Ultraconserved elements in the human genome

There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development. Along with more than 5000 sequences of over 100 bp that are absolutely conserved among the three sequenced mammals, these represent a class of genetic elements whose functions and evolutionary origins are yet to be determined, but which are more highly conserved between these species than are proteins and appear to be essential for the ontogeny of mammals and other vertebrates.

The application of fibre Bragg grating networks as strain sensors and as phased array antenna true time delay elements

The fabrication of in-fibre Bragg gratings, and the application of arrays of such gratings as strain sensors and as true time delay elements for the control of phased array antennas is reported. Chirped period Bragg gratings were produced using the fibre deformation fabrication technique, with chirps of between 2.9nm and 17.3nm achieved. Arrays of 5mm and 2mm long uniform period Bragg gratings were fabricated using the inscription method, for use as true time delay elements,dissimilar wavefronts and their spectral characteristics recorded. The uniform period grating arrays were used to create minimum time delays of 9.09ps, 19.02ps and 31ps; making them suitable for controlling phased array antennas operating at RF frequencies of up to 3GHz, with 10° phase resolution. Four 4mm long chirped gratings were produced using the dissimilar wavefronts fabrication method, having chirps of 7nm, 12nm, 20nm and 30nm, and were used to create time delays of between 0.3ps and 59ps. Hence they are suitable for controlling phased array antennas at RF frequencies of up to 48GHz. The application of in fibre Bragg gratings as strain sensors within smart structure materials was investigated, with their sensitivity to applied strain and compression measured for both embedded and surface mounted uniform period and fibre Fabry-Perot filter gratings. A fibre Bragg grating sensor demultiplexing scheme based on a liquid crystal filled Fabry-Perot etalon tuneable transmission filter was proposed, successfully constructed and fully characterised. Three characteristics of the LCFP etalon were found to pose operational limitations to its application in a Bragg grating sensor system; most significantly, the resonance peak wavelength was highly (-2,77nm/°C) temperature dependent. Several methods for minimising this temperature sensitivity were investigated, but enjoyed only limited success. It was therefore concluded that this type (E7 filled) of LCFP etalon is unsuitable for use as a Bragg grating sensor demultiplexing element.

From cardinal spline wavelet bases to highly coherent dictionaries

Wavelet families arise by scaling and translations of a prototype function, called the mother wavelet. The construction of wavelet bases for cardinal spline spaces is generally carried out within the multi-resolution analysis scheme. Thus, the usual way of increasing the dimension of the multi-resolution subspaces is by augmenting the scaling factor. We show here that, when working on a compact interval, the identical effect can be achieved without changing the wavelet scale but reducing the translation parameter. By such a procedure we generate a redundant frame, called a dictionary, spanning the same spaces as a wavelet basis but with wavelets of broader support. We characterize the correlation of the dictionary elements by measuring their 'coherence' and produce examples illustrating the relevance of highly coherent dictionaries to problems of sparse signal representation.

Comparison of frequency symmetric signal generation from a BPSK input using fiber and semiconductor-based nonlinear elements

This letter compares two nonlinear media for simultaneous carrier recovery and generation of frequency symmetric signals from a 42.7-Gb/s nonreturn-to-zero binary phase-shift-keyed input by exploiting four-wave mixing in a semiconductor optical amplifier and a highly nonlinear optical fiber for use in a phase-sensitive amplifier.

Highly sensitive liquid-level sensor based on dual-wavelength double-ring fiber laser assisted by beat frequency interrogation

A highly sensitive liquid-level sensor based on dual-wavelength single-longitudinal-mode fiber laser is proposed and demonstrated. The laser is formed by exploiting two parallel arranged phase-shift fiber Bragg gratings (ps-FBGs), acting as ultra-narrow bandwidth filters, into a doublering resonators. By beating the dual-wavelength lasing output, a stable microwave signal with frequency stability better than 5 MHz is obtained. The generated beat frequency varies with the change of dual-wavelength spacing. Based on this characteristic, with one ps-FBG serving as the sensing element and the other one acting as the reference element, a highly sensitive liquid level sensor is realized by monitoring the beat frequency shift of the laser. The sensor head is directly bonded to a float which can transfer buoyancy into axial strain on the fiber without introducing other elastic elements. The experimental results show that an ultra-high liquidlevel sensitivity of 2.12 × 107 MHz/m within the measurement range of 1.5 mm is achieved. The sensor presents multiple merits including ultra-high sensitivity, thermal insensitive, good reliability and stability. © 2012 Optical Society of America.

