Next-generation sequencing with a myeloid gene panel in core-binding factor AML showed KIT activation loop and TET2 mutations predictive of outcome.

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.

Academic background of oral and maxillofacial specialty trainees in the United Kingdom.

INTRODUCTION: The academic profile of a specialty can be measured in a number of ways. In the selection process for entry into higher training in oral & maxillofacial surgery (OMFS) and for interface fellowships in surgery trainees are awarded points for papers published, presentations, teaching and learning, grants and higher degrees. General information about career development can provide trainers, and trainees, with information and guidance. METHODS: A web-based questionnaire was developed and distributed via electronic mailing lists to all OMFS specialist trainees. Basic demographic information was collected. Previous, current and future career plans were questioned, as was academic background in terms of publications, presentations, prizes and research grants as well as further degrees and examinations. RESULTS: One hundred and five OMFS specialty registrar trainees (StR) replied (76.6% response rate). 83.3% were male and the average age of all trainees was 37 years old. 74.7% obtained a training post on the first application. 62.6% of trainees were keen to practice in trauma surgery. 76.6% were keen to undertake a fellowship. 20.9% were keen to be involved in academia (teaching) and 9.9% in academia (research). 22.1% of trainees had obtained grants. CONCLUSION: Those involved in appointing to training programmes will now be able to see the level of competition. Future applicants to training programmes in oral and maxillofacial surgery in the United Kingdom are now aware of the level of competition. OMFS is not immune to the 'academic crisis' that exists in other surgical specialties, and the completion of higher degrees and entry in to academic careers should be encouraged and supported among trainees with an interest.

Localization of burn mark under an abnormal topography on MOSFET chip surface using liquid crystal and emission microscopy tools.

This article focuses on the localization of burn mark in MOSFET and the scanning electron microscope (SEM) inspection on the defect location. When a suspect abnormal topography is shown on the die surface, further methods to pin-point the defect location is necessary. Fault localization analysis becomes important because an abnormal spot on the chip surface may and may not have a defect underneath it. The chip surface topography can change due to the catastrophic damage occurred at layers under the chip surface, but it could also be due to inconsistency during metal deposition in the wafer fabrication process. Two localization techniques, liquid crystal thermography and emission microscopy, were performed to confirm that the abnormal topography spot is the actual defect location. The tiny burn mark was surfaced by performing a surface decoration at the defect location using hot hydrochloric acid. SEM imaging, which has the high magnification and three-dimensional capabilities, was used to capture the images of the burn mark.

Fault diagnosis of the polypropylene production process (UNIPOL PP) using ANFIS.

The performance of a chemical process plant can gradually degrade due to deterioration of the process equipment and unpermitted deviation of the characteristic variables of the system. Hence, advanced supervision is required for early detection, isolation and correction of abnormal conditions. This work presents the use of an adaptive neuro-fuzzy inference system (ANFIS) for online fault diagnosis of a gas-phase polypropylene production process with emphasis on fast and accurate diagnosis, multiple fault identification and adaptability. The most influential inputs are selected from the raw measured data sets and fed to multiple ANFIS classifiers to identify faults occurring in the process, eliminating the requirement of a detailed process model. Simulation results illustrated that the proposed method effectively diagnosed different fault types and severities, and that it has a better performance compared to a conventional multivariate statistical approach based on principal component analysis (PCA). The proposed method is shown to be simple to apply, robust to measurement noise and able to rapidly discriminate between multiple faults occurring simultaneously. This method is applicable for plant-wide monitoring and can serve as an early warning system to identify process upsets that could threaten the process operation ahead of time.

Two-dimensional model of low Mach number vortex sound generation in a lined duct.

The sound generated by a vortex moving across a duct section lined with porous materials and the corresponding vortex dynamics are studied numerically in the present investigation. The combined effects of the effective fluid density, the flow resistance, the length, and the thickness of the porous linings on the vortex dynamics and sound generation are examined in detail. Results show that stronger sound radiation will take place when the length and the thickness of the porous linings are increased or when the effective fluid density is reduced. The flow resistance can only result in stronger sound radiation within a range whose width depends on the above-mentioned system parameters. Such sound amplification cannot be achieved when the initial vortex height gets closer and closer to the duct centerline. The present results also indicate the strong correlation between vortex acceleration and the sound radiation under the actions of the porous linings.

