Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional Factor NF-κB as a Target for Therapy in Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative condition characterized by chronic inflammation. Nuclear factor κB (NF-κB) is a family of inducible transcription factors that are expressed in a wide variety of cells and tissues, including microglia, astrocytes, and neurons, and the classical NF-κB pathway plays a key role in the activation and regulation of inflammatory mediator production during inflammation. Activation of the classical NF-κB pathway is mediated through the activity of the IKK kinase complex, which consists of a heterotrimer of IKKα, IKKβ, and IKKγ subunits. Targeting NF-κB has been proposed as an approach to the treatment of acute and chronic inflammatory conditions, and the use of inhibitors specific for either IKKβ or IKKγ has now been found to inhibit neurodegeneration of TH+ DA-producing neurons in murine and primate models of Parkinson's disease. These studies suggest that targeting the classical pathway of NF-κB through the inhibition of the IKK complex can serve as a useful therapeutic approach to the treatment of PD.
Proteoglycan and glycosaminoglycan synthesis in embryonic mouse salivary glands: effects of beta-D-xyloside, an inhibitor of branching morphogenesis

The proteoglycans and glycosaminoglycans synthesized by embryonic mouse salivary glands during normal morphogenesis and in the presence of beta- xyloside, an inhibitor of branching morphogenesis, have been partially characterized. Control and rho-nitrophenyl-beta-D-xyloside-treated salivary rudiments synthesize proteoglycans that are qualitatively similar, based on mobility on Sepharose CL-4B under dissociative conditions and glycosaminoglycan composition. However, beta-xyloside inhibits total proteoglycan-associated glycosaminoglycan synthesis by 50%, and also stimulates synthesis of large amounts of free chondroitin (dermatan) sulfate. This free glycosaminoglycan accounts for the threefold stimulation of total glycosaminoglycan synthesis in beta- xyloside-treated cultures. Several observations suggest that the disruption of proteoglycan synthesis rather than the presence of large amounts of free glycosaminoglycan is responsible for the inhibition of branching morphogenesis. (a) We have been unable to inhibit branching activity by adding large amounts of chondroitin (dermatan) sulfate, extracted from beta-xyloside-treated cultures, to the medium of salivary rudiments undergoing morphogenesis. (b) In the range of 0.1- 0.4 mM beta-xyloside, the dose-dependent inhibition of branching morphogenesis is directly correlated with the inhibition of proteoglycan synthesis. The stimulation of free glycosaminoglycan synthesis is independent of dose in this range, since stimulation is maximal even at the lowest concentration used, 0.1 mM. The data strongly suggest that the inhibition of branching morphogenesis is caused by the disruption of proteoglycan synthesis in beta-xyloside- treated salivary glands.
Synovial Biomarkers in Psoriatic Arthritis

Objective. To find candidate biomarkers of psoriatic arthritis (PsA). A panel of synovial fluid (SF) and synovial tissue (ST) biomarkers was analyzed in patients with resistant peripheral PsA, in relation to clinical and imaging outcomes of synovitis response following serial intraarticular (IA) etanercept injections (12.5 mg). Methods. Fourteen PsA patients with resistant knee joint synovitis were treated with 4 IA etanercept injections in a single knee joint, once every 2 weeks. Primary outcome (Thompson’s knee index: THOMP) and secondary outcomes were assessed at baseline and end of study: C-reactive protein, Knee Joint Articular Index (KJAI), Health Assessment Questionnaire disability index, maximal synovial thickness (MST) by gray-scale ultrasonography, contrast-enhanced magnetic resonance imaging (C+MRI), ST-cluster differentiation (CD)45+ mononuclear cell, ST-CD31+ vessels, and ST-CD105+ angiogenic endothelial cells, along with levels of SF interleukin 1ß (IL-1ß), IL-1 receptor antagonist (Ra), and IL-6. Results. At the end of the study, clinical and imaging outcomes, ST and SF biological markers were significantly reduced compared to baseline. There was a significant association between IL-6 and either THOMP or KJAI; between either ST-CD31+ or ST-CD105+ or ST-CD45+; between ST and SF biomarkers expression (CD45+ and IL-1ß) and between ST-CD45+ and both KJAI and MRI-MST. Comparing pre- versus post-IA etanercept injection changes (Δ), Δ IL-1ß was significantly correlated with both Δ IL-6 and with Δ IL-1Ra and Δ IL-6 with Δ IL-1Ra. Conclusion. The association to disease activity and the changes following IA treatment indicate that ST-CD45+ and ST-CD31+, along with SF-IL-6 and SF-IL-1ß, may represent candidate biomarkers of the knee synovitis response to IA tumor necrosis factor-α blockade.
Specific Inhibition of the Classical Complement Pathway by C1q-Binding Peptides1

