Agricultural Nonpoint Source Pollution Control in Theory and Practice

The theory of efficient policy instruments for agricultural pollution control has been evolving. Some new developments suggest that policies using financial incentives to encourage desirable farming practices are superior to those focusing on runoff directly or restrictions on farming practices. However, the theoretical models used to derive such results make assumptions about conditions that may not hold. As a result, implementation of the findings of such models is not necessarily routine. This article attempts to summarize these studies and interpret their implications for agricultural nonpoint source pollution control for the Chesapeake Bay.Environmental Economics and Policy, Research Methods/ Statistical Methods, Resource /Energy Economics and Policy,

Experimentally induced musculoskeletal pain : a tool for understanding chronic pain

Pain is a complex modality which can arise from a plethora of sources, both internal and external, which, under normal physiological conditions, is an essential aspect of life for the identification of injury to an individual. However, in a subset of the population suffering from chronic pain, the distinction between painful and non-painful sensations can become askew, resulting in the formation of allodynia, hyperalgesia and other manifestations of pain-hypersensitivity. Within this thesis, the utilisation and characterisation of both acute and prolonged experimental models of musculoskeletal pain were undertaken to examine the regional distribution and evoked perceptual changes of muscle pain. The examination of the differential response between acute and prolonged pain may aid in the identification of the neural mechanisms which underpin the transition from acute to chronic pain in patients. Across both pain conditions, an ability for normally non-perceptual stimuli to evoke a hyperalgesic response is also reported, which may impact our understanding of clinical chronic pain. Furthermore, the potential of the drug minocycline to reduce somatosensory hypersensitivities associated with prolonged muscle pain was also examined

Modulation of muscle pain is not somatotopically restricted : an experimental model using concurrent hypertonic-normal saline infusions in humans

We have previously shown that during muscle pain induced by infusion of hypertonic saline (HS), concurrent application of vibration and gentle brushing to overlying and adjacent skin regions increases the overall pain. In the current study, we focused on muscle-muscle interactions and tested whether HS-induced muscle pain can be modulated by innocuous/sub-perceptual stimulation of adjacent, contralateral, and remote muscles. Psychophysical observations were made in 23 healthy participants. HS (5%) was infused into a forearm muscle (flexor carpi ulnaris) to produce a stable baseline pain. In separate experiments, in each of the three test locations (n = 10 per site)—ipsilateral hand (abductor digiti minimi), contralateral forearm (flexor carpi ulnaris), and contralateral leg (tibialis anterior)—50 μl of 0.9% normal saline (NS) was infused (in triplicate) before, during, and upon cessation of HS-induced muscle pain in the forearm. In the absence of background pain, the infusion of NS was imperceptible to all participants. In the presence of HS-induced pain in the forearm, the concurrent infusion of NS into the ipsilateral hand, contralateral forearm, and contralateral leg increased the overall pain by 16, 12, and 15%, respectively. These effects were significant, reproducible, and time-locked to NS infusions. Further, the NS-evoked increase in pain was almost always ascribed to the forearm where HS was infused with no discernible percept attributed to the sites of NS infusion. Based on these observations, we conclude that intramuscular infusion of HS results in muscle hyperalgesia to sub-perceptual stimulation of muscle afferents in a somatotopically unrestricted manner, indicating the involvement of a central (likely supra-spinal) mechanism

Impact ionisation electroluminescence in planar GaAs-based heterostructure Gunn diodes:Spatial distribution and impact of doping nonuniformities

When biased in the negative differential resistance regime, electroluminescence (EL) is emitted from planar GaAs heterostructure Gunn diodes. This EL is due to the recombination of electrons in the device channel with holes that are generated by impact ionisation when the Gunn domains reach the anode edge. The EL forms non-uniform patterns whose intensity shows short-range intensity variations in the direction parallel to the contacts and decreases along the device channel towards the cathode. This paper employs Monte Carlo models, in conjunction with the experimental data, to analyse these non-uniform EL patterns and to study the carrier dynamics responsible for them. It is found that the short-range lateral (i.e., parallel to the device contacts) EL patterns are probably due to non-uniformities in the doping of the anode contact, illustrating the usefulness of EL analysis on the detection of such inhomogeneities. The overall decreasing EL intensity towards the anode is also discussed in terms of the interaction of holes with the time-dependent electric field due to the transit of the Gunn domains. Due to their lower relative mobility and the low electric field outside of the Gunn domain, freshly generated holes remain close to the anode until the arrival of a new domain accelerates them towards the cathode. When the average over the transit of several Gunn domains is considered, this results in a higher hole density, and hence a higher EL intensity, next to the anode

