Differential aberrant sprouting in temporal lobe epilepsy with psychiatric co-morbidities

Psychiatric co-morbidities in epilepsy are common in patients with temporal lobe epilepsy (TLE). Pathological alterations in TLE are well characterised; however, neuropathologic data are relatively scale regarding the association between psychiatric diseases and epilepsy. Our objective was to evaluate the clinical data of 46 adult TLE patients with and without psychiatric co-morbidities and to correlate the data with hippocampal neuronal density and mossy fiber sprouting. Accordingly, patients were grouped as follows: TLE patients without history of psychiatric disorder (TLE, n = 16), TLE patients with interictal psychosis (TLE + P, n = 14), and TLE patients with major depression (TLE + D, n = 16). Hippocampi from autopsies served as non-epileptic controls (n = 10). TLE + P exhibited significantly diminished mossy fiber sprouting and decreased neuronal density in the entorhinal cortex when compared with TLE. TLE + P showed significantly poorer results in verbal memory tasks. TLE + D exhibited significantly increased mossy fiber sprouting length when compared with TLE and TLE + P. Further, a higher proportion of TLE + D and TLE + P presented secondarily generalised seizures than did TLE. Our results indicate that TLE patients with psychiatric disorders have distinct features when compared with TLE patients without psychiatric co-morbidities and that these changes may be involved in either the manifestation or the maintenance of psychiatric co-morbidities in epilepsy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Differential MiRNA expression in childhood acute lymphoblastic leukemia and association with clinical and biological features

The present study aimed to analyze the expression profile of the microRNAs previously described as associated with childhood ALL, miR-92a, miR-100, miR-125a-5p, miR-128a, miR-181b, miR-196b and let-7e, and their association with biological/prognostic features in 128 consecutive samples of childhood acute lymphoblastic leukemia (ALL) by quantitative real-time PCR. A significant association was observed between higher expression levels of miR-196b and T-ALL, miR-100 and patients with low white blood cell count at diagnosis and t(12;21) positive ALL. These findings suggest a potential activity of these microRNAs in pediatric ALL biology. (C) 2011 Elsevier Ltd. All rights reserved.

Expanding the differential diagnosis of inherited neuropathies with non-uniform conduction: Andermann syndrome

Uniform conduction slowing has been considered a characteristic of inherited demyelinating neuropathies. We present an 18-year-old girl, born from first cousins, that presented a late motor and psychological development, cerebellar ataxia, facial diplegia, abnormal eye movement, scoliosis, and corpus callosum agenesis, whose compound muscle action potentials were slowed and dispersed. A mutation was found on KCC3 gene, confirming Andermann syndrome, a disease that must be included in the differential diagnosis of inherited neuropathies with non-uniform conduction slowing.

The Differential Clinical Impact of Human Coronavirus Species in Children With Cystic Fibrosis

We investigated the clinical impact of human coronaviruses (HCoV) OC43, 229E, HKU1 and NL63 in pediatric patients with cystic fibrosis (CF) during routine and exacerbation visits. A total of 408 nasopharyngeal aspirate samples were obtained from 103 patients over a 1-year period. Samples positive for HCoV were submitted for nucleotide sequencing to determine the species. Nineteen samples (4.65%) were positive for HCoV, of which 8 were positive for NL63, 6 for OC43, 4 for HKU1, and 1 for 229E. Identification of HCoV was not associated with an increased rate of respiratory exacerbations, but NL63-positive patients had higher exacerbation rates than patients who were positive for other HCoV species.

Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX plus Tumor Necrosis Factor Inhibitor Combined Therapy

Objective. We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-alpha (anti-TNF) combined therapy. Methods. We evaluated 25 patients with RA taking MTX 15-20 mg/week as a monotherapy (8 responders and 17 nonresponders). All MTX nonresponders received intliximab and were reassessed after 20 weeks to evaluate their anti-TNF responsiveness using the European League Against Rheumatism response criteria. A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program. Results. Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti-TNF responders from nonresponders. The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders. In MTX plus anti-TNF nonresponders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders. Conclusion. Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1 CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti-TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study. (First Release July 1 2012; J Rheumatol 2012;39:1524-32; doi:10.3899/jrheum.120092)

Different levels of MT-I/II between patients with MTLE with or without seizure generalization: does hippocampal MT-I/II affects seizure spread, or does seizure spread promotes differential expression of MT-I/II?

