Variety Of Insertions Research Articles

Analysis and Optimization of Machinability of Al<sub>2</sub>O<sub>3</sub> and Fly Ash Reinforced Aluminum Hybrid Composites Using Carbide Inserts

Aluminum matrix hybrid composites reveal excellent mechanical behavior compared to traditional materials for a wide range of conditions and applications. However, the machining of this kind of composite is a challenging job due to its improved mechanical hardness. The problems faced during the cutting of these composites are increased machining forces, poor surface quality, and increased tool wear. Many types of research are still in progress across the world to overcome these issues by using a variety of inserts and processing constraints. So, this paper is mainly focused on the study of the machinability of aluminum hybrid composites. The composites are synthesized by employing stir casting via varying the filler content, stirring duration, and speed. The fabricated composites are machined using coated and uncoated carbide inserts. Machining forces, surface roughness, and insert wear are assessed to learn the machinability of these materials by varying the machining constraints. Taguchi analysis was employed to assess the effect of the constraints on the retorts. Keywords. Aluminum Hybrid Composites, Stir Casting, Machinability, Taguchi Analysis.

Experimental investigation on influence of engagement angle and tool geometry on plunge milling

Taking advantage of the superior cutter axial stiffness, plunge milling provides a higher material removal rate in rough milling for components with deep cavities. Tool wear depending on cutting parameters of radial cutting width, axial cutting depth, step interval, feedrate, and spindle speed has been studied by several researchers. For a more comprehensive understanding of the wear mechanism, this study investigates the influences of tool engagement angle and tool geometry on tool wear based on multiple sets of machining tests. The development of tool wear during plunge milling is monitored. Results show that tool wear of insert with large engagement angle mainly exists on minor edge, which is caused by increased tool deflection. When the radial distance equals to tool radius, optimal engagement angle can be achieved while considering both tool life and machining efficiency. The experimental results show that tool life of insert with rake angle of 22° is 6.5% higher than rake angle of 15°. Smaller corner radius has positive influences on tool life improvement. Surprisingly, tool life of insert without cutting edge chamfer is 3.6 times than insert with cutting edge chamfer. The best tool geometric parameters of plunge insert can then be identified among a variety of inserts. This work is useful for cutting tool producers and manufacturers to optimize tool geometry and machining parameters.

806. Immunologic Improvement after Gene Therapy in 3 Preadolescents with X-Linked Severe Combined Immunodeficiency (XSCID)

XSCID results from mutations in the IL2RG gene encoding the common gamma chain (|[gamma]|c) shared by several cytokine receptors. Gene therapy as primary treatment for XSCID infants can restore immunity, but 2 teenagers with XSCID did not benefit from gene transfer to autologous bone marrow CD34+ cells. We used retrovirally transduced autologous peripheral mobilized CD34+ cells to treat 3 XSCID preadolescents 10-14 years old with immunodeficiency despite haploidentical bone marrow transplants (BMT). After 6-24 m we found selective gene marking of T cells in all 3 patients, with variable evidence of immunologic improvement. Prior to gene therapy, they had growth failure, frequent infections, diarrhea, T lymphocytopenia, and poor T, NK and B cell function. Each received 30-40 million cells/kg transduced ex vivo with GALV-MFGS-|[gamma]|c. Patient 1 (P1) had a poly-A addition signal mutation allowing residual |[gamma]|c function and had rejected 4 BMTs. At 24 m post gene therapy P1 had provirus detected by quantitative PCR in 4.3% of T cells and 0.1% of both B and myeloid cells. In P2 proviral marking at 18 m was 110% (or average copy number of 1.1), 5% and 0.1% in T, B and myeloid cells, respectively. P3 at 6 m had 22% marking in T cells, with low levels in other leukocyte lineages. CD4+ T cell counts in all patients have increased, but remain below the normal range. P1 has experienced improvement in well-being and resolution of lifelong diarrhea, abdominal distention and rashes; he has not had infections except for an otitis externa 12 m after treatment. A 0.5 cm submandibular nodule consistent with a lymph node arose 6 m post gene therapy and has not changed. After gene therapy P2 has had less frequent diarrhea and respiratory infections. At 6 m post treatment his T cells developed normal proliferative responses to mitogens and Candida antigen. At 12 m, P2 acquired detectable CD4+CD45RA+ T cells and T cell receptor excision circles, indicating new thymic output; donor chimerism assay showed autologous T cell expansion from 49% before gene therapy to 87% at 12 m and beyond. P3 has also reported improved well-being, exercise tolerance and appetite at 6 m; he has had increases in T cell number and proliferative responses to mitogens. Analysis of retroviral insertion sites in P1 and P3 consistently showed polyclonality. T cells of P2 had an oligoclonal pattern by LAM-PCR, but linker-mediated PCR yielded a wide variety of insertions. Furthermore, both V|[beta]| TCR usage and spectratyping showed increasing diversity after gene therapy. Proviral insertions near LMO2, implicated in European XSCID leukemia cases, have not been identified. Our preliminary results suggest that gene therapy may benefit some XSCID patients who have failed previous BMT treatment. Prior production of allogeneic T cells in P2 may have helped to preserve his thymic function. Further follow-up will establish long-term safety, efficacy and indications for XSCID gene therapy in preadolescent subjects with XSCID.

Targeted modification of the complete chicken lysozyme gene by poxvirus-mediated recombination

We have developed a novel ex vivo system for the rapid one-step targeted modification of large eucaryotic DNA sequences. The highly recombinant environment resulting from infection of rabbit cornea cells with the Shope fibroma virus was exploited to mediate precise modifications of the complete chicken lysozyme gene domain (21.5 kb). Homologous recombination was designed to occur between target DNA (containing the complete lysozyme gene domain) maintained in a lambda bacteriophage vector and modified targeting DNA maintained in a plasmid. The targeting plasmids were designed to transfer exogenous sequences (for example, beta-galactosidase alpha-complement, green fluorescent protein, and hydrophobic tail coding sequences) to specific sites within the lysozyme gene domain. Cotransfection of the target phage and a targeting plasmid into Shope fibroma virus infected cells resulted in the poxvirus-mediated transfer of the modified sequences from plasmid to phage. Phage DNA (recombinant and nonrecombinant) was then harvested from the total cellular DNA by packaging into lambda phage particles and correct recombinants were identified. Four different gene-targeting pairings were carried out, and from 3% to 11% of the recovered phages were recombinant. Using this poxvirus-mediated targeting system, four different regions of the chicken lysozyme gene domain have been modified precisely by our research group overall with a variety of inserts (6-971 bp), deletions (584-3000 bp), and replacements. We have never failed to obtain the desired recombinant. Poxvirus-mediated recombination thus constitutes a routine, rapid, and remarkably efficient genetic engineering system for the precise modification of large eucaryotic gene domains when compared with traditional practices.