Undesired activation of the complement system is a major pathogenic factor contributing to various immune complex diseases and conditions such as hyperacute xenograft rejection. We aim for prevention of complement-mediated damage by specific inhibition of the classical complement pathway, thus not affecting the antimicrobial functions of the complement system via the alternative pathway and the lectin pathway. Therefore, 42 peptides previously selected from phage-displayed peptide libraries on basis of C1q binding were synthesized and examined for their ability to inhibit the function of C1q. From seven peptides that showed inhibition of C1q hemolytic activity but no inhibition of the alternative complement pathway, one peptide (2J) was selected and further studied. Peptide 2J inhibited the hemolytic activity of C1q from human, chimpanzee, rhesus monkey, rat, and mouse origin, all with a similar dose-response relationship (IC50 2–6 μM). Binding of C1q to peptide 2J involved the globular head domain of C1q. In line with this interaction, peptide 2J dose-dependently inhibited the binding of C1q to IgG and blocked activation of C4 and C3 and formation of C5b-9 induced via classical pathway activation, as assessed by ELISA. Furthermore, the peptide strongly inhibited the deposition of C4 and C3 on pig cells following their exposure to human xenoreactive Abs and complement. We conclude that peptide 2J is a promising reagent for the development of a therapeutic inhibitor of the earliest step of the classical complement pathway, i.e., the binding of C1q to its target.
Expression of tissue transglutaminase in Balb-C 3T3 fibroblasts: effects on cellular morphology and adhesion

Tissue transglutaminase is a cytosolic enzyme whose primary function is to catalyze the covalent cross-linking of proteins. To investigate the functions of this enzyme in physiological systems, we have established lines of Balb-C 3T3 fibroblasts stably transfected with a constitutive tissue transglutaminase expression plasmid. Several cell lines expressing high levels of catalytically active tissue transglutaminase have been isolated and characterized. Transglutaminase-transfected cells showed morphologic features quite distinct from their nontransfected counterparts. Many of the cells showed an extended and very flattened morphology that reflected increased adhesion of the cells to the substratum. Other cells, particularly those showing the highest levels of intracellular transglutaminase expression, showed extensive membrane blebbing and cellular fragmentation. The results of these experiments suggest that the induction and activation of tissue transglutaminase may contribute both to changes in cellular morphology and adhesiveness.
2012.2783-JRC RR CBA for Smart Grids (online)

The goal of this report is to provide guidance and advice for conducting cost-benefit analyses of Smart Grid projects. The assessment framework is structured into a set of guidelines to tailor assumptions to local conditions, to identify and monetise benefits and costs, and to perform a sensitivity analysis of the most critical variables. It also provides guidance in the identification of externalities and social impacts that can result from the implementation of Smart Grid projects but that cannot be easily monetised and factored into the cost-benefit computation. A European Smart Grid project (InovGrid, implemented in Portugal) has been used as a case study to fine-tune and illustrate the proposed assessment framework. How to obtain EU publications Our priced publications are available from EU Bookshop (http://bookshop.europa.eu), where you can place an order with the sales agent of your choice. The Publications Office has a worldwide network of sales agents. You can obtain their contact details by sending a fax to (352) 29 29-42758.
Central venous catheters: incidence and predictive factors of venous thrombosis

