Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes

Recent reports have demonstrated fusion of the TEL gene on 12p13 to the JAK2 gene on 9p24 in human leukemias. Three variants have been identified that fuse the TEL pointed (PNT) domain to (i) the JAK2 JH1-kinase domain, (ii) part of and (iii) all of the JH2 pseudokinase domain. We report that all of the human TEL/JAK2 variants, and a human/mouse chimeric hTEL/mJAK2(JH1) fusion gene, transform the interleukin-3 (IL-3)-dependent murine hematopoietic cell line Ba/F3 to IL-3-independent growth. Transformation requires both the TEL PNT domain and JAK2 kinase activity. Furthermore, all TEL/JAK2 variants strongly activated STAT 5 by phosphotyrosine Western blots and by electrophoretic mobility shift assays (EMSA). Mice (n = 40) transplanted with bone marrow infected with the MSCV retrovirus containing either the hTEL/mJAK2(JH1) fusion or its human counterpart developed a fatal mixed myeloproliferative and T-cell lymphoproliferative disorder with a latency of 2-10 weeks. In contrast, mice transplanted with a TEL/JAK2 mutant lacking the TEL PNT domain (n = 10) or a kinase-inactive TEL/JAK2(JH1) mutant (n = 10) did not develop the disease. We conclude that all human TEL/JAK2 fusion variants are oncoproteins in vitro that strongly activate STAT 5, and cause lethal myelo- and lymphoproliferative syndromes in murine bone marrow transplant models of leukemia.     

Pulmonary vein stenosis after catheter ablation of atrial fibrillation

BACKGROUND: This report describes the complication of pulmonary vein stenosis with resultant severe pulmonary hypertension that developed in 2 patients after successful catheter ablation of chronic atrial fibrillation. METHODS AND RESULTS: Three months after successful catheter ablation of atrial fibrillation, both patients developed progressive dyspnea and pulmonary hypertension. Both were found to have severe stenosis of all 4 pulmonary veins near the junction with the left atrium. Balloon dilation of the stenotic pulmonary veins was performed in these patients, with improvement in dyspnea and pulmonary hypertension. CONCLUSIONS: The complication of pulmonary vein stenosis is potentially life-threatening, and the application of radiofrequency current within the pulmonary veins with standard catheter technology should be avoided. This complication can be treated with balloon dilation, although the long-term course is unknown.     

Dimensions of control: Correlations between MMPI and I-E scores.

Administered Rotter's Internal versus External Locus of Control (I-E) scale and the MMPI to 25 volunteer members of a suburban rescue squad. I-E scores correlated with 3 MMPI scales: negatively with the K and Hy scales and positively with the F scale. A comparison of these relationships with those found in a sample of alcoholics is made. It is suggested that the correlations observed indicate "that a sense of control over external events is related to self-control and competence in handling internal events." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of the impedance model of an implanted cochlear prosthesis from intracochlear potential measurements

Those suffering from a severe to profound sensorineural hearing loss can obtain substantial benefit from a cochlear implant prosthesis. An electrode array implanted in the inner ear stimulates auditory nerve fibers by direct injection of electrical current. A major limitation of today's technology is the imprecise control of intracochlear current flow, particularly the relatively wide spread of neural excitation. A better understanding of the intracochlear electrical fields is, therefore, required. This paper analyzes the structure of intracochlear potential measurements in relation to both the subject's anatomy and to the properties of the electrode array. An electrically equivalent network is proposed, composed of small lumped circuits for the interface impedance and for the cochlear tissues. The numerical methods required to estimate the model parameters from high-quality electrical potential recordings are developed. Finally, some models are presented for subjects wearing a Clarion CII device with a HiFocus electrode and discussed in terms of model reliability.     

CAutoCSD – Evolutionary Search and Optimisation Enabled Computer Automated Control System Design

This paper attempts to set a unified scene for various linear time-invariant (LTI) control system design schemes, by transforming the existing concept of "computer-aided control system design" (CACSD) to novel "computer-automated control system design" (CAutoCSD). The first step towards this goal is to accommodate, under practical constraints, various design objectives that are desirable in both time and frequency domains. Such performance-prioritised unification is aimed at relieving practising engineers from having to select a particular control scheme and from sacrificing certain performance goals resulting from pre-commitment to such schemes. With recent progress in evolutionary computing based extra-numeric, multi-criterion search and optimisation techniques, such unification of LTI control schemes becomes feasible, analytical and practical, and the resultant designs can be creative. The techniques developed are applied to, and illustrated by, three design problems. The unified approach automatically provides an integrator for zero-steady state error in velocity control of a DC motor, and meets multiple objectives in the design of an LTI controller for a non-minimum phase plant and offers a high-performance LTI controller network for a non-linear chemical process.     

