An Integrated Evolutionary Algorithm for Expensive Global Optimization

We propose an integrated algorithm named low dimensional simplex evolution extension (LDSEE) for expensive global optimization in which only a very limited number of function evaluations is allowed. The new algorithm accelerates an existing global optimization, low dimensional simplex evolution (LDSE), by using radial basis function (RBF) interpolation and tabu search. Different from other expensive global optimization methods, LDSEE integrates the RBF interpolation and tabu search with the LDSE algorithm rather than just calling existing global optimization algorithms as subroutines. As a result, it can keep a good balance between the model approximation and the global search. Meanwhile it is self-contained. It does not rely on other GO algorithms and is very easy to use. Numerical results show that it is a competitive alternative for expensive global optimization.

Construction, extension and evaluation of the improved smoking kiln (Banda) in Kainji Lake area

Fish smoking, as a traditional occupation of fishermen and women in Kainji Lake Area (Nigeria) is done using simple traditional ovens called 'Banda', the fuel for the smoking being almost hundred percent dependent on wood. A simple modification was made to the traditional 'Banda' oven using a damper to prevent burning of the fish. A comparison of the improved and the traditional 'Banda' was made. The results indicate that fuel wood consumption was reduced 52 percent by using the improved 'Banda', which implied that 50 percent of fish processor's income could be saved through the adoption of this technology. The most important advantage of the improved kiln, fuel wood conservation, represents for fishers a problem of an economic importance. Whilst they are aware that it is becoming much more difficult to get the needed fuel wood, the children can still conveniently collect enough wood for both home use and processing activities. The cost of the components of the improved kiln, when compared with the traditional version may be considered quite significant, and hence the reluctance of the fish processors in constructing similar ones. Selected blacksmiths were trained to continue the fabrication of the kiln component. The training was carried out to assure that the improved kiln will be constructed even after the project will end to support the fabrication

The role of extension in fisheries development among rural communities

It is a common knowledge that there exists a wide gap between domestic fish production and demand in Nigeria. Government recognizes this situation and has in recent years encouraged fish production through fishing inputs subsidies, DFRRI assisted fingerlings production among others. Despite these efforts, impact at the grassroots has been low. One of the major reasons for the failure could be attributable to inadequate involvement of rural communities in fish production. This missing link appears to be ignorance of local communities in harnessing this potential to stimulate fish production. There is therefore the need to educate the rural dwellers through effective extension services. Strategies to achieve the required awareness have been discussed

Structure-function studies of serine hydrolases: synthesis of a gene for ∝-lytic protease and the purification and characterization of a mutant β-lactamase

The author has constructed a synthetic gene for ∝-lytic protease. Since the DNA sequence of the protein is not known, the gene was designed by using the reverse translation of ∝-lytic protease's amino acid sequence. Unique restriction sites are carefully sought in the degenerate DNA sequence to aid in future mutagenesis studies. The unique restriction sites are designed approximately 50 base pairs apart and their appropriate codons used in the DNA sequence. The codons used to construct the DNA sequence of ∝-lytic protease are preferred codons in E-coli or used in the production of β-lactamase. Codon usage is also distributed evenly to ensure that one particular codon is not heavily used. The gene is essentially constructed from the outside in. The gene is built in a stepwise fashion using plasmids as the vehicles for the ∝-lytic oligomers. The use of plasmids allows the replication and isolation of large quantities of the intermediates during gene synthesis. The ∝-lytic DNA is a double-stranded oligomer that has sufficient overhang and sticky ends to anneal correctly in the vector. After six steps of incorporating ∝-lytic DNA, the gene is completed and sequenced to ensure that the correct DNA sequence is present and that no mutations occurred in the structural gene.

β-lactamase is the other serine hydrolase studied in this thesis. The author used the class A RTEM-1 β- lactamase encoded on the plasmid pBR322 to investigate the roll of the conserved threonine residue at position 71. Cassette mutagenesis was previously used to generate all possible amino acid substitutions at position 71. The work presented here describes the purification and kinetic characterization of a T71H mutant previously constructed by S. Schultz. The mutated gene was transferred into plasmid pJN for expression and induced with IPTG. The enzyme is purified by column chromatography and FPLC to homogeneity. Kinetic studies reveal that the mutant has lower k_(cat) values on benzylpenicillin, cephalothin and 6-aminopenicillanic acid but no changes in k_m except for cephalothin which is approximately 4 times higher. The mutant did not change siginificantly in its pH profile compared to the wild-type enzyme. Also, the mutant is more sensitive to thermal denaturation as compared to the wild-type enzyme. However, experimental evidence indicates that the probable generation of a positive charge at position 71 thermally stabilized the mutant.

Single cell proteomics microchip to profile immune function, with applications in stem cell biology, translational disease mechanism study and clinical therapeutics monitoring

In response to infection or tissue dysfunction, immune cells develop into highly heterogeneous repertoires with diverse functions. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. However, currently only 3-5 functional proteins can be measured from single cells. We developed a single cell functional proteomics approach that integrates a microchip platform with multiplex cell purification. This approach can quantitate 20 proteins from >5,000 phenotypically pure single cells simultaneously. With a 1-million fold miniaturization, the system can detect down to ~100 molecules and requires only ~104 cells. Single cell functional proteomic analysis finds broad applications in basic, translational and clinical studies. In the three studies conducted, it yielded critical insights for understanding clinical cancer immunotherapy, inflammatory bowel disease (IBD) mechanism and hematopoietic stem cell (HSC) biology.

