Direct Determination of mechanical properties in shallow formations by (ultra) sonic methods

For several decades mechanical properties of shallow formations (soil) obtained by sonic to ultrasonic wave testing were reported to be greater than those based on mechanical tests. The present article relying on a statistical analysis of more than 300 tests shows that elastic moduli of the soil can indeed be obtained from (ultra)sonic tests and that they are identical to those resulting from mechanical tests.

Some solutions to obtain very efficient separations in isocratic and gradient modes using small particles size and ultra-high pressure.

The UHPLC strategy which combines sub-2 microm porous particles and ultra-high pressure (>1000 bar) was investigated considering very high resolution criteria in both isocratic and gradient modes, with mobile phase temperatures between 30 and 90 degrees C. In isocratic mode, experimental conditions to reach the maximal efficiency were determined using the kinetic plot representation for DeltaP(max)=1000 bar. It has been first confirmed that the molecular weight of the compounds (MW) was a critical parameter which should be considered in the construction of such curves. With a MW around 1000 g mol(-1), efficiencies as high as 300,000 plates could be theoretically attained using UHPLC at 30 degrees C. By limiting the column length to 450 mm, the maximal plate count was around 100,000. In gradient mode, the longest column does not provide the maximal peak capacity for a given analysis time in UHPLC. This was attributed to the fact that peak capacity is not only related to the plate number but also to column dead time. Therefore, a compromise should be found and a 150 mm column should be preferentially selected for gradient lengths up to 60 min at 30 degrees C, while the columns coupled in series (3x 150 mm) were attractive only for t(grad)>250 min. Compared to 30 degrees C, peak capacities were increased by about 20-30% for a constant gradient length at 90 degrees C and gradient time decreased by 2-fold for an identical peak capacity.

Detection of coronary stenoses with contrast enhanced, three-dimensional free breathing coronary MR angiography using the gadolinium-based intravascular contrast agent gadocoletic acid (B-22956).

PURPOSE: To determine the diagnostic value of the intravascular contrast agent gadocoletic acid (B-22956) in three-dimensional, free breathing coronary magnetic resonance angiography (MRA) for stenosis detection in patients with suspected or known coronary artery disease. METHODS: Eighteen patients underwent three-dimensional, free breathing coronary MRA of the left and right coronary system before and after intravenous application of a single dose of gadocoletic acid (B-22956) using three different dose regimens (group A 0.050 mmol/kg; group B 0.075 mmol/kg; group C 0.100 mmol/kg). Precontrast scanning followed a coronary MRA standard non-contrast T2 preparation/turbo-gradient echo sequence (T2Prep); for postcontrast scanning an inversion-recovery gradient echo sequence was used (real-time navigator correction for both scans). In pre- and postcontrast scans quantitative analysis of coronary MRA data was performed to determine the number of visible side branches, vessel length and vessel sharpness of each of the three coronary arteries (LAD, LCX, RCA). The number of assessable coronary artery segments was determined to calculate sensitivity and specificity for detection of stenosis > or = 50% on a segment-to-segment basis (16-segment-model) in pre- and postcontrast scans with x-ray coronary angiography as the standard of reference. RESULTS: Dose group B (0.075 mmol/kg) was preferable with regard to improvement of MR angiographic parameters: in postcontrast scans all MR angiographic parameters increased significantly except for the number of visible side branches of the left circumflex artery. In addition, assessability of coronary artery segments significantly improved postcontrast in this dose group (67 versus 88%, p < 0.01). Diagnostic performance (sensitivity, specificity, accuracy) was 83, 77 and 78% for precontrast and 86, 95 and 94% for postcontrast scans. CONCLUSIONS: The use of gadocoletic acid (B-22956) results in an improvement of MR angiographic parameters, asssessability of coronary segments and detection of coronary stenoses > or = 50%.

¿Som realment diferents els homes i les dones? Anàlisi de les diferències entre ambdós sexes en pacients amb malaltia vascular cerebral.

Es recullen les dades dels pacients amb ictus agut (isquèmic i hemorràgic) que ingressen al nostre servei i es comparen les dades epidemiològiques, clíniques i de pronòstic de dones i homes. En l'anàlisi comparatiu s’objectiven diferències en quant als factors de risc entre ambdós sexes. I es troben factors independents de mal pronòstic en els pacients amb un ictus isquèmic: l'antecedent de cardiopatia isquèmica, l’escala de rankin previ i l'escala canadenca a l'ingrés. En l'anàlisi de regressió logística es troben factors independents de mal pronòstic en els pacients amb una hemorràgia cerebral l'edat i l'escala canadenca a l'ingrés.

