Impact of RNase L overexpression on viral and cellular growth and death

The biologic actions of interferons (IFNs) are complex and involve multiple biochemical mechanisms, including the 2-5A system, a regulated RNA decay pathway. The 2-5A system is implicated in the antipicornavirus activity of IFN and in the control of apoptosis. To further investigate involvement of the 2-5A system in the control of viral and cellular growth and death, human RNase L cDNA was stably expressed in murine 3T3 cells from a constitutive cytomegalovirus (CMV) promoter. A clonal cell line, 3T3/pLZ, was isolated that overexpressed RNase L by >100-fold compared with levels of the endogenous murine RNase L. Interestingly, human RNase L levels in 3T3/pLZ cells decreased 3-fold as cells entered a confluent, growth arrest state, suggesting autoregulation. Overexpression of human RNase L greatly enhanced both the cell growth inhibitory activity of IFN and the proapoptotic activity of staurosporine. Furthermore, high levels of RNase L suppressed the replication of diverse viruses: encephalomyocarditis virus, vesicular stomatitis virus, human parainfluenza virus-3, and vaccinia virus. Additional reductions in viral growth were obtained by treating 3T3/pLZ cells with IFN (a + beta) before infections. These results directly demonstrate the anticellular and antiviral potential of the 2-5A system.     

Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses

Small cell neuroendocrine carcinomas (SNECs) of the sinonasal tract are extremely uncommon tumors. We reviewed the clinicopathologic features of six cases of this neoplasm. There was no sex preponderance with three females and three males and a mean age at presentation of 51 years (range, 38 to 68). Two patients had disease limited to the nasal cavity, and in four the tumor involved the nasal cavity and maxillary or ethmoid sinuses. Involvement of the orbit was present in two patients. Surgery was the primary treatment. After a mean follow-up of 37 months, one patient died of local disease and liver metastases, four were alive with recurrent or metastatic disease, and one died of unrelated causes. The tumors were composed of sheets, nests, and trabeculae with extensive areas of necrosis and hemorrhage. The individual cells were small to intermediate in size and had scanty cytoplasm. The nuclei were oval or round and hyperchromatic with absent or inconspicuous nucleoli. Nuclear molding and crush artefact were present in five cases. All tumors had a high mitotic rate with frequent abnormal mitotic figures. All cases stained for Cam 5.2, neuron-specific enolase, and chromogranin. Five cases were positive for AE1:AE3, and four for synaptophysin. No case stained for S-100 protein, or neurofilaments. O-13 stained one case. No case contained EBV-RNA. SNECs of the nasal cavity and paranasal sinuses are aggressive tumors with pathological features similar to those of anaplastic small cell carcinomas of the lung. They exhibit morphological and immunophenotypic features different from olfactory neuroblastoma and should be distinguished from this tumor.     

Solid elements with rotational degrees of freedom: Part 1—hexahedron elements

This is the first of a two part paper on three-dimensional finite elements with rotational degrees of freedom (DOF). Part I introduces an 8-node solid hexahedron element having three translational and three rotational DOF per node. The corner rotations are introduced by transformation of the midside translational DOF of a 20-node hexahedron element. The new element produces a much smaller effective band width of the global system equations than does the 20-node hexahedron element having midside nodes. A small penalty stiffness is introduced to augment the usual element stiffness so that no spurious zero energy modes are present. The new element passes the patch test and demonstrates greatly improved performance over elements of identical shape but having only translational DOF at the corner nodes.     

A determinant of substrate specificity predicted from the acyl-acyl carrier protein desaturase of developing cat's claw seed

Cat's claw (Doxantha unguis-cati L.) vine accumulates nearly 80% palmitoleic acid (16:1Delta9) plus cis-vaccenic acid (18:1Delta11) in its seed oil. To characterize the biosynthetic origin of these unusual fatty acids, cDNAs for acyl-acyl carrier protein (acyl-ACP) desaturases were isolated from developing cat's claw seeds. The predominant acyl-ACP desaturase cDNA identified encoded a polypeptide that is closely related to the stearoyl (Delta9-18:0)-ACP desaturase from castor (Ricinis communis L.) and other species. Upon expression in Escherichia coli, the cat's claw polypeptide functioned as a Delta9 acyl-ACP desaturase but displayed a distinct substrate specificity for palmitate (16:0)-ACP rather than stearate (18:0)-ACP. Comparison of the predicted amino acid sequence of the cat's claw enzyme with that of the castor Delta9-18:0-ACP desaturase suggested that a single amino acid substitution (L118W) might account in large part for the differences in substrate specificity between the two desaturases. Consistent with this prediction, conversion of leucine-118 to tryptophan in the mature castor Delta9-18:0-ACP desaturase resulted in an 80-fold increase in the relative specificity of this enzyme for 16:0-ACP. The alteration in substrate specificity observed in the L118W mutant is in agreement with a crystallographic model of the proposed substrate-binding pocket of the castor Delta9-18:0-ACP desaturase.     