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) were evaluated for expression of MT-I/II and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis and reduced neuronal population. MT-I/II levels did not correlate with any clinical variables, but patients with secondary generalized seizures (SGS) had less MT-I/II than patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from MTLE patients and our data suggest that it may be associated with different seizure spread patterns.

Differential inflammasome expression and IL-1β secretion in monocyte-derived dendritic cells differentiated with IL-4 or IFN-α

NLRP3-inflammasome activation was evaluated in monocyte-derived dendritic cells (DC) obtained through IL-4 (IL4-DC) or IFN-α (IFN-DC) protocols and pulsed with chemically inactivated HIV-1. Inflammasome' genes expression and IL-1β secretion were compared in DC isolated from 15 healthy subjects (HC) and 10 HIV-1 infected individuals (HIV+). FINDINGS: Whether HIV was able to increased NLRP3-inflammasome genes expression and IL-1β secretion in IL4-DC from HC, the induction of inflammasome appeared significantly reduced in IFN-DC from HC, suggesting a different responsive state of IFN-DC compared to IL4-DC. No inflammasome activation was observed in IL4-DC as well as in IFN-DC derived from HIV + subjects, confirming previous findings on "unresponsive" state of DC derived from HIV + possibly due to chronic inflammatory state of these individuals. CONCLUSIONS: Our results showed that IFN-α differently modulates inflammasome expression during monocytes-DC in vitro differentiation. These findings could be of interest considering the on-going research about DC manipulation and therapeutic strategies for HIV + involving DC-based immune-vaccines.

Retrieval of trace gases vertical profile in the lower atmosphere combining. Differential Optical Absorption Spectroscopy with radiative transfer models