Thermal properties of cowpea flour: a study by differential scanning calorimetry

The thermal properties of 12 varieties of cowpea flour were studied by differential scanning calorimetry (DSC). Flour samples were prepared to a paste of 60% moisture content and sealed in standard DSC pans. Samples were scanned at a heating rate of 5 degrees C/min over a scan range of 40- 130 degrees C. Samples exhibited single major endotherms, which occurred over varied temperatures. The transition enthalpy (deltaH) ranged between 1.4 J/g and 4.7 J/g. Transition onset (T(o)) and transition peak (T(p)) temperatures ranged between 75-78 degrees C and 78-82 degrees C,respectively. All the DSC parameters measured varied significantly among the varieties. The transition enthalpy (deltaH) was the most discriminating parameter and accounted for 80% of the total variance. The major chemical components of cowpea flour, starch amylose and protein are significant predictors of deltaH. Protein denaturation appears to be a significant modification which occurs during processing of cowpea seeds to flour. The transition enthalpy deltaH could become an important functional index of cowpea flour when related to some quality parameters in products that contain the flour.     

Imaging of the expansion of femtosecond-laser-produced silicon plasma atoms by off-resonant planar laser-induced fluorescence

Planar laser-induced fluorescence measurements were used to investigate the expansion dynamics of a femtosecond laser-induced plasma. Temporally and spatially resolved measurements were performed to monitor the atoms that were ablated from a silicon target. A dye laser (lambda = 288.16 nm) was used to excite fluorescence signals. The radiation of an off-resonant transition (Si 390.55 nm) was observed at different distances from the target surface. This allowed easy detection of the ablated Si atoms without problems caused by scattered laser light. Abel inversion was applied to obtain the radial distribution of the Si atoms. The atom distribution in the plasma shows some peculiarities, depending on the crater depth.     

Application of femtosecond laser ablation time-of-flight mass spectrometry to in-depth multilayer analysis

A femtosecond laser system was used in combination with a time-of-flight mass spectrometer (TOF-MS) for in-depth profiling of semiconductor and metal samples. The semiconductor sample was a Co-implanted (10(17) ions/cm3) silicon wafer that had been carefully characterized by other established techniques. The total depth of the shallow implanted layer was 150 nm. As a second sample, a thin film metal standard had been used (NIST 2135c). This standard consisted of a silicon wafer with nine alternating Cr and Ni layers, each having a thickness of 56 and 57 nm, respectively. An orthogonal TOF-MS setup was implemented. This configuration was optimized until a sufficient mass resolution of 300 (m/delta m) and sensitivity was achieved. The experiments revealed that femtosecond-laser ablation TOF-MS is capable of resolving the depth profiles of these demanding samples. The poor precision of the measurements is discussed, and it is shown that this is due to pulse-to-pulse stability of the current laser system. Femtosecond-laser ablation TOF-MS is shown to be a promising technique for rapid in-depth profiling with a good lateral resolution of various multilayer thin film samples.     

Effects of abomasal infusion of conjugated linoleic acid on milk fat concentration and yield from pasture-fed dairy cows

The aim of this study was to investigate the effects of conjugated linoleic acid supplementation on the synthesis of milk fat in pasture-fed Friesian cows. In four cows, a commercial mixture containing 62.3% (wt/vol) conjugated linoleic acid was infused intraabomasally to avoid rumen fermentation and biohydrogenation. The design was a 4 x 4 Latin square in which each cow received infusions of 0, 20, 40, and 80 g/d of conjugated linoleic acid mixture for 4 d. Cows were fed freshly cut ryegrass/white clover pasture ad libitum. Milk fat concentration was decreased by 36, 43, and 62% and milk fat yield was decreased by 32, 36, and 60% by the 20, 40, and 80 g of conjugated linoleic acid/d treatments. Dry matter intake, milk protein concentration, and protein yield were unaffected by treatments; however, milk yield was increased by 11% during the 40-g conjugated linoleic acid/d treatment. The effects of conjugated linoleic acid infusion were most pronounced in reducing de novo fatty acid synthesis and desaturation. Results show that the inhibitory effect of this conjugated linoleic acid mixture on milk fat synthesis occurs in pasture-fed cows, and demonstrate the potential to dramatically alter gross milk composition. This technology could offer a management tool to manipulate milk composition and energy demands of pasture-fed cows.