Calbindin-D28k gene expression in the developing mouse kidney

Calbindin-D28k gene expression in the developing mouse kidney. Calbindin-D28k appears in the metanephric kidney during embryogenesis. We studied the temporal appearance and spatial distribution of calbindin-D28k mRNA in the developing kidneys of 12-day fetal through 21-day postnatal mice by in situ hybridization. 35S-UTP-labeled antisense (cRNA) probe to calbindin-D28k mRNA hybridized to the ureteric buds of 12-day embryos, whereas adjacent metanephrogenic tissue was unlabeled. By embryonic day 13, Y-shaped bodies of “advancing” ureteric buds were labeled intensely. In 16-day embryos, ampullae of ureteric buds were located immediately beneath the renal capsule and labeled strongly, in contrast to metanephric tubules and S-shaped bodies. The former were unlabeled and the latter were labeled only at points of contact with the ampullae. Subsequently, the ampullae of the metanephric ureteric buds hybridized with the cRNA probe, and from the 18th embryonic to the 21st postnatal day, this labeling was intense. The cRNA probe did not hybridize with the renal vesicles, proximal tubules, or tubular segments of Henle's loop derived from nephrogenic blastema, but it did label distal nephron segments. By the 21st postnatal day, collecting ducts and ureter no longer were labeled. In conclusion, calbindin-D28k mRNA is present in the developing mouse kidney, and its distribution during nephrogenesis is identical to that of calbindin-D28k per se. Collectively, these findings show that the calbindin-D28k gene is transcribed and its message is translated by the cells of the ureteric bud during the initial stage of renal morphogenesis

Intestinal epithelial replacement by transplantation of cultured murine and human cells into the small intestine.

Adult intestinal epithelial stem cells are a promising resource for treatment of intestinal epithelial disorders that cause intestinal failure and for intestinal tissue engineering. We developed two different animal models to study the implantation of cultured murine and human intestinal epithelial cells in the less differentiated "spheroid" state and the more differentiated "enteroid" state into the denuded small intestine of mice. Engraftment of donor cells could not be achieved while the recipient intestine remained in continuity. However, we were able to demonstrate successful implantation of murine and human epithelial cells when the graft segment was in a bypassed loop of jejunum. Implantation of donor cells occurred in a random fashion in villus and crypt areas. Engraftment was observed in 75% of recipients for murine and 36% of recipients for human cells. Engrafted spheroid cells differentiated into the full complement of intestinal epithelial cells. These findings demonstrate for the first time successful engraftment into the small bowel which is optimized in a bypassed loop surgical model

Exclusion of Polymorphisms in Carnosinase Genes (CNDP1 and CNDP2) as a Cause of Diabetic Nephropathy in Type 1 Diabetes: Results of Large Case-Control and Follow-Up Studies

OBJECTIVES— Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chromosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from four to seven) in the leader peptide of the carnosinase precursor. The frequency of subjects homozygous for the five leucines was higher in control subjects than in case subjects in studies focusing on type 2 diabetic patients. To test whether this finding can be extended to type 1 diabetic patients, we carried out a comprehensive study on association between diabetic nephropathy and the D18S880 microsatellite and 21 additional SNPs that tagged the genomic region containing CNDP1 and CNDP2

Heat Shock Protein-90 Inhibitors Enhance Antigen Expression on Melanomas and Increase T Cell Recognition of Tumor Cells

In an effort to enhance antigen-specific T cell recognition of cancer cells, we have examined numerous modulators of antigen-expression. In this report we demonstrate that twelve different Hsp90 inhibitors (iHsp90) share the ability to increase the expression of differentiation antigens and MHC Class I antigens. These iHsp90 are active in several molecular and cellular assays on a series of tumor cell lines, including eleven human melanomas, a murine B16 melanoma, and two human glioma-derived cell lines. Intra-cytoplasmic antibody staining showed that all of the tested iHsp90 increased expression of the melanocyte differentiation antigens Melan-A/MART-1, gp100, and TRP-2, as well as MHC Class I. The gliomas showed enhanced gp100 and MHC staining. Quantitative analysis of mRNA levels showed a parallel increase in message transcription, and a reporter assay shows induction of promoter activity for Melan-A/MART-1 gene. In addition, iHsp90 increased recognition of tumor cells by T cells specific for Melan-A/MART-1. In contrast to direct Hsp90 client proteins, the increased levels of full-length differentiation antigens that result from iHsp90 treatment are most likely the result of transcriptional activation of their encoding genes. In combination, these results suggest that iHsp90 improve recognition of tumor cells by T cells specific for a melanoma-associated antigen as a result of increasing the expressed intracellular antigen pool available for processing and presentation by MHC Class I, along with increased levels of MHC Class I itself. As these Hsp90 inhibitors do not interfere with T cell function, they could have potential for use in immunotherapy of cancer

Myo4p is a monomeric myosin with motility uniquely adapted to transport mRNA

The yeast Saccharomyces cerevisiae uses two class V myosins to transport cellular material into the bud: Myo2p moves secretory vesicles and organelles, whereas Myo4p transports mRNA. To understand how Myo2p and Myo4p are adapted to transport physically distinct cargos, we characterize Myo2p and Myo4p in yeast extracts, purify active Myo2p and Myo4p from yeast lysates, and analyze their motility. We find several striking differences between Myo2p and Myo4p. First, Myo2p forms a dimer, whereas Myo4p is a monomer. Second, Myo4p generates higher actin filament velocity at lower motor density. Third, single molecules of Myo2p are weakly processive, whereas individual Myo4p motors are nonprocessive. Finally, Myo4p self-assembles into multi-motor complexes capable of processive motility. We show that the unique motility of Myo4p is not due to its motor domain and that the motor domain of Myo2p can transport ASH1 mRNA in vivo. Our results suggest that the oligomeric state of Myo4p is important for its motility and ability to transport mRNA