Aims: Central venous catheter access in an acute setting can be a challenge given underlying disease and risk for venous thrombosis. Peripherally inserted central venous catheters (PICCs) are commonly placed but limit sites for fistula creation in patients with chronic renal failure (CKD). The aim of this study is to determine the incidence of venous thrombosis from small bore internal jugular (SBIJ) and PICC line placement. This investigation identifies populations of patients who may not be ideal candidates for a PICC and highlights the importance of peripheral vein preservation in patients with renal failure. Materials and methods: A venous Doppler ultrasound was performed at the time of SBIJ insertion and removal to evaluate for thrombosis in the internal jugular vein. Data was collected pre- and post-intervention to ascertain if increased vein preservation knowledge amongst the healthcare team led to less use of PICCs. Demographic factors were collected in the SBIJ and PICC groups and risk factor analysis was completed. Results: 1,122 subjects had PICC placement and 23 had SBIJ placement. The incidence of thrombosis in the PICC group was 10%. One patient with an SBIJ had evidence of central vein thrombosis when the catheter was removed. Univariate and multivariate analysis demonstrated a history of transplant, and the indication of total parenteral nutrition was associated with thrombosis (p < 0.001). The decrease in PICCs placed in patients with CKD 6 months before and after intervention was significant (p < 0.05). Conclusions: There are subsets of patients with high risk for thrombosis who may not be ideal candidates for a PICC.
The Neandertal type site revisited: Interdisciplinary investigations of skeletal remains from the Neander Valley, Germany

The 1856 discovery of the Neandertal type specimen (Neandertal 1) in western Germany marked the beginning of human paleontology and initiated the longest-standing debate in the discipline: the role of Neandertals in human evolutionary history. We report excavations of cave sediments that were removed from the Feldhofer caves in 1856. These deposits have yielded over 60 human skeletal fragments, along with a large series of Paleolithic artifacts and faunal material. Our analysis of this material represents the first interdisciplinary analysis of Neandertal remains incorporating genetic, direct dating, and morphological dimensions simultaneously. Three of these skeletal fragments fit directly on Neandertal 1, whereas several others have distinctively Neandertal features. At least three individuals are represented in the skeletal sample. Radiocarbon dates for Neandertal 1, from which a mtDNA sequence was determined in 1997, and a second individual indicate an age of ≈40,000 yr for both. mtDNA analysis on the same second individual yields a sequence that clusters with other published Neandertal sequences.
On the influence of selection operators on performances in cellular Genetic Algorithms

In this paper, we study the influence of the selective pressure on the performance of cellular genetic algorithms. Cellular genetic algorithms are genetic algorithms where the population is embedded on a toroidal grid. This structure makes the propagation of the best so far individual slow down, and allows to keep in the population potentially good solutions. We present two selective pressure reducing strategies in order to slow down even more the best solution propagation. We experiment these strategies on a hard optimization problem, the quadratic assignment problem, and we show that there is a threshold value of the control parameter for both which gives the best performance. This optimal value does not find explanation on the selective pressure only, measured either by takeover time or diversity evolution. This study makes us conclude that we need other tools than the sole selective pressure measures to explain the performance of cellular genetic algorithms.
Approximating Concavely Parameterized Optimization Problems

We consider an abstract class of optimization problems that are parameterized concavely in a single parameter, and show that the solution path along the parameter can always be approximated with accuracy e > 0 by a set of size O(1/√e). A lower bound of size Ω(1/√e) shows that the upper bound is tight up to a constant factor. We also devise an algorithm that calls a step-size oracle and computes an approximate path of size O(1/√e). Finally, we provide an implementation of the oracle for soft-margin support vector machines, and a parameterized semi-definite program for matrix completion.
Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging.