To study phenotypically defined cell populations, single cell barcode microchips were coupled with upstream multiplex cell purification based on up to 11 parameters. Statistical algorithms were developed to process and model the high dimensional readouts. This analysis evaluates rare cells and is versatile for various cells and proteins. (1) We conducted an immune monitoring study of a phase 2 cancer cellular immunotherapy clinical trial that used T-cell receptor (TCR) transgenic T cells as major therapeutics to treat metastatic melanoma. We evaluated the functional proteome of 4 antigen-specific, phenotypically defined T cell populations from peripheral blood of 3 patients across 8 time points. (2) Natural killer (NK) cells can play a protective role in chronic inflammation and their surface receptor – killer immunoglobulin-like receptor (KIR) – has been identified as a risk factor of IBD. We compared the functional behavior of NK cells that had differential KIR expressions. These NK cells were retrieved from the blood of 12 patients with different genetic backgrounds. (3) HSCs are the progenitors of immune cells and are thought to have no immediate functional capacity against pathogen. However, recent studies identified expression of Toll-like receptors (TLRs) on HSCs. We studied the functional capacity of HSCs upon TLR activation. The comparison of HSCs from wild-type mice against those from genetics knock-out mouse models elucidates the responding signaling pathway.

In all three cases, we observed profound functional heterogeneity within phenotypically defined cells. Polyfunctional cells that conduct multiple functions also produce those proteins in large amounts. They dominate the immune response. In the cancer immunotherapy, the strong cytotoxic and antitumor functions from transgenic TCR T cells contributed to a ~30% tumor reduction immediately after the therapy. However, this infused immune response disappeared within 2-3 weeks. Later on, some patients gained a second antitumor response, consisted of the emergence of endogenous antitumor cytotoxic T cells and their production of multiple antitumor functions. These patients showed more effective long-term tumor control. In the IBD mechanism study, we noticed that, compared with others, NK cells expressing KIR2DL3 receptor secreted a large array of effector proteins, such as TNF-α, CCLs and CXCLs. The functions from these cells regulated disease-contributing cells and protected host tissues. Their existence correlated with IBD disease susceptibility. In the HSC study, the HSCs exhibited functional capacity by producing TNF-α, IL-6 and GM-CSF. TLR stimulation activated the NF-κB signaling in HSCs. Single cell functional proteome contains rich information that is independent from the genome and transcriptome. In all three cases, functional proteomic evaluation uncovered critical biological insights that would not be resolved otherwise. The integrated single cell functional proteomic analysis constructed a detail kinetic picture of the immune response that took place during the clinical cancer immunotherapy. It revealed concrete functional evidence that connected genetics to IBD disease susceptibility. Further, it provided predictors that correlated with clinical responses and pathogenic outcomes.

Noninterferometric measurement of lead zirconate titanate inverse piezoelectric extension

A noncontacting and noninterferometric depth discrimination technique, which is based on differential confocal microscopy, was used to measure the inverse piezoelectric extension of a piezoelectric ceramic lead zirconate titanate actuator. The response characteristics of the actuator with respect to the applied voltage, including displacement, linearity, and hysteresis, were obtained with nanometer measurement accuracy. Errors of the measurement have been analyzed. (C) 2001 Society of Photo-Optical Instrumentation Engineers.

Function of microRNA-146a and NF-κB in physiologic and pathologic hematopoiesis

During inflammation and infection, hematopoietic stem and progenitor cells (HSPCs) are stimulated to proliferate and differentiate into mature immune cells, especially of the myeloid lineage. MicroRNA-146a (miR-146a) is a critical negative regulator of inflammation. Deletion of the gene encoding miR-146a—expressed in all blood cell types—produces effects that appear as dysregulated inflammatory hematopoiesis, leading to a decline in the number and quality of hematopoietic stem cells (HSCs), excessive myeloproliferation, and, ultimately, to exhaustion of the HSCs and hematopoietic neoplasms. Six-week-old deleted mice are normal, with no effect on cell numbers, but by 4 months bone marrow hypercellularity can be seen, and by 8 months marrow exhaustion is becoming evident. The ability of HSCs to replenish the entire hematopoietic repertoire in a myelo-ablated mouse also declines precipitously as miR-146a-deficient mice age. In the absence of miR-146a, LPS-mediated serial inflammatory stimulation accelerates the effects of aging. This chronic inflammatory stress on HSCs in deleted mice involves a molecular axis consisting of upregulation of the signaling protein TRAF6 leading to excessive activity of the transcription factor NF-κB and overproduction of the cytokine IL-6. At the cellular level, transplant studies show that the defects are attributable to both an intrinsic problem in the miR-146a-deficient HSCs and extrinsic effects of miR-146a-deficient lymphocytes and non-hematopoietic cells. This study has identified a microRNA, miR-146a, to be a critical regulator of HSC homeostasis during chronic inflammatory challenge in mice and has provided a molecular connection between chronic inflammation and the development of bone marrow failure and myeloproliferative neoplasms. This may have implications for human hematopoietic malignancies, such as myelodysplastic syndrome, which frequently displays downregulated miR-146a expression.