The motivation for the work presented in this thesis is to retrieve profile information for the atmospheric trace constituents nitrogen dioxide (NO2) and ozone (O3) in the lower troposphere from remote sensing measurements. The remote sensing technique used, referred to as Multiple AXis Differential Optical Absorption Spectroscopy (MAX-DOAS), is a recent technique that represents a significant advance on the well-established DOAS, especially for what it concerns the study of tropospheric trace consituents. NO2 is an important trace gas in the lower troposphere due to the fact that it is involved in the production of tropospheric ozone; ozone and nitrogen dioxide are key factors in determining the quality of air with consequences, for example, on human health and the growth of vegetation. To understand the NO2 and ozone chemistry in more detail not only the concentrations at ground but also the acquisition of the vertical distribution is necessary. In fact, the budget of nitrogen oxides and ozone in the atmosphere is determined both by local emissions and non-local chemical and dynamical processes (i.e. diffusion and transport at various scales) that greatly impact on their vertical and temporal distribution: thus a tool to resolve the vertical profile information is really important. Useful measurement techniques for atmospheric trace species should fulfill at least two main requirements. First, they must be sufficiently sensitive to detect the species under consideration at their ambient concentration levels. Second, they must be specific, which means that the results of the measurement of a particular species must be neither positively nor negatively influenced by any other trace species simultaneously present in the probed volume of air. Air monitoring by spectroscopic techniques has proven to be a very useful tool to fulfill these desirable requirements as well as a number of other important properties. During the last decades, many such instruments have been developed which are based on the absorption properties of the constituents in various regions of the electromagnetic spectrum, ranging from the far infrared to the ultraviolet. Among them, Differential Optical Absorption Spectroscopy (DOAS) has played an important role. DOAS is an established remote sensing technique for atmospheric trace gases probing, which identifies and quantifies the trace gases in the atmosphere taking advantage of their molecular absorption structures in the near UV and visible wavelengths of the electromagnetic spectrum (from 0.25 μm to 0.75 μm). Passive DOAS, in particular, can detect the presence of a trace gas in terms of its integrated concentration over the atmospheric path from the sun to the receiver (the so called slant column density). The receiver can be located at ground, as well as on board an aircraft or a satellite platform. Passive DOAS has, therefore, a flexible measurement configuration that allows multiple applications. The ability to properly interpret passive DOAS measurements of atmospheric constituents depends crucially on how well the optical path of light collected by the system is understood. This is because the final product of DOAS is the concentration of a particular species integrated along the path that radiation covers in the atmosphere. This path is not known a priori and can only be evaluated by Radiative Transfer Models (RTMs). These models are used to calculate the so called vertical column density of a given trace gas, which is obtained by dividing the measured slant column density to the so called air mass factor, which is used to quantify the enhancement of the light path length within the absorber layers. In the case of the standard DOAS set-up, in which radiation is collected along the vertical direction (zenith-sky DOAS), calculations of the air mass factor have been made using “simple” single scattering radiative transfer models. This configuration has its highest sensitivity in the stratosphere, in particular during twilight. This is the result of the large enhancement in stratospheric light path at dawn and dusk combined with a relatively short tropospheric path. In order to increase the sensitivity of the instrument towards tropospheric signals, measurements with the telescope pointing the horizon (offaxis DOAS) have to be performed. In this circumstances, the light path in the lower layers can become very long and necessitate the use of radiative transfer models including multiple scattering, the full treatment of atmospheric sphericity and refraction. In this thesis, a recent development in the well-established DOAS technique is described, referred to as Multiple AXis Differential Optical Absorption Spectroscopy (MAX-DOAS). The MAX-DOAS consists in the simultaneous use of several off-axis directions near the horizon: using this configuration, not only the sensitivity to tropospheric trace gases is greatly improved, but vertical profile information can also be retrieved by combining the simultaneous off-axis measurements with sophisticated RTM calculations and inversion techniques. In particular there is a need for a RTM which is capable of dealing with all the processes intervening along the light path, supporting all DOAS geometries used, and treating multiple scattering events with varying phase functions involved. To achieve these multiple goals a statistical approach based on the Monte Carlo technique should be used. A Monte Carlo RTM generates an ensemble of random photon paths between the light source and the detector, and uses these paths to reconstruct a remote sensing measurement. Within the present study, the Monte Carlo radiative transfer model PROMSAR (PROcessing of Multi-Scattered Atmospheric Radiation) has been developed and used to correctly interpret the slant column densities obtained from MAX-DOAS measurements. In order to derive the vertical concentration profile of a trace gas from its slant column measurement, the AMF is only one part in the quantitative retrieval process. One indispensable requirement is a robust approach to invert the measurements and obtain the unknown concentrations, the air mass factors being known. For this purpose, in the present thesis, we have used the Chahine relaxation method. Ground-based Multiple AXis DOAS, combined with appropriate radiative transfer models and inversion techniques, is a promising tool for atmospheric studies in the lower troposphere and boundary layer, including the retrieval of profile information with a good degree of vertical resolution. This thesis has presented an application of this powerful comprehensive tool for the study of a preserved natural Mediterranean area (the Castel Porziano Estate, located 20 km South-West of Rome) where pollution is transported from remote sources. Application of this tool in densely populated or industrial areas is beginning to look particularly fruitful and represents an important subject for future studies.

Partial melting within the lower crust – Constraints from bulk rock geochemical data and trace element mineral analyses of granulites and migmatites from Central Finland