A cell penetrating heme oxygenase protein protects heart graft against ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is an unavoidable barrier that significantly affects outcome of solid organ transplantation. Here, we establish a protein transduction system to extend graft preservation time and to prevent I/R injury in heart transplantation. We generated a recombinant heme oxygenase-1 (HO-1) protein containing a modified protein transduction domain (PTD). PTD could cross cover cell membrane and carry target molecule to parenchymal cells of cold-preserved heart grafts. The newly generated PTD-HO-1 protein localized mainly in subcellular membrane organelle and nucleus after delivery that significantly prolonged cold preservation of heart grafts. This effect was associated with significantly less endothelial cell activation, less neutrophil and macrophage infiltration in PTD-HO-1-transduced heart grafts after reperfusion as compared with controls. In addition, transduction of PTD-HO-1 protein to heart graft significantly suppressed the I/R injury-associated myocardiocyte apoptosis. The infarct areas of heart graft after I/R injury were significantly reduced after PTD-HO-1 protein treatment. We show here for the first time that PTD can maintain its biological activities during cold preservation. Transduction of cell penetrating HO-1 protein significantly prolongs the cold preservation time and protects the graft from the I/R injury. This approach represents a novel method for the improvement of the overall outcome of organ transplantation.

Emergency department thoracotomy for pericardiac tamponade.

A 31-year-old man with a penetrating chest injury presented acutely with pulseless electrical activity, as a result of a ventricular laceration causing pericardial tamponade. Emergency department thoracotomy was performed to release the tamponade and he was operated on immediately to repair the laceration. He subsequently survived and was discharged to a community hospital for rehabilitation. We present this case of penetrating cardiac injury in which the patient arrived in extremis and for which emergency department thoracotomy was performed, and we discuss the role of emergency thoracotomy, its indications and outcome indicators.

Vortex sound under the influence of a piecewise porous material on an infinite rigid plane.

The vortex dynamics and the sound generation by an inviscid vortex in the presence of a finite length porous material on an otherwise rigid plane are studied numerically in the present study in an attempt to understand the sound generation near the surface of a wall lining in a lined duct. The combined effects of the effective fluid density and flow resistance inside the porous material, and the length and thickness of the porous material on the sound generation process are examined in detail. Results obtained demonstrate the sound pressure is longitudinal dipole and show how seriously the above-mentioned parameters are affecting the vortex sound pressure under the influence of the porous material.

Sound generated by vortices in the presence of a porous half-cylinder mounted on a rigid plane.

The sound generated by a single vortex and by two identical vortices in the presence of a half-cylinder made of porous material mounted on a rigid horizontal plane is studied theoretically using the acoustic analogy and the matched asymptotic expansion method. Both longitudinal and transverse dipoles are observed upon the introduction of the porous cylinder, but the former is considerably stronger than the latter in all the cases studied. Results suggest that the amplitudes of the dipoles and the overall acoustical energy radiated can be higher than that in the rigid cylinder case under some suitable combinations of flow parameters, especially when the flow resistance inside the porous material seen by the vortices is very small.

The SMN complex: an assembly machine for RNPs.

In eukaryotic cells, the biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and likely other RNPs is mediated by an assemblyosome, the survival of motor neurons (SMN) complex. The SMN complex, composed of SMN and the Gemins (2-7), binds to the Sm proteins and to snRNAs and constructs the heptameric rings, the common cores of Sm proteins, on the Sm site (AU(56)G) of the snRNAs. We have determined the specific sequence and structural features of snRNAs for binding to the SMN complex and Sm core assembly. The minimal SMN complex-binding domain in snRNAs (except U1) is composed of an Sm site and a closely adjacent 3'stem-loop. Remarkably, the specific sequence of the stemloop is not important for SMN complex binding, but it must be located within a short distance of the 3'end of the RNA for an Sm core to assemble. This minimal snRNA-defining "snRNP code" is recognized by the SMN complex, which binds to it directly and with high affinity and assembles the Sm core. The recognition of the snRNAs is provided by Gemin5, a component of the SMN complex that directly binds the snRNP code. Gemin5 is a novel RNA-binding protein that is critical for snRNP biogenesis. Thus, the SMN complex is the identifier, as well as assembler, of the abundant class of snRNAs in cells. The function of the SMN complex, previously unanticipated because RNP biogenesis was believed to occur by self-assembly, confers stringent specificity on otherwise potentially illicit RNA-protein interactions.

Sound transmission across duct constrictions with and without tapered sections.

The sound power transmission loss across duct constrictions with linearly tapered sections is studied with the finite element method. Results show that the acoustic energy distributions of transmitted waves at high frequency depend critically on the exit configuration of the constriction. The corresponding strengths of these waves are very much affected by the entrance setup of the constriction. The difference between inlet and outlet impedance of a constriction leads to weaker resonant sound transmission.

Sound transmission across a smooth nonuniform section in an infinitely long duct.

Sound transmission across a nonuniform section in an infinite duct is studied numerically using the finite element method. An impedance matched absorptive portion is added to each end of the computational domain so as to avoid the undesirable higher mode reflection that will otherwise take place there. Results suggest that the sound fields downstream of the nonuniform section inlet are complicated and cannot be easily described by the conventional solution of the wave equation. The distribution of acoustic energy among the various propagating modes well downstream from the outlet of the nonuniform section is also discussed. Results show that the first symmetrical higher mode is important for all cases. The plane wave becomes important at high frequency with high rate of change of the cross-sectional area when the section is a convergent one.

