A short in-frame deletion in NTRK1 tyrosine kinase domain caused by a novel splice site mutation in a patient with congenital insensitivity to pain with anhidrosis

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease characterized by the lack of reaction to noxious stimuli and anhidrosis. It is caused by mutations in the NTRK1 gene, which encodes the high affinity tyrosine kinase receptor I for Neurotrophic Growth Factor (NGF). -- Case Presentation: We present the case of a female patient diagnosed with CIPA at the age of 8 months. The patient is currently 6 years old and her psychomotor development conforms to her age (RMN, SPECT and psychological study are in the range of normality). PCR amplification of DNA, followed by direct sequencing, was used to investigate the presence of NTRK1 gene mutations. Reverse transcriptase (RT)-PCR amplification of RNA, followed by cloning and sequencing of isolated RT-PCR products was used to characterize the effect of the mutations on NTRK1 mRNA splicing. The clinical diagnosis of CIPA was confirmed by the detection of two splice-site mutations in NTRK1, revealing that the patient was a compound heterozygote at this gene. One of these alterations, c.574+1G > A, is located at the splice donor site of intron 5. We also found a second mutation, c.2206-2 A > G, not previously reported in the literature, which is located at the splice acceptor site of intron 16. Each parent was confirmed to be a carrier for one of the mutations by DNA sequencing analysis. It has been proposed that the c.574+1G > A mutation would cause exon 5 skipping during NTRK1 mRNA splicing. We could confirm this prediction and, more importantly, we provide evidence that the novel c.2206-2A > G mutation also disrupts normal NTRK1 splicing, leading to the use of an alternative splice acceptor site within exon 17. As a consequence, this mutation would result in the production of a mutant NTRK1 protein with a seven aminoacid in-frame deletion in its tyrosine kinase domain. --Conclusions: We present the first description of a CIPA-associated NTRK1 mutation causing a short interstitial deletion in the tyrosine kinase domain of the receptor. The possible phenotypical implications of this mutation are discussed.

A short survey of the environment at the dumping site for Santa Cruz Harbor dredging and A study of seaward dipping internal structures in marine ripple marks at Whaler's Cove, California. Annual report, Part 4, August 1972

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Short communication: Rapid separation of cis9, trans11- and trans7,cis9-18:2 (CLA) isomers from ruminant tissue using a 30 m SLB-IL111 ionic column

[EN]Rumenic acid (cis9,trans11-18:2) is the main natural isomer of conjugated linoleic acid (CLA). Rumenic acid has many purported health benefits, but effects of most other CLA isomers are unknown. Typically trans7,cis9-18:2 is the second most abundant CLA isomer, but it co-elutes with rumenic acid on conventional polar gas chromatography (GC) columns, requiring complimentary analysis with silver-ion high performance liquid chromatography (Ag(+)-HPLC). Herein we report a rapid method for analyzing rumenic acid and trans7,cis9-18:2 using a 30 m ionic-liquid GC column. Optimal resolution of the two CLA isomers was at 145 degrees C and analysis of backfat from barley-fed cattle compared well with GC/Ag(+)-HPLC (y =0.978x - 0.031, r =0.985, P <0.001).

Short-Term Nonlinear Response of Tension Leg Platform in Random Sea Waves

Most of the existing mathematical models for analyzing the dynamic response of TLP are based on explicit or implicit assumptions that motions (translations and rotations) are small magnitude. However, when TLP works in severe adverse conditions, the a priori assumption on small displacements may be inadequate. In such situation, the motions should be regarded as finite magnitude. This paper will study stochastic nonlinear dynamic responses of TLP with finite displacements in random waves. The nonlinearities considered are: large amplitude motions, coupling the six degrees-of-freedom, instantaneous position, instantaneous wet surface, free surface effects and viscous drag force. The nonlinear dynamic responses are calculated by using numerical integration procedure in the time domain. After the time histories of the dynamic responses are obtained, we carry out cycle counting of the stress histories of the tethers with rain-flow counting method to get the stress range distribution.

Two-phase Flow in Fuel Cells in Short-term Microgravity Condition

A visual observation of liquid-gas two-phase flow in anode channels of a direct methanol proton exchange membrane fuel cells in microgravity has been carried out in a drop tower. The anode flow bed consisted of 2 manifolds and 11 parallel straight channels. The length, width and depth of single channel with rectangular cross section was 48.0 mm, 2.5 mm and 2.0 mm, respectively. The experimental results indicated that the size of bubbles in microgravity condition is bigger than that in normal gravity. The longer the time, the bigger the bubbles. The velocity of bubbles rising is slower than that in normal gravity because buoyancy lift is very weak in microgravity. The flow pattern in anode channels could change from bubbly flow in normal gravity to slug flow in microgravity. The gas slugs blocked supply of reactants from channels to anode catalyst layer through gas diffusion layer. When the weakened mass transfer causes concentration polarization, the output performance of fuel cells declines.

Long-lived oscillatory incoherent electron dynamics in molecules: trans-polyacetylene oligomers

We identify an intriguing feature of the electron-vibrational dynamics of molecular systems via a computational examination of trans-polyacetylene oligomers. Here, via the vibronic interactions, the decay of an electron in the conduction band resonantly excites an electron in the valence band, and vice versa, leading to oscillatory exchange of electronic population between two distinct electronic states that lives for up to tens of picoseconds. The oscillatory structure is reminiscent of beating patterns between quantum states and is strongly suggestive of the presence of long-lived molecular electronic coherence. Significantly, however, a detailed analysis of the electronic coherence properties shows that the oscillatory structure arises from a purely incoherent process. These results were obtained by propagating the coupled dynamics of electronic and vibrational degrees of freedom in a mixed quantum-classical study of the Su-Schrieffer-Heeger Hamiltonian for polyacetylene. The incoherent process is shown to occur between degenerate electronic states with distinct electronic configurations that are indirectly coupled via a third auxiliary state by vibronic interactions. A discussion of how to construct electronic superposition states in molecules that are truly robust to decoherence is also presented

Short-range-order effects on intrinsic plasticity of metallic glasses

Through a systematical analysis of the elastic moduli for 137 metallic glasses (MGs) and 56 polycrystalline metals, we use a simple model developed by Knuyt et al. [J. Phys. F: Met. Phys. 16 (1986) p.1989; Phil. Mag. B 64 (1991) p.299] based on a Gaussian distribution for the first-neighbor distance to reveal the short-range-order (SRO) structural conditions for plasticity of MGs. It is found that the SRO structure with dense atomic packing, large packing dispersion and a significant anharmonicity of atomic interaction within an MG is favorable for its global plasticity. Although these conditions seem paradoxical, their perfect matching is believed to be a key for designing large plastic bulk MGs not only in compression but also in tension.

Plasma channeling by multiple short-pulse lasers

Channeling by a train of laser pulses into homogeneous and inhomogeneous plasmas is studied using particle-in-cell simulation. When the pulse duration and the interval between the successive pulses are appropriate, the laser pulse train can channel into the plasma deeper than a single long-pulse laser of similar peak intensity and total energy. The increased penetration distance can be attributed to the repeated actions of the ponderomotive force, the continuous between-pulse channel lengthening by the inertially evacuating ions, and the suppression of laser-driven plasma instabilities by the intermittent laser-energy cut-offs.