Detection and diagnosis of plant-wide oscillations from industrial data using the spectral envelope method

Plant-wide oscillations are common in many processes. Their effects propagate to many units and may impact the overall process performance. It is important to detect and diagnose the cause of such oscillations in order to rectify the situation. This paper proposes a new procedure to detect and diagnose plant-wide oscillations using routine operating data. A technique called spectral envelope is used to detect oscillations. The variables that have common oscillations are identified and categorized accurately by a statistical hypothesis test. A new index called the oscillation contribution index (OCI) is proposed to isolate the key variables as the potential root cause candidates of the common oscillation(s). Two industrial case studies are presented to demonstrate the utility and practicality of the proposed procedure.     

Frameworks for Enterprise Architecture

Enterprise architecture addresses the double challenge of increasing IT efficiency while continuing business innovation. Organizations can use enterprise architecture frameworks to manage system complexity and align business and IT resources. An enterprise architecture approach can help align business and IT resources and conform them to fundamental principles and common methodologies governing the entire information systems development process. In that sense, architectural frameworks are a convenient way to support such methodologies and separate roles that facilitate and implement these methodologies as needed. Still, many organizational and technical enterprise architecture challenges remain.     

Models and Metrics to Enable Energy-Efficiency Optimizations

Power consumption and energy efficiency are important factors in the initial design and day-to-day management of computer systems. Researchers and system designers need benchmarks that characterize energy efficiency to evaluate systems and identify promising new technologies. To predict the effects of new designs and configurations, they also need accurate methods of modeling power consumption.     

ALTAR in action: knowledge management

This paper describes the knowledge management (KM) aspects of an action research (AR) project that took place in a large U.K. manufacturing organisation, Britvic Soft Drinks Ltd. The ALTAR (Achieving Learning Through Action Research) approach described in an earlier paper was developed through the KM project described in this paper. The ALTAR approach was intended to facilitate organisational learning and academic research and the study involved a number of AR cycles at different levels of the collaborating organisation. Theoretical concepts were taken from the academic literature and were developed for practical use and fed back into the academic research. The knowledge value chain, in particular, helped the organisation to focus on the essential aspects of KM. The research-led thinking was useful in helping Britvic staff to define and understand the importance of knowledge, to identify what knowledge assets they owned and to understand how that knowledge could be harnessed. The research facilitated individuals' understanding of how better to access the knowledge of others and to share their own knowledge to benefit the whole organisation. From an academic point of view, the AR project facilitated academic research, stimulated organisational change and learning provided useful material for research outputs, teaching and learning and promoted future research opportunities.     

High doped MBE Si p–n and n–n heterojunction diodes on 4H-SiC

The physical and electrical properties of heavily doped silicon (5×10¹⁹ cm⁻³) deposited by molecular beam epitaxy (MBE) on 4H-SiC are investigated in this paper. Silicon layers on silicon carbide have a broad number of potential applications including device fabrication or passivation when oxidised. In particular, Si/SiC contacts present several atractive material advantages for the semiconductor industry and especially for SiC processing procedures for avoiding stages such as high temperature contact annealing or SiC etching. Si films of 100 nm thickness have been grown using a MBE system after different cleaning procedures on n-type (0 0 0 1) Si face 8° off 4H-SiC substrates. Isotype (n–n) and an-isotype (p–n) devices were fabricated at both 500 and 900 °C using antimonium (Sb) or boron (B), respectively. X-ray diffraction analysis (XRD) and scanning electronic mircorscope (SEM) have been used to investigate the crystal composition and morphology of the deposited layers. The electrical mesurements were performed to determine the rectifiying contact characteristics and band offsets.     

A real-coding jumping gene genetic algorithm (RJGGA) for multiobjective optimization

This paper presents a real jumping gene genetic algorithm (RJGGA) as an enhancement of the jumping gene genetic algorithm (JGGA) [T.M. Chan, K.F. Man, K.S. Tang, S. Kwong, A jumping gene algorithm for multiobjective resource management in wideband CDMA systems, The Computer Journal 48 (6) (2005) 749-768; T.M. Chan, K.F. Man, K.S. Tang, S. Kwong, Multiobjective optimization of radio-to-fiber repeater placement using a jumping gene algorithm, in: Proceedings of the IEEE International Conference on Industrial Technology (ICIT 2005), Hong Kong, 2005, pp. 291-296; K.F. Man, T.M. Chan, K.S. Tang, S. Kwong, Jumping-genes in evolutionary computing, in: Proceedings of the IEEE IECON’2004, Busan, 2004, pp. 1268-1272]. JGGA is a relatively new multiobjective evolutionary algorithm (MOEA) that imitates a jumping gene phenomenon discovered by Nobel Laureate McClintock during her work on the corn plants. The main feature of JGGA is that it only has a simple operation in which a transposition of gene(s) is induced within the same or another chromosome in the genetic algorithm (GA) framework. In its initial formulation, the search space solutions are binary-coded and it inherits the customary problems of conventional binary-coded GA (BCGA). This issue motivated us to remodel the JGGA into RJGGA. The performance of RJGGA has been compared to other MOEAs using some carefully chosen benchmark test functions. It has been observed that RJGGA is able to generate non-dominated solutions with a wider spread along the Pareto-optimal front and better address the issues regarding convergence and diversity in multiobjective optimization.