This PhD thesis concerns geochemical constraints on recycling and partial melting of Archean continental crust. A natural example of such processes was found in the Iisalmi area of Central Finland. The rocks from this area are Middle to Late Archean in age and experienced metamorphism and partial melting between 2.7-2.63 Ga. The work is based on extensive field work. It is furthermore founded on bulk rock geochemical data as well as in-situ analyses of minerals. All geochemical data were obtained at the Institute of Geosciences, University of Mainz using X-ray fluorescence, solution ICP-MS and laser ablation-ICP-MS for bulk rock geochemical analyses. Mineral analyses were accomplished by electron microprobe and laser ablation ICP-MS. Fluid inclusions were studied by microscope on a heating-freezing-stage at the Geoscience Center, University Göttingen. Part I focuses on the development of a new analytical method for bulk rock trace element determination by laser ablation-ICP-MS using homogeneous glasses fused from rock powder on an Iridium strip heater. This method is applicable for mafic rock samples whose melts have low viscosities and homogenize quickly at temperatures of ~1200°C. Highly viscous melts of felsic samples prevent melting and homogenization at comparable temperatures. Fusion of felsic samples can be enabled by addition of MgO to the rock powder and adjustment of melting temperature and melting duration to the rock composition. Advantages of the fusion method are low detection limits compared to XRF analyses and avoidance of wet-chemical processing and use of strong acids as in solution ICP-MS as well as smaller sample volumes compared to the other methods. Part II of the thesis uses bulk rock geochemical data and results from fluid inclusion studies for discrimination of melting processes observed in different rock types. Fluid inclusion studies demonstrate a major change in fluid composition from CO2-dominated fluids in granulites to aqueous fluids in TTG gneisses and amphibolites. Partial melts were generated in the dry, CO2-rich environment by dehydration melting reactions of amphibole which in addition to tonalitic melts produced the anhydrous mineral assemblages of granulites (grt + cpx + pl ± amph or opx + cpx + pl + amph). Trace element modeling showed that mafic granulites are residues of 10-30 % melt extraction from amphibolitic precursor rocks. The maximum degree of melting in intermediate granulites was ~10 % as inferred from modal abundances of amphibole, clinopyroxene and orthopyroxene. Carbonic inclusions are absent in upper-amphibolite facies migmatites whereas aqueous inclusion with up to 20 wt% NaCl are abundant. This suggests that melting within TTG gneisses and amphibolites took place in the presence of an aqueous fluid phase that enabled melting at the wet solidus at temperatures of 700-750°C. The strong disruption of pre-metamorphic structures in some outcrops suggests that the maximum amount of melt in TTG gneisses was ~25 vol%. The presence of leucosomes in all rock types is taken as the principle evidence for melt formation. However, mineralogical appearance as well as major and trace element composition of many leucosomes imply that leucosomes seldom represent frozen in-situ melts. They are better considered as remnants of the melt channel network, e.g. ways on which melts escaped from the system. Part III of the thesis describes how analyses of minerals from a specific rock type (granulite) can be used to determine partition coefficients between different minerals and between minerals and melt suitable for lower crustal conditions. The trace element analyses by laser ablation-ICP-MS show coherent distribution among the principal mineral phases independent of rock composition. REE contents in amphibole are about 3 times higher than REE contents in clinopyroxene from the same sample. This consistency has to be taken into consideration in models of lower crustal melting where amphibole is replaced by clinopyroxene in the course of melting. A lack of equilibrium is observed between matrix clinopyroxene / amphibole and garnet porphyroblasts which suggests a late stage growth of garnet and slow diffusion and equilibration of the REE during metamorphism. The data provide a first set of distribution coefficients of the transition metals (Sc, V, Cr, Ni) in the lower crust. In addition, analyses of ilmenite and apatite demonstrate the strong influence of accessory phases on trace element distribution. Apatite contains high amounts of REE and Sr while ilmenite incorporates about 20-30 times higher amounts of Nb and Ta than amphibole. Furthermore, trace element mineral analyses provide evidence for magmatic processes such as melt depletion, melt segregation, accumulation and fractionation as well as metasomatism having operated in this high-grade anatectic area.

Measurement of the differential cross section of tt pairs in pp collision at sqrt(s) = 7TeV with the ATLAS detector at the LHC

In this thesis three measurements of top-antitop differential cross section at an energy in the center of mass of 7 TeV will be shown, as a function of the transverse momentum, the mass and the rapidity of the top-antitop system. The analysis has been carried over a data sample of about 5/fb recorded with the ATLAS detector. The events have been selected with a cut based approach in the "one lepton plus jets" channel, where the lepton can be either an electron or a muon. The most relevant backgrounds (multi-jet QCD and W+jets) have been extracted using data driven methods; the others (Z+ jets, diboson and single top) have been simulated with Monte Carlo techniques. The final, background-subtracted, distributions have been corrected, using unfolding methods, for the detector and selection effects. At the end, the results have been compared with the theoretical predictions. The measurements are dominated by the systematic uncertainties and show no relevant deviation from the Standard Model predictions.