Thermodynamic description and phase transformation of highly symmetrical monoatomic structures

Based on theoretical considerations an explanation for the temperature dependence of the thermal expansion and the bulk modulus is proposed. A new equation state is also derived. Additionally a physical explanation for the latent heat of fusion is presented. These theoretical predictions are tested against experiments on highly symmetrical monatomic structures. ^ The volume is not an independent variable and must be broken down into its fundamental components when the relationships to the pressure and temperature are defined. Using zero pressure and temperature reference frame, the initial parameters, volume at zero pressure and temperature[V°], bulk modulus at zero temperature [K°] and volume coefficient of thermal expansion at zero pressure[α°] are defined. ^ The new derived EoS is tested against the experiments on perovskite and epsilon iron. The Root-mean-square-deviations (RMSD) of the residuals of the molar volume, pressure, and temperature are in the range of the uncertainty of the experiments. ^ Separating the experiments into 200 K ranges, the new EoS was compared to the most widely used finite strain, interatomic potential, and empirical isothermal EoSs such as the Burch-Murnaghan, the Vinet, and the Roy-Roy respectively. Correlation coefficients, RMSD's of the residuals, and Akaike Information Criteria were used for evaluating the fitting. Based on these fitting parameters, the new p-V-T EoS is superior in every temperature range relative to the investigated conventional isothermal EoS. ^ The new EoS for epsilon iron reproduces the preliminary-reference earth-model (PREM) densities at 6100-7400 K indicating that the presence of light elements might not be necessary to explain the Earth's inner core densities. ^ It is suggested that the latent heat of fusion supplies the energy required for overcoming on the viscous drag resistance of the atoms. The calculated energies for melts formed from highly symmetrical packing arrangements correlate very well with experimentally determined latent heat values. ^ The optical investigation of carhonado-diamond is also part of the dissertation. The collected first complete infrared FTIR absorption spectra for carhonado-diamond confirm the interstellar origin for the most enigmatic diamonds known as carbonado. ^

Termination II record, stable isotopes and trace elements of Stagamite MF-3 from Schafsloch Cave

The timing and nature of the penultimate deglaciation, also known as Termination II (T-II), is subject of controversial discussions due to the scarcity of precisely-dated palaeoclimate records. Here we present a new precisely-dated and highly-resolved multi-proxy stalagmite record covering T-II from the high alpine Schafsloch Cave in Switzerland, an area where climate is governed by the North Atlantic. The inception of stalagmite growth at 137.4 ± 1.4 kyr before present (BP) indicates the presence of drip water and cave air temperatures of above 0 °C, and is related to a climate-induced change in the thermal state (from cold-to warm-based) of the glacier above the cave. The cessation of stalagmite growth between 133.1 ± 0.7 and 131.9 ± 0.6 kyr BP is most likely related to distinct drop in temperature associated with Heinrich stadial 11. The resumption of stalagmite growth at 131.9 ± 0.6 kyr BP is accompanied by an abrupt increase in temperature and precipitation as indicated by distinct shifts in the oxygen and carbon isotopic composition as well as in trace element concentrations. The mid-point of T-II is around 131.8 ± 0.6 kyr BP in the Schafsloch Cave record is significantly earlier compared to the age of 129.1 ± 0.1 kyr BP in the Sanbao Cave record from China. The different ages between both records can be best explained by the competing effects of insolation and glacial boundary forcing on seasonality and snow cover extent in Eurasia.