OBJECTIVE Infantile autism is a neurobehavioral disorder that is widely believed to have etiologically distinct subtypes, including subtypes with a genetic basis, but no neuroanatomic evidence firmly supports this belief. To date, only one type of cerebellar abnormality has been identified in patients with autism: hypoplasia of the vermis and hemispheres. By using a large sample of autistic patients and healthy volunteers along with precise MR imaging and quantitative procedures, we sought to replicate previous reports of cerebellar vermian hypoplasia in autism and to identify additional subtypes of cerebellar abnormality. MATERIALS AND METHODS Using MR technology, we imaged and measured posterior and anterior vermian regions in 50 autistic patients (2-40 years old) and 53 healthy control subjects (3-37 years old). The autistic patients had social, language, cognitive, behavioral, and medical history characteristics that were typical of the general autistic population. By using precise procedures for positioning and aligning MR slices, we obtained comparable MR images within and across subject groups. RESULTS Statistical analyses showed two subgroups of autistic patients, one (86% of the patients) with findings consistent with vermian hypoplasia and another (12% of the patients) with evidence of vermian hyperplasia. The hypoplasia subgroup included 43 patients whose mean midsagittal area for vermian lobules VI and VII was 237 +/- 38 mm2, and the hyperplasia subgroup included six patients whose mean area was 377 +/- 12 mm2. Thus, the area of lobules VI and VII in the hypoplasia subgroup was 16% smaller than the mean area in the control subjects (282 +/- 42 mm2) (p < .0001), whereas that in the hyperplasia subgroup was 34% larger (p < .0001). Analyses showed that these two subtypes of vermian abnormalities were present across all ages of autistic patients studied. CONCLUSION Two different subtypes of autistic patients can be identified on the basis of the presence of vermian hypoplasia or hyperplasia as seen on MR images. Possible origins for vermian hypoplasia include environmental trauma and genetic factors.
Survey: Multiword Expression Processing: A Survey

Multiword expressions (MWEs) are a class of linguistic forms spanning conventional word boundaries that are both idiosyncratic and pervasive across different languages. The structure of linguistic processing that depends on the clear distinction between words and phrases has to be re-thought to accommodate MWEs. The issue of MWE handling is crucial for NLP applications, where it raises a number of challenges. The emergence of solutions in the absence of guiding principles motivates this survey, whose aim is not only to provide a focused review of MWE processing, but also to clarify the nature of interactions between MWE processing and downstream applications. We propose a conceptual framework within which challenges and research contributions can be positioned. It offers a shared understanding of what is meant by “MWE processing,” distinguishing the subtasks of MWE discovery and identification. It also elucidates the interactions between MWE processing and two use cases: Parsing and machine translation. Many of the approaches in the literature can be differentiated according to how MWE processing is timed with respect to underlying use cases. We discuss how such orchestration choices affect the scope of MWE-aware systems. For each of the two MWE processing subtasks and for each of the two use cases, we conclude on open issues and research perspectives.
Oxygen-Poor Microzones as Potential Sites of Microbial N2 Fixation in Nitrogen-Depleted Aerobic Marine Waters

The nitrogen-deficient coastal waters of North Carolina contain suspended bacteria potentially able to fix N2. Bioassays aimed at identifying environmental factors controlling the development and proliferation of N2 fixation showed that dissolved organic carbon (as simple sugars and sugar alcohols) and particulate organic carbon (derived from Spartina alterniflora) additions elicited and enhanced N2 fixation (nitrogenase activity) in these waters. Nitrogenase activity occurred in samples containing flocculent, mucilage-covered bacterial aggregates. Cyanobacterium-bacterium aggregates also revealed N2 fixation. In all cases bacterial N2 fixation occurred in association with surficial microenvironments or microzones. Since nitrogenase is oxygen labile, we hypothesized that the aggregates themselves protected their constituent microbes from O2. Microelectrode O2 profiles revealed that aggregates had lower internal O2 tensions than surrounding waters. Tetrazolium salt (2,3,5-triphenyl-3-tetrazolium chloride) reduction revealed that patchy zones existed both within microbes and extracellularly in the mucilage surrounding microbes where free O2 was excluded. Triphenyltetrazolium chloride reduction also strongly inhibited nitrogenase activity. These findings suggest that N2 fixation is mediated by the availability of the appropriate types of reduced microzones. Organic carbon enrichment appears to serve as an energy and structural source for aggregate formation, both of which were required for eliciting N2 fixation responses of these waters.
Two Distinct Neuronal Networks Mediate the Awareness of Environment and of Self