Design of Novel Frequency Generation Circuit with Application to Ultra-Wideband Distributed Oscillators

Given the urgence of a new paradigm in wireless digital trasmission which should allow for higher bit rate, lower latency and tigher delay constaints, it has been proposed to investigate the fundamental building blocks that at the circuital/device level, will boost the change towards a more efficient network architecture, with high capacity, higher bandwidth and a more satisfactory end user experience. At the core of each transciever, there are inherently analog devices capable of providing the carrier signal, the oscillators. It is strongly believed that many limitations in today's communication protocols, could be relieved by permitting high carrier frequency radio transmission, and having some degree of reconfigurability. This led us to studying distributed oscillator architectures which work in the microwave range and possess wideband tuning capability. As microvave oscillators are essentially nonlinear devices, a full nonlinear analyis, synthesis, and optimization had to be considered for their implementation. Consequently, all the most used nonlinear numerical techniques in commercial EDA software had been reviewed. An application of all the aforementioned techniques has been shown, considering a systems of three coupled oscillator ("triple push" oscillator) in which the stability of the various oscillating modes has been studied. Provided that a certain phase distribution is maintained among the oscillating elements, this topology permits a rise in the output power of the third harmonic; nevertheless due to circuit simmetry, "unwanted" oscillating modes coexist with the intenteded one. Starting with the necessary background on distributed amplification and distributed oscillator theory, the design of a four stage reverse mode distributed voltage controlled oscillator (DVCO) using lumped elments has been presented. All the design steps have been reported and for the first time a method for an optimized design with reduced variations in the output power has been presented. Ongoing work is devoted to model a wideband DVCO and to implement a frequency divider.

Targetting of the ventro-intermediate nucleus using ultra-high field (7T) MRI for gamma knife surgery purposes: A pilot in vivo study on healthy subjects.

INTRODUCTION: Gamma Knife surgery (GKS) is a non-invasive neurosurgical stereotactic procedure, increasingly used as an alternative to open functional procedures. This includes targeting of the ventro-intermediate nucleus of the thalamus (e.g. Vim) for tremor. We currently perform an indirect targeting, as the Vim is not visible on current 3Tesla MRI acquisitions. Our objective was to enhance anatomic imaging (aiming at refining the precision of anatomic target selection by direct visualisation) in patients treated for tremor with Vim GKS, by using high field 7T MRI. MATERIALS AND METHODSH: Five young healthy subjects were scanned on 3 (T1-w and diffusion tensor imaging) and 7T (high-resolution susceptibility weighted images (SWI)) MRI in Lausanne. All images were further integrated for the first time into the Gamma Plan Software(®) (Elekta Instruments, AB, Sweden) and co-registered (with T1 was a reference). A simulation of targeting of the Vim was done using various methods on the 3T images. Furthermore, a correlation with the position of the found target with the 7T SWI was performed. The atlas of Morel et al. (Zurich, CH) was used to confirm the findings on a detailed analysis inside/outside the Gamma Plan. RESULTS: The use of SWI provided us with a superior resolution and an improved image contrast within the basal ganglia. This allowed visualization and direct delineation of some subgroups of thalamic nuclei in vivo, including the Vim. The position of the target, as assessed on 3T, perfectly matched with the supposed one of the Vim on the SWI. Furthermore, a 3-dimensional model of the Vim-target area was created on the basis of the obtained images. CONCLUSION: This is the first report of the integration of SWI high field MRI into the LGP, aiming at the improvement of targeting validation of the Vim in tremor. The anatomical correlation between the direct visualization on 7T and the current targeting methods on 3T (e.g. quadrilatere of Guyot, histological atlases) seems to show a very good anatomical matching. Further studies are needed to validate this technique, both by improving the accuracy of the targeting of the Vim (potentially also other thalamic nuclei) and to perform clinical assessment.

Ultra-high pressure liquid chromatography-mass spectrometry for plant metabolomics: a systematic comparison of high-resolution quadrupole-time-of-flight and single stage Orbitrap mass spectrometers.