Characterization of a Full-Length TTP Family Member Association with RNA Sequence Elements

Post-transcriptional regulation of cytoplasmic mRNAs is an efficient mechanism of regulating the amounts of active protein within a eukaryotic cell. RNA sequence elements located in the untranslated regions of mRNAs can influence transcript degradation or translation through associations with RNA-binding proteins. Tristetraprolin (TTP) is the best known member of a family of CCCH zinc finger proteins that targets adenosine-uridine rich element (ARE) binding sites in the 3’ untranslated regions (UTRs) of mRNAs, promoting transcript deadenylation through the recruitment of deadenylases. More specifically, TTP has been shown to bind AREs located in the 3’-UTRs of transcripts with known roles in the inflammatory response. The mRNA-binding region of the protein is the highly conserved CCCH tandem zinc finger (TZF) domain. The synthetic TTP TZF domain has been shown to bind with high affinity to the 13-mer sequence of UUUUAUUUAUUUU. However, the binding affinities of full-length TTP family members to the same sequence and its variants are unknown. Furthermore, the distance needed between two overlapping or neighboring UUAUUUAUU 9-mers for tandem binding events of a full-length TTP family member to a target transcript has not been explored. To address these questions, we recombinantly expressed and purified the full-length C. albicans TTP family member Zfs1. Using full-length Zfs1, tagged at the N-terminus with maltose binding protein (MBP), we determined the binding affinities of the protein to the optimal TTP binding sequence, UUAUUUAUU. Fluorescence anisotropy experiments determined that the binding affinities of MBP-Zfs1 to non-canonical AREs were influenced by ionic buffer strength, suggesting that transcript selectivity may be affected by intracellular conditions. Furthermore, electrophoretic mobility shift assays (EMSAs) revealed that separation of two core AUUUA sequences by two uridines is sufficient for tandem binding of MBP-Zfs1. Finally, we found evidence for tandem binding of MBP-Zfs1 to a 27-base RNA oligonucleotide containing only a single ARE-binding site, and showed that this was concentration and RNA length dependent; this phenomenon had not been seen previously. These data suggest that the association of the TTP TZF domain and the TZF domains of other species, to ARE-binding sites is highly conserved. Domains outside of the TZF domain may mediate transcript selectivity in changing cellular conditions, and promote protein-RNA interactions not associated with the ARE-binding TZF domain.

In summary, the evidence presented here suggests that Zfs1-mediated decay of mRNA targets may require additional interactions, in addition to ARE-TZF domain associations, to promote transcript destabilization and degradation. These studies further our understanding of post-transcriptional steps in gene regulation.

Major and trace elements and Nd and Sr isotope geochemistry of basalts at DSDP Leg 74 Holes

Basement intersected in Holes 525A, 528, and 527 on the Walvis Ridge consists of submarine basalt flows and pillows with minor intercalated sediments. These holes are situated on the crest and mid- and lower NW flank of a NNW-SSE-trending ridge block which would have closely paralleled the paleo mid-ocean ridge. The basalts were erupted approximately 70 Ma, a date consistent with formation at the paleo mid-ocean ridge. The basalt types vary from aphyric quartz tholeiites on the Ridge crest to highly Plagioclase phyric olivine tholeiites on the flank. These show systematic differences in incompatible trace element and isotopic composition, and many element and isotope ratio pairs form systematic trends with the Ridge crest basalts at one end and the highly phyric Ridge flank basalts at the other. The low 143Nd/144Nd (0.51238) and high 87Sr/86Sr (0.70512) ratios of the Ridge crest basalts suggest derivation from an old Nd/Sm and Rb/Sr enriched mantle source. This isotopic signature is similar to that of alkaline basalts on Tristan da Cunha but offset by somewhat lower 143Nd/144Nd values. The isotopic ratio trends may be extrapolated beyond the Ridge flank basalts (which have 143Nd/144Nd of 0.51270 and 87Sr/86Sr of 0.70417) in the direction of typical MORB compositions. These isotopic correlations are equally consistent with mixing of depleted and enriched end-member melts or partial melting of an inhomogeneous, variably enriched mantle source. However, observed Zr-Ba-Nb-Y interelement relationships are inconsistent with any simple two-component model of magma mixing or partial melting. They also preclude extensive involvement of depleted (N-type) MORB material or its mantle sources in the petrogenesis of Walvis Ridge basalts.