A mathematical study of finite-amplitude rock-folding

The problem of the finite-amplitude folding of an isolated, linearly viscous layer under compression and imbedded in a medium of lower viscosity is treated theoretically by using a variational method to derive finite difference equations which are solved on a digital computer. The problem depends on a single physical parameter, the ratio of the fold wavelength, L, to the "dominant wavelength" of the infinitesimal-amplitude treatment, L_d. Therefore, the natural range of physical parameters is covered by the computation of three folds, with L/L_d = 0, 1, and 4.6, up to a maximum dip of 90°.

Significant differences in fold shape are found among the three folds; folds with higher L/L_d have sharper crests. Folds with L/L_d = 0 and L/L_d = 1 become fan folds at high amplitude. A description of the shape in terms of a harmonic analysis of inclination as a function of arc length shows this systematic variation with L/L_d and is relatively insensitive to the initial shape of the layer. This method of shape description is proposed as a convenient way of measuring the shape of natural folds.

The infinitesimal-amplitude treatment does not predict fold-shape development satisfactorily beyond a limb-dip of 5°. A proposed extension of the treatment continues the wavelength-selection mechanism of the infinitesimal treatment up to a limb-dip of 15°; after this stage the wavelength-selection mechanism no longer operates and fold shape is mainly determined by L/L_d and limb-dip.

Strain-rates and finite strains in the medium are calculated f or all stages of the L/L_d = 1 and L/L_d = 4.6 folds. At limb-dips greater than 45° the planes of maximum flattening and maximum flattening rat e show the characteristic orientation and fanning of axial-plane cleavage.

Using climate extension to assist coastal decision-makers with climate adaptation

Coastal managers need accessible, trusted, tailored resources to help them interpret climate information, identify vulnerabilities, and apply climate information to decisions about adaptation on regional and local levels. For decades, climate scientists have studied the impacts that short term natural climate variability and long term climate change will have on coastal systems. For example, recent estimates based on Intergovernmental Panel on Climate Change (IPCC) warming scenarios suggest that global sea levels may rise 0.5 to 1.4 meters above 1990 levels by 2100 (Rahmstorf 2007; Grinsted, Moore, and Jevrejeva 2009). Many low-lying coastal ecosystems and communities will experience more frequent salt water intrusion events, more frequent coastal flooding, and accelerated erosion rates before they experience significant inundation. These changes will affect the ways coastal managers make decisions, such as timing surface and groundwater withdrawals, replacing infrastructure, and planning for changing land use on local and regional levels. Despite the advantages, managers’ use of scientific information about climate variability and change remains limited in environmental decision-making (Dow and Carbone 2007). Traditional methods scientists use to disseminate climate information, like peer-reviewed journal articles and presentations at conferences, are inappropriate to fill decision-makers’ needs for applying accessible, relevant climate information to decision-making. General guides that help managers scope out vulnerabilities and risks are becoming more common; for example, Snover et al. (2007) outlines a basic process for local and state governments to assess climate change vulnerability and preparedness. However, there are few tools available to support more specific decision-making needs. A recent survey of coastal managers in California suggests that boundary institutions can help to fill the gaps between climate science and coastal decision-making community (Tribbia and Moser 2008). The National Sea Grant College Program, the National Oceanic and Atmospheric Administration's (NOAA) university-based program for supporting research and outreach on coastal resource use and conservation, is one such institution working to bridge these gaps through outreach. Over 80% of Sea Grant’s 32 programs are addressing climate issues, and over 60% of programs increased their climate outreach programming between 2006 and 2008 (National Sea Grant Office 2008). One way that Sea Grant is working to assist coastal decision-makers with using climate information is by developing effective methods for coastal climate extension. The purpose of this paper is to discuss climate extension methodologies on regional scales, using the Carolinas Coastal Climate Outreach Initiative (CCCOI) as an example of Sea Grant’s growing capacities for climate outreach and extension. (PDF contains 3 pages)

Improving aquaculture through increased fisheries extension research

The present study was conducted, as an attempt to disabuse minds of practicing fish farmers and also encourage prospective farmers who are of the opinion that fish culture is not as profitable as it is widely reported. The study was carried out in an abandoned concrete water fountain tank (20m super(2)) made primarily for recreational purposes. The tank was stocked initially with 125 post fingerlings (Heterobtranchus bidorsalis) bought at rate of N30 each. Cost of feeding was N3, 149.85. Gross and net profits for the passive 2- year culture stood at N27, 149.85 and N20, 000.00 respectively. The longest fish (L sub(max)) was 64.0 com TL while the smallest 41.5cm TL (64.8%L sub(max)) and weight 1.9kg (W sub(max)) and 0.5kg 26.3%W sub(max)). Weight and length data generated from the study were examined