Parametric Analysis for Monitoring 2D Kinetics of Receptor-Ligand binding

Thermal fluctuation approach is widely used to monitor association kinetics of surface-bound receptor-ligand interactions. Various protocols such as sliding standard deviation (SD) analysis (SSA) and Page's test analysis (PTA) have been used to estimate two-dimensional (2D) kinetic rates from the time course of displacement of molecular carrier. In the current work, we compared the estimations from both SSA and modified PTA using measured data from an optical trap assay and simulated data from a random number generator. Our results indicated that both SSA and PTA were reliable in estimating 2D kinetic rates. Parametric analysis also demonstrated that such the estimations were sensitive to parameters such as sampling rate, sliding window size, and threshold. These results furthered the understandings in quantifying the biophysics of receptor-ligand interactions.

Technological status and development prospects of small-scale fishing crafts in Nigerian coastal water

A study of fishing crafts was conducted in some coastal states of Nigeria to elucidate findings on the existing crafts as the baseline for further developments. Based on the technical designs, three types of fishing crafts were identified; planked, dug-out and half dug-out canoes. The planked canoes have the largest cubic number and dug-out canoes the least. At loadwater line, the ratio of freeboard to draft was 2 : 1 for planked canoes, indicating reserved buoyancy. Trim of planked canoe is by stern; the beam-length ratio for dug-out canoes showed high drag. Most of the sea-going canoes have U-shaped bottom hull profile capable of withstanding the rigours of surf landing and displayed good stability against longitudinal water wave. Gunwale and thwarts provided respectively the longitudinal and transverse strength of planked and half dug-out canoes. With its characteristics 'weight low down' construction, planked canoe represent the climax of small scale fishing crafts developments in Nigerian coastal waters. It's only draw back is durability. Further improvement in this canoe should be aimed at increasing the hull size and stiffness, water tightness of deck by coating, caulking, fastening, increasing level of motorization and installation of deck working equipments. Experimental design and use of fibre glass, aluminium and ferrocement hulls, together with improved planked canoe is highly advocated

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.

Radioaktives Cäsium im Fisch der Barentssee weiterhin abnehmend

A decrease of 137Cs concentration in cod flesh from Barents Sea is shown by six years random sampling. This reduction runs parallel to reduced emissions from the nuclear fuel reprocessing plant Sellafield (Great Britain). It must be emphasized that even the highest values from 1992 are lower than comparable ones from the North Sea and from the Baltic. Although there is no increase of the radiation dose on people by consuming these fishes further monitoring should not be stopped. Potential risk arises from radioactive wastes of the russian nuclear navy in their coastal area. Obviously a safe storage seams almost too expensive.

Coastal brownfields and adaptation to climate change: Discussions on potential hazards from contaminated groundwater displacement due to saltwater incursion

Toxic-waste associated with coastal brownfield sites can pose serious risks to human and environmental health. In light of anticipated sea-level rise (SLR) due to global climate change, coastal brownfields require heightened attention. The primary intent of this study is to pose questions and encourage discussion of this problem among policy makers. Impacts from SLR on coastal zones are examined within a brownfield policy framework and, current coastal brownfield policy discussions with respect to SLR are also examined. (PDF contains 4 pages)