Seawater carbonate chemistry and conditions of Mytilus edulis extracellular body fluids and shell composition in a pH-treatment experiment: Acid-base status, trace elements and delta11B, 2012

Mytilus edulis were cultured for 3 months under six different seawater pCO2 levels ranging from 380 to 4000 µatm. Specimen were taken from Kiel Fjord (Western Baltic Sea, Germany) which is a habitat with high and variable seawater pCO2 and related shifts in carbonate system speciation (e.g., low pH and low CaCO3 saturation state). Hemolymph (HL) and extrapallial fluid (EPF) samples were analyzed for pH and total dissolved inorganic carbon (CT) to calculate pCO2 and [HCO3]. A second experiment was conducted for 2 months with three different pCO2 levels (380, 1400 and 4000 µatm). Boron isotopes (delta11B) were investigated by LA-MC-ICP-MS (Laser Ablation-Multicollector-Inductively Coupled Plasma-Mass Spectrometry) in shell portions precipitated during experimental treatment time. Additionally, elemental ratios (B/Ca, Mg/Ca and Sr/Ca) in the EPF of specimen from the second experiment were measured via ICP-OES (Inductively Coupled Plasma-Optical Emission Spectrometry). Extracellular pH was not significantly different in HL and EPF but systematically lower than ambient water pH. This is due to high extracellular pCO2 values, a prerequisite for metabolic CO2 excretion. No accumulation of extracellular [HCO3] was measured. Elemental ratios (B/Ca, Mg/Ca and Sr/Ca) in the EPF increased slightly with pH which is in accordance with increasing growth and calcification rates at higher seawater pH values. Boron isotope ratios were highly variable between different individuals but also within single shells. This corresponds to a high individual variability in fluid B/Ca ratios and may be due to high boron concentrations in the organic parts of the shell. The mean delta11B value shows no trend with pH but appears to represent internal pH (EPF) rather than ambient water pH.

Volcanic processes and human exposure as elements to build a risk model for Volcan de Fuego, Guatemala

The activity of Fuego volcano during the 1999 - 2013 eruptive episode is studied through field, remote sensing and observatory records. Mapping of the deposits allows quantifying the erupted volumes and areas affected by the largest eruptions during this period. A wide range of volcanic processes results in a diversity of products and associated deposits, including minor airfall tephra, rockfall avalanches, lava flows, and pyroclastic flows. The activity can be characterized by long term, low level background activity, and sporadic larger explosive eruptions. Although the background activity erupts lava and ash at a low rate (~ 0.1 m3/s), the persistence of such activity over time results in a significant contribution (~ 30%) to the eruption budget during the studied period. Larger eruptions produced the majority of the volume of products during the studied period, mainly during three large events (May 21, 1999, June 29, 2003, and September 13, 2012), mostly in the form of pyroclastic flows. A total volume of ~ 1.4 x 108 m3 was estimated from the mapped deposits and the estimated background eruption rate. Posterior remobilization of pyroclastic flow material by stream erosion in the highly confined Barranca channels leads to lahar generation, either by normal rainfall, or by extreme rainfall events. A reassessment of the types of products and volumes erupted during the decade of 1970's allows comparing the activity happening since 1999 with the older activity, and suggests that many of the eruptive phenomena at Fuego may have similar mechanisms, despite the differences in scale between. The deposits of large pyroclastic flows erupted during the 1970's are remarkably similar in appearance to the deposit of pyroclastic flows from the 1999 - 2013 period, despite their much larger volume; this is also the case for prehistoric eruptions. Radiocarbon dating of pyroclastic flow deposits suggests that Fuego has produced large eruptions many times during the last ~ 2 ka, including larger eruptions during the last 500 years, which has important hazard implications. A survey was conducted among the local residents living near to the volcano, about their expectations of possible future crises. The results show that people are aware of the risk they could face in case of a large eruption, and therefore they are willing to evacuate in such case. However, their decision to evacuate may also be influenced by the conditions in which the evacuation could take place. If the evacuation represents a potential loss of their livelihood or property they will be more hesitant to leave their villages during a large eruption. The prospect of facing hardship conditions during the evacuation and in the shelters may further cause reluctance to evacuate. A short discussion on some of the issues regarding risk assessment and management through an early warning system is presented in the last chapter.

A Highly Improved Method For Sensitive Determination Of Amitriptyline In Pharmaceutical Formulations Using An Unmodified Carbon Nanotube Electrode In The Presence Of Sulfuric Acid.

