. In this article, teacher leadership is conceived as a key dimension of the role of teachers regardless of special roles and responsibilities in the organisational structures of their schools. Evidence to support this argument is drawn from the International Teacher Leadership project, which has partners in 15 countries as diverse as Kosovo and New Zealand. The International Teacher Leadership project builds on a model developed in the United Kingdom (The HertsCam Network) to develop support for teacher leadership as an educational reform strategy. The article explores the professional learning arising for the teachers and offers a theory of educational innovation within which it is located.