The response of Arabidopsis to stress caused by mechanical wounding was chosen as a model to compare the performances of high resolution quadrupole-time-of-flight (Q-TOF) and single stage Orbitrap (Exactive Plus) mass spectrometers in untargeted metabolomics. Both instruments were coupled to ultra-high pressure liquid chromatography (UHPLC) systems set under identical conditions. The experiment was divided in two steps: the first analyses involved sixteen unwounded plants, half of which were spiked with pure standards that are not present in Arabidopsis. The second analyses compared the metabolomes of mechanically wounded plants to unwounded plants. Data from both systems were extracted using the same feature detection software and submitted to unsupervised and supervised multivariate analysis methods. Both mass spectrometers were compared in terms of number and identity of detected features, capacity to discriminate between samples, repeatability and sensitivity. Although analytical variability was lower for the UHPLC-Q-TOF, generally the results for the two detectors were quite similar, both of them proving to be highly efficient at detecting even subtle differences between plant groups. Overall, sensitivity was found to be comparable, although the Exactive Plus Orbitrap provided slightly lower detection limits for specific compounds. Finally, to evaluate the potential of the two mass spectrometers for the identification of unknown markers, mass and spectral accuracies were calculated on selected identified compounds. While both instruments showed excellent mass accuracy (<2.5ppm for all measured compounds), better spectral accuracy was recorded on the Q-TOF. Taken together, our results demonstrate that comparable performances can be obtained at acquisition frequencies compatible with UHPLC on Q-TOF and Exactive Plus MS, which may thus be equivalently used for plant metabolomics.

Isolation of genetic mutation leading to abnormal phenotype in human through ultra-high-throughput sequencing (UHTS)

The introduction of Next Generation Sequencing (NGS) facilitated the task of localizing DNA variation and identifying the genetic cause of yet unsolved Mendelian disorders. Using Whole Exome Capture method and NGS, we identified the causative genetic aberration responsible for a number of monogenic disorders previously undetermined. Due to the novelty of the NGS method we benchmarked different algorithms to assess their merits and defects. This allowed us to establish a pipeline that we successfully used to pinpoint genes responsible for a form of West's syndrome, a Complex Intellectual Disability syndrome associated with patellar dislocation and celiac disease, and correcting some erroneous molecular diagnosis of Alport's syndrome in a Saudi Arabian family.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. II: Confirmatory analysis.

For doping control, analyses of samples are generally achieved in two steps: a rapid screening and, in the case of a positive result, a confirmatory analysis. A two-step methodology based on ultra-high-pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was developed to screen and confirm 103 doping agents from various classes (e.g., beta-blockers, stimulants, diuretics, and narcotics). The screening method was presented in a previous article as part I (i.e., Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry. Part I: screening analysis). For the confirmatory method, basic, neutral and acidic compounds were extracted by a dedicated solid-phase extraction (SPE) in a 96-well plate format and detected by MS in the tandem mode to obtain precursor and characteristic product ions. The mass accuracy and the elemental composition of precursor and product ions were used for compound identification. After validation including matrix effect determination, the method was considered reliable to confirm suspect results without ambiguity according to the positivity criteria established by the World Anti-Doping Agency (WADA). Moreover, an isocratic method was developed to separate ephedrine from its isomer pseudoephedrine and cathine from phenylpropanolamine in a single run, what allowed their direct quantification in urine.

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.

Laser-ultraviolet-A induced ultra weak photon emission in human skin cells: A biophotonic comparison between keratinocytes and fibroblasts.

Photons participate in many atomic and molecular interactions and processes. Recent biophysical research has discovered an ultraweak radiation in biological tissues. It is now recognized that plants, animal and human cells emit this very weak biophotonic emission which can be readily measured with a sensitive photomultiplier system. UVA laser induced biophotonic emission of cultured cells was used in this report with the intention to detect biophysical changes between young and adult fibroblasts as well as between fibroblasts and keratinocytes. With suspension densities ranging from 1-8 x 106 cells/ml, it was evident that an increase of the UVA-laser-light induced photon emission intensity could be observed in young as well as adult fibroblastic cells. By the use of this method to determine ultraweak light emission, photons in cell suspensions in low volumes (100 microl) could be detected, in contrast to previous procedures using quantities up to 10 ml. Moreover, the analysis has been further refined by turning off the photomultiplier system electronically during irradiation leading to the first measurements of induced light emission in the cells after less than 10 micros instead of more than 100 milliseconds. These significant changes lead to an improvement factor up to 106 in comparison to classical detection procedures. In addition, different skin cells as fibroblasts and keratinocytes stemming from the same donor were measured using this new highly sensitive method in order to find new biophysical insight of light pathways. This is important in view to develop new strategies in biophotonics especially for use in alternative therapies.