The present paper describes a novel, simple and reliable differential pulse voltammetric method for determining amitriptyline (AMT) in pharmaceutical formulations. It has been described for many authors that this antidepressant is electrochemically inactive at carbon electrodes. However, the procedure proposed herein consisted in electrochemically oxidizing AMT at an unmodified carbon nanotube paste electrode in the presence of 0.1 mol L(-1) sulfuric acid used as electrolyte. At such concentration, the acid facilitated the AMT electroxidation through one-electron transfer at 1.33 V vs. Ag/AgCl, as observed by the augmentation of peak current. Concerning optimized conditions (modulation time 5 ms, scan rate 90 mV s(-1), and pulse amplitude 120 mV) a linear calibration curve was constructed in the range of 0.0-30.0 μmol L(-1), with a correlation coefficient of 0.9991 and a limit of detection of 1.61 μmol L(-1). The procedure was successfully validated for intra- and inter-day precision and accuracy. Moreover, its feasibility was assessed through analysis of commercial pharmaceutical formulations and it has been compared to the UV-vis spectrophotometric method used as standard analytical technique recommended by the Brazilian Pharmacopoeia.

Micromorphology Of The Dental Pulp Is Highly Preserved In Cancer Patients Who Underwent Head And Neck Radiotherapy.

Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy. Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed. The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples. Direct effects of radiotherapy are not able to generate morphologic changes in the microvasculature, innervation, and extracellular matrix components of the dental pulp in head and neck cancer patients.

Chemical Immobilization Of Crosslinked Polymeric Ionic Liquids On Nitinol Wires Produces Highly Robust Sorbent Coatings For Solid-phase Microextraction.

Super elastic nitinol (NiTi) wires were exploited as highly robust supports for three distinct crosslinked polymeric ionic liquid (PIL)-based coatings in solid-phase microextraction (SPME). The oxidation of NiTi wires in a boiling (30%w/w) H2O2 solution and subsequent derivatization in vinyltrimethoxysilane (VTMS) allowed for vinyl moieties to be appended to the surface of the support. UV-initiated on-fiber copolymerization of the vinyl-substituted NiTi support with monocationic ionic liquid (IL) monomers and dicationic IL crosslinkers produced a crosslinked PIL-based network that was covalently attached to the NiTi wire. This alteration alleviated receding of the coating from the support, which was observed for an analogous crosslinked PIL applied on unmodified NiTi wires. A series of demanding extraction conditions, including extreme pH, pre-exposure to pure organic solvents, and high temperatures, were applied to investigate the versatility and robustness of the fibers. Acceptable precision of the model analytes was obtained for all fibers under these conditions. Method validation by examining the relative recovery of a homologous group of phthalate esters (PAEs) was performed in drip-brewed coffee (maintained at 60 °C) by direct immersion SPME. Acceptable recoveries were obtained for most PAEs in the part-per-billion level, even in this exceedingly harsh and complex matrix.

The Characterization Of The Endoglucanase Cel12a From Gloeophyllum Trabeum Reveals An Enzyme Highly Active On β-glucan.

The basidiomycete fungus Gloeophyllum trabeum causes a typical brown rot and is known to use reactive oxygen species in the degradation of cellulose. The extracellular Cel12A is one of the few endo-1,4-β-glucanase produced by G. trabeum. Here we cloned cel12A and heterologously expressed it in Aspergillus niger. The identity of the resulting recombinant protein was confirmed by mass spectrometry. We used the purified GtCel12A to determine its substrate specificity and basic biochemical properties. The G. trabeum Cel12A showed highest activity on β-glucan, followed by lichenan, carboxymethylcellulose, phosphoric acid swollen cellulose, microcrystalline cellulose, and filter paper. The optimal pH and temperature for enzymatic activity were, respectively, 4.5 and 50 °C on β-glucan. Under these conditions specific activity was 239.2 ± 9.1 U mg(-1) and the half-life of the enzyme was 84.6 ± 3.5 hours. Thermofluor studies revealed that the enzyme was most thermal stable at pH 3. Using β-glucan as a substrate, the Km was 3.2 ± 0.5 mg mL(-1) and the Vmax was 0.41 ± 0.02 µmol min(-1). Analysis of the effects of GtCel12A on oat spelt and filter paper by scanning electron microscopy revealed the morphological changes taking place during the process.