Evidence from functional neuroimaging studies on resting state suggests that there are two distinct anticorrelated cortical systems that mediate conscious awareness: an “extrinsic” system that encompasses lateral fronto-parietal areas and has been linked with processes of external input (external awareness), and an “intrinsic” system which encompasses mainly medial brain areas and has been associated with internal processes (internal awareness). The aim of our study was to explore the neural correlates of resting state by providing behavioral and neuroimaging data from healthy volunteers. With no a priori assumptions, we first determined behaviorally the relationship between external and internal awareness in 31 subjects. We found a significant anticorrelation between external and internal awareness with a mean switching frequency of 0.05 Hz (range: 0.01–0.1 Hz). Interestingly, this frequency is similar to BOLD fMRI slow oscillations. We then evaluated 22 healthy volunteers in an fMRI paradigm looking for brain areas where BOLD activity correlated with “internal” and “external” scores. Activation of precuneus/posterior cingulate, anterior cingulate/mesiofrontal cortices, and parahippocampal areas (“intrinsic system”) was linearly linked to intensity of internal awareness, whereas activation of lateral fronto-parietal cortices (“extrinsic system”) was linearly associated with intensity of external awareness.
On Probabilistic Shaping of Quadrature Amplitude Modulation for the Nonlinear Fiber Channel

Different aspects of probabilistic shaping for a multispan optical communication system are studied. First, a numerical analysis of the additive white Gaussian noise (AWGN) channel investigates the effect of using a small number of input probability mass functions (PMFs) for a range of signal-to-noise ratios (SNRs), instead of optimizing the constellation shaping for each SNR. It is shown that if a small penalty of at most 0.1 dB SNR to the full shaping gain is acceptable, just two shaped PMFs are required per quadrature amplitude modulation (QAM) over a large SNR range. For a multispan wavelength division multiplexing optical fiber system with 64QAM input, it is shown that just one PMF is required to achieve large gains over uniform input for distances from 1400 to 3000 km. Using recently developed theoretical models that extend the Gaussian noise (GN) model and full-field split-step simulations, we illustrate the ramifications of probabilistic shaping on the effective SNR after fiber propagation. Our results show that, for a fixed average optical launch power, a shaping gain is obtained for the noise contributions from fiber amplifiers and modulation-independent nonlinear interference (NLI), whereas shaping simultaneously causes a penalty as it leads to an increased NLI. However, this nonlinear shaping loss is found to have a relatively minor impact, and optimizing the shaped PMF with a modulation-dependent GN model confirms that the PMF found for AWGN is also a good choice for a multi-span fiber system.
Optical molecular imaging in drug discovery and clinical development

Recently, the drug discovery process has greatly benefited from a wealth of novel druggable targets following the sequencing of the human genome and the parallel development of combinatorial chemistry and high-throughput screening technologies. The large number of drug candidates generated by this combined approach requires an evolution and refinement of in vivo measurement methodologies and animal models to cope with this flux of novel compounds. At the same time, drug developers are looking for translational biomarkers that can facilitate the clinical evaluation of the most promising molecules. Imaging technologies are particularly well suited to help address these various challenges. The authors focus the interest of this review on optical molecular imaging technology as well as reviewing how this technology is being integrated in various therapeutic areas, and how it has started to impact the preclinical drug discovery process. Finally, the potential clinical applications of optical molecular imaging are discussed.
Spectral subband centroid features for speech recognition

Cepstral coefficients derived either through linear prediction (LP) analysis or from filter banks are perhaps the most commonly used features in currently available speech recognition systems. In this paper, we propose spectral subband centroids as new features and use them as a supplement to cepstral features for speech recognition. We show that these features have properties similar to formant frequencies and they are quite robust to noise. Recognition results are reported, justifying the usefulness of these features as supplementary features.