Ultra-fast recovery from right neglect after 'awake surgery' for slow-growing tumor invading the left parietal area

It is now possible to perform resections of slow-growing tumors in awake patients. Using direct electrical stimulation, real-time functional mapping of the brain can be used to prevent the resection of essential areas near the tumor. Simple clinical observations of patients with a resection of slow-growing tumors have demonstrated substantial recovery within a few days of such 'awake surgery'. The aim of this study was to investigate the kinetics of recovery following the resection of slow-growing tumors invading the left parietal area and to focus mainly on its rapidity. Two patients were assessed by standard line bisection tests and compared with eight healthy individuals. Independently of the pure nature of the symptoms, we report that the patients rapidly and substantially recovered from pronounced right neglect. They were tested 48 hours after the surgery and the recovery was significant for both patients after less than 4 hours. Strikingly, for one patient, recovery was ultra fast and substantial in the first practice session within less than 7 minutes: it occurred without verbal feedback and was substantially retained during the following testing session. Its rapidity suggests a process of unmasking redundant networks. With the slow growth of the lesion, the contralesional hemisphere is probably progressively prepared for rapid unmasking of homologue networks. These results have major clinical implications. For patients with an invading left-side tumor, it is now clear that line bisections are required before, during, and after awake surgery to: plan the surgery, control the quality of the resection, and also optimize the rehabilitation of the patient

Growth and characterization of CoO ultra thin films

In this report we present the growth process of the cobalt oxide system using reactive electron beam deposition. In that technique, a target of metallic cobalt is evaporated and its atoms are in-flight oxidized in an oxygen rich reactive atmosphere before reaching the surface of the substrate. With a trial and error procedure the deposition parameters have been optimized to obtain the correct stoichiometry and crystalline phase. The evaporation conditions to achieve the correct cobalt oxide salt rock structure, when evaporating over amorphous silicon nitride, are: 525 K of substrate temperature, 2.5·10-4 mbar of oxygen partial pressure and 1 Å/s of evaporation rate. Once the parameters were optimized a set of ultra thin film ranging from samples of 1 nm of nominal thickness to 20nm thick and bulk samples were grown. With the aim to characterize the samples and study their microstructure and morphology, X-ray diffraction, transmission electron microscopy, electron diffraction, energy dispersive X-ray spectroscopy and quasi-adiabatic nanocalorimetry techniques are utilised. The final results show a size dependent effect of the antiferromagnetic transition. Its Néel temperature becomes depressed as the size of the grains forming the layer decreases.

Ultra high throughput sequencing in human DNA variation detection: a comparative study on the NDUFA3-PRPF31 region.

BACKGROUND: Ultra high throughput sequencing (UHTS) technologies find an important application in targeted resequencing of candidate genes or of genomic intervals from genetic association studies. Despite the extraordinary power of these new methods, they are still rarely used in routine analysis of human genomic variants, in part because of the absence of specific standard procedures. The aim of this work is to provide human molecular geneticists with a tool to evaluate the best UHTS methodology for efficiently detecting DNA changes, from common SNPs to rare mutations. METHODOLOGY/PRINCIPAL FINDINGS: We tested the three most widespread UHTS platforms (Roche/454 GS FLX Titanium, Illumina/Solexa Genome Analyzer II and Applied Biosystems/SOLiD System 3) on a well-studied region of the human genome containing many polymorphisms and a very rare heterozygous mutation located within an intronic repetitive DNA element. We identify the qualities and the limitations of each platform and describe some peculiarities of UHTS in resequencing projects. CONCLUSIONS/SIGNIFICANCE: When appropriate filtering and mapping procedures are applied UHTS technology can be safely and efficiently used as a tool for targeted human DNA variations detection. Unless particular and platform-dependent characteristics are needed for specific projects, the most relevant parameter to consider in mainstream human genome resequencing procedures is the cost per sequenced base-pair associated to each machine.