Ribosomal DNA replication fork barrier and HOT1 recombination hot spot: shared sequences but independent activities.

In the ribosomal DNA of Saccharomyces cerevisiae, sequences in the nontranscribed spacer 3' of the 35S ribosomal RNA gene are important to the polar arrest of replication forks at a site called the replication fork barrier (RFB) and also to the cis-acting, mitotic hyperrecombination site called HOT1. We have found that the RFB and HOT1 activity share some but not all of their essential sequences. Many of the mutations that reduce HOT1 recombination also decrease or eliminate fork arrest at one of two closely spaced RFB sites, RFB1 and RFB2. A simple model for the juxtaposition of RFB and HOT1 sequences is that the breakage of strands in replication forks arrested at RFB stimulates recombination. Contrary to this model, we show here that HOT1-stimulated recombination does not require the arrest of forks at the RFB. Therefore, while HOT1 activity is independent of replication fork arrest, HOT1 and RFB require some common sequences, suggesting the existence of a common trans-acting factor(s).

Autologous bone marrow transplantation for patients with acute myeloid leukaemia: prospective follow-up study.

OBJECTIVE: To study the use of autologous bone marrow transplantation to treat acute myeloid leukaemia when complete remission had been achieved and when no human leukocyte antigen matched related donor was available. DESIGN: Prospective follow-up study. SETTING: Government hospital, Hong Kong. PATIENTS: Eight patients (median age, 34 years [range, 16-45 years]) with acute myeloid leukaemia in whom complete remission had been achieved. INTERVENTION: Conditioning regimen of carmustine, amsacrine, etoposide VP-16, cytarabine, and infusion of unpurged marrow. MAIN OUTCOME MEASURES: Median time taken to reach neutrophil and platelet counts of > or =0.5 x 10(9) /L and > or = x 10(9) /L, respectively; mortality and relapse rates; and follow-up regimens used. RESULTS: Engraftment was successfully achieved in all patients and there were no early procedure-related mortalities. The median times required to reach a neutrophil count of > or =0.5 x 10(9) /L and a platelet count of > or =20 x 10(9) /L were 30 days (range, 18-36 days) and 38 days (range, 15-53 days), respectively. The median duration of hospital stay was 37 days (range, 25-43 days). Two patients died of a relapse of leukaemia at 6 and 9 months post-transplantation. Two patients experienced relapses: one at 8 months post-transplantation, for which conventional chemotherapy was restarted, and one at 18 months; treatment with all-trans-retinoic acid and conventional chemotherapy achieved a third complete remission in the latter patient, who had acute promyelocytic leukaemia. Continuous remission has been achieved in four of the eight patients after a median follow-up duration of 26 months (range, 6-43 months). CONCLUSION: Autologous bone marrow transplantation is an acceptable treatment for patients with acute myeloid leukaemia who lack a human leukocyte antigen-matched related donor.

A new structural variation on the methanesulfonylphenyl class of selective cyclooxygenase-2 inhibitors.

By inserting an oxygen link between the 3-fluorophenyl and the lactone ring of 5,5-dimethyl-3-(3fluorophenyl)-4-(4-methanesulfonylphenyl)-2 (5H)-furanone 1 (DFU), analogs with enhanced in vitro COX-2 inhibitory potency as well as in vivo potency in models of inflammation were obtained.

Synthesis and biological evaluation of 3-heteroaryloxy-4-phenyl-2(5H)-furanones as selective COX-2 inhibitors.

A series of 3-heteroaryloxy4-phenyl-2-5H)-furanones were prepared and evaluated for their potency and selectivity as COX-2 inhibitors. This led to the identification of L-778,736 as a potent, orally active and selective inhibitor of the COX-2 enzyme.

Regional differences in the developing cerebral cortex revealed by ephrin-A5 expression.

The development of axonal connections between thalamic nuclei and their cortical target areas occurs in a highly specific manner. To explore the mechanisms of thalamocortical axon pathfinding, we investigated the expression of several members of the ephrin and Eph gene families in the forebrain. The Eph ligand ephrin-A5 was expressed in three distinct gradients during the development of the telencephalon. The first gradient occurred in the cortical ventricular zone and established ephrin-A5 as one of the earliest markers distinguishing cells residing in the anterior versus posterior cortical neuroepithelium. The second gradient was apparent in the subplate and occurred in spatial opposition to a distinct gradient for the low-affinity NGF receptor p75. This finding reveals that different regions of the early subplate are molecularly heterogeneous. Third, we confirmed that ephrin-A5 is expressed in a bi-directional gradient in the cortical plate, with highest levels in the somatomotor cortex. Three putative receptors for ephrin-A5 -- EphA3, EphA4 and EphA5 -- showed distinct expression patterns in the developing thalamus. The graded distributions of ephrin-A5 in the developing subplate and cortex and the expression of its receptors in the thalamus are consistent with the notion that the Eph ligands and their receptors may function in the topographic mapping of thalamic axons to specific cortical areas.