Markov Constraints for Generating Texts with Style

This thesis addresses the issue of generating texts in the style of an existing author, that also satisfy structural constraints imposed by the genre of the text. Although Markov processes are known to be suitable for representing style, they are difficult to control in order to satisfy non-local properties, such as structural constraints, that require long distance modeling. The framework of Constrained Markov Processes allows to precisely generate texts that are consistent with a corpus, while being controllable in terms of rhymes and meter. Controlled Markov processes consist in reformulating Markov processes in the context of constraint satisfaction. The thesis describes how to represent stylistic and structural properties in terms of constraints in this framework and how this approach can be used for the generation of lyrics in the style of 60 differents authors An evaluation of the desctibed method is provided by comparing it to both pure Markov and pure constraint-based approaches. Finally the thesis describes the implementation of an augmented text editor, called Perec. Perec is intended to improve creativity, by helping the user to write lyrics and poetry, exploiting the techniques presented so far.

Measurement of ttbar production differential cross section at \sqrt{s}=8 TeV at ATLAS

Top quark studies play an important role in the physics program of the Large Hadron Collider (LHC). The energy and luminosity reached allow the acquisition of a large amount of data especially in kinematic regions never studied before. In this thesis is presented the measurement of the ttbar production differential cross section on data collected by ATLAS in 2012 in proton proton collisions at \sqrt{s} = 8 TeV, corresponding to an integrated luminosity of 20.3 fb^{−1}. The measurement is performed for ttbar events in the semileptonic channel where the hadronically decaying top quark has a transverse momentum above 300 GeV. The hadronic top quark decay is reconstructed as a single large radius jet and identified using jet substructure properties. The final differential cross section result has been compared with several theoretical distributions obtaining a discrepancy of about the 25% between data and predictions, depending on the MC generator. Furthermore the kinematic distributions of the ttbar production process are very sensitive to the choice of the parton distribution function (PDF) set used in the simulations and could provide constraints on gluons PDF. In particular in this thesis is performed a systematic study on the PDF of the protons, varying several PDF sets and checking which one better describes the experimental distributions. The boosted techniques applied in this measurement will be fundamental in the next data taking at \sqrt{s}=13 TeV when will be produced a large amount of heavy particles with high momentum.

Glycogen-rich pleomorphic xanthoastrocytoma with clear-cell features: confirmatory report of a rare variant with implications for differential diagnosis

Central nervous system space-occupying lesions with clear-cell features encompass a nosologically heterogeneous array, ranging from reactive histiocytic proliferations to neuroepithelial or meningothelial neoplasms of various grades and to metastases. In the face of such differential diagnostic breadth, recognizing cytoplasmic lucency as part of the morphological spectrum of some low grade gliomas will directly have an impact on patient care. We describe a prevailing clear-cell change in an epileptogenic left temporal pleomorphic xanthoastrocytoma surgically resected from a 36-year-old man. Mostly subarachnoid and focally calcified, the tumor was composed of fascicles of moderately atypical spindle cells with optically lucent cytoplasm that tended to intermingle with a desmoplastic mesh of reticulin fibers. Immunohistochemically, coexpression of S100 protein, vimentin, GFAP, and CD34 was noted. Conversely, neither punctate staining for EMA nor positivity for CD68 was seen. Mitotic activity was absent, and the MIB1 labeling index was 2-3% on average. Diastase-sensitive PAS-positive granula indicated clear-cell change to proceed from glycogen storage. Electron microscopy showed tumor cell cytoplasm to be largely obliterated by non-lysosomal-bound pools of glycogen, while hardly any fat vacuole was encountered. Neither ependymal-derived organelles nor annular lamellae suggesting oligodendroglial differentiation were detected. The latter differential diagnosis was further invalidated by lack of codeletion of chromosomal regions 1p36 and 19q13 on molecular genetic testing. By significantly interfering with pattern recognition as an implicit approach in histopathology, clear-cell change in pleomorphic xanthoastrocytoma is likely to suspend its status as a "classic", and to prompt more deductive differential diagnostic strategies to exclude look-alikes, especially clear-cell ependymoma and oligodendroglioma.

Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: long-term follow up on IBCSG Trial IX

The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed.