New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site.

Although increasing evidence suggests that CTL are important to fight the development of some cancers, the frequency of detectable tumor-specific T cells is low in cancer patients, and these cells have generally poor functional capacities, compared with virus-specific CD8(+) T cells. The generation with a vaccine of potent CTL responses against tumor Ags therefore remains a major challenge. In the present study, ex vivo analyses of Melan-A-specific CD8(+) T cells following vaccination with Melan-A peptide and CpG oligodeoxynucleotides revealed the successful induction in the circulation of effective melanoma-specific T cells, i.e., with phenotypic and functional characteristics similar to those of CTL specific for immunodominant viral Ags. Nonetheless, the eventual impact on tumor development in vaccinated melanoma donors remained limited. The comprehensive study of vaccinated patient metastasis shows that vaccine-driven tumor-infiltrating lymphocytes, although activated, still differed in functional capacities compared with blood counterparts. This coincided with a significant increase of FoxP3(+) regulatory T cell activity within the tumor. The consistent induction of effective tumor-specific CD8(+) T cells in the circulation with a vaccine represents a major achievement; however, clinical benefit may not be achieved unless the tumor environment can be altered to enable CD8(+) T cell efficacy.

Acute painful diabetic neuropathy: an uncommon, remittent type of acute distal small fibre neuropathy.

INTRODUCTION: Acute painful diabetic neuropathy (APDN) is a distinctive diabetic polyneuropathy and consists of two subtypes: treatment-induced neuropathy (TIN) and diabetic neuropathic cachexia (DNC). The characteristics of APDN are (1.) the small-fibre involvement, (2.) occurrence paradoxically after short-term achievement of good glycaemia control, (3.) intense pain sensation and (4.) eventual recovery. In the face of current recommendations to achieve quickly glycaemic targets, it appears necessary to recognise and understand this neuropathy. METHODS AND RESULTS: Over 2009 to 2012, we reported four cases of APDN. Four patients (three males and one female) were identified and had a mean age at onset of TIN of 47.7 years (±6.99 years). Mean baseline HbA1c was 14.2% (±1.42) and 7.0% (±3.60) after treatment. Mean estimated time to correct HbA1c was 4.5 months (±3.82 months). Three patients presented with a mean time to symptom resolution of 12.7 months (±1.15 months). One patient had an initial normal electroneuromyogram (ENMG) despite the presence of neuropathic symptoms, and a second abnormal ENMG showing axonal and myelin neuropathy. One patient had a peroneal nerve biopsy showing loss of large myelinated fibres as well as unmyelinated fibres, and signs of microangiopathy. CONCLUSIONS: According to the current recommendations of promptly achieving glycaemic targets, it appears necessary to recognise and understand this neuropathy. Based on our observations and data from the literature we propose an algorithmic approach for differential diagnosis and therapeutic management of APDN patients.

Torre del Greco distrutta nel 1794 : [vue du site et du Vésuve en éruption] : [peinture]

Collectionneur : Lesouëf, Auguste (1829-1906)

Glenridge Campus Site

Dr. Deeks and Dr. Gibson admiring the Brock Unviersity sign at the Glenrdige Campus. Renovations to the old refigerator factory were only just underway at this time.

Decew Campus Site

Dr. Deeks and Dr. Gibson touring the recently acquired Decew Campus site along a stretch of Merrittville Highway in early 1964. The Sanatorium can be seen in the background.

Decew Campus Site

Dr. Deeks and Dr. Gibson examining the sign at the Decew Campus site along the stretch of Merrittville Highway just north of St. Davids Road. This photo was taken in March of 1964.

Decew Site Tour

Members of Brock University's Founders Committee and the Ontario Advisory Committee on Univesity Affairs tour the Decew site along with Premier John Robarts on June 5, 1963. Premier Robarts had just announced provincial assistance totalling $393,000 for the Brock University project. Pictured here from left to right are Dr. Deeks, Brock University Vice President; Premier Robarts; and James Allan, Provincial Treasurer.

Conformational analysis of antibody binding site using EDMA methods /

Euclidean distance matrix analysis (EDMA) methods are used to distinguish whether or not significant difference exists between conformational samples of antibody complementarity determining region (CDR) loops, isolated LI loop and LI in three-loop assembly (LI, L3 and H3) obtained from Monte Carlo simulation. After the significant difference is detected, the specific inter-Ca distance which contributes to the difference is identified using EDMA.The estimated and improved mean forms of the conformational samples of isolated LI loop and LI loop in three-loop assembly, CDR loops of antibody binding site, are described using EDMA and distance geometry (DGEOM). To the best of our knowledge, it is the first time the EDMA methods are used to analyze conformational samples of molecules obtained from Monte Carlo simulations. Therefore, validations of the EDMA methods using both positive control and negative control tests for the conformational samples of isolated LI loop and LI in three-loop assembly must be done. The EDMA-I bootstrap null hypothesis tests showed false positive results for the comparison of six samples of the isolated LI loop and true positive results for comparison of conformational samples of isolated LI loop and LI in three-loop assembly. The bootstrap confidence interval tests revealed true negative results for comparisons of six samples of the isolated LI loop, and false negative results for the conformational comparisons between isolated LI loop and LI in three-loop assembly. Different conformational sample sizes are further explored by combining the samples of isolated LI loop to increase the sample size, or by clustering the sample using self-organizing map (SOM) to narrow the conformational distribution of the samples being comparedmolecular conformations. However, there is no improvement made for both bootstrap null hypothesis and confidence interval tests. These results show that more work is required before EDMA methods can be used reliably as a method for comparison of samples obtained by Monte Carlo simulations.

A dimensional analysis of the benzylic hydroxylase active site in mortierella isabellina

The spatial limits of the active site in the benzylic hydroxylase enzyme of the fungus Mortierella isabellina were investigated. Several molecular probes were used in incubation experiments to determine the acceptability of each compound by this enzyme. The yields of benzylic alcohols provided information on the acceptability of the particular compound into the active site, and the enantiomeric excess values provided information on the "fit" of acceptable substrates. Measurements of the molecular models were made using Cambridge Scientific Computing Inc. CSC Chem 3D Plus modeling program. i The dimensional limits of the aromatic binding pocket of the benzylic hydroxylase were tested using suitably substituted ethyl benzenes. Both the depth (para substituted substrates) and width (ortho and meta substituted substrates) of this region were investigated, with results demonstrating absolute spatial limits in both directions in the plane of the aromatic ring of 7.3 Angstroms for the depth and 7.1 Angstroms for the width. A minimum requirement for the height of this region has also been established at 6.2 Angstroms. The region containing the active oxygen species was also investigated, using a series of alkylphenylmethanes and fused ring systems in indan, 1,2,3,4-tetrahydronaphthalene and benzocycloheptene substrates. A maximum distance of 6.9 Angstroms (including the 1.5 Angstroms from the phenyl substituent to the active center of the heme prosthetic group of the enzyme) has been established extending directly in ii front of the aromatic binding pocket. The other dimensions in this region of the benzylic hydroxylase active site will require further investigation to establish maximum allowable values. An explanation of the stereochemical distributions in the obtained products has also been put forth that correlates well with the experimental observations.

The relationship between stem-form, stand-closure and site -conditions : the influence of environmental conditions on tree allometry and forest structure in west-central Alberta

Changes in the configuration of a tree stern result insignificant differences in its total volume and in the proportion of that volume that is merchantable timber. Tree allometry, as represented by stem-fo~, is the result of the vertical force of gravity and the horizontal force of wind. The effect of wind force is demonstrated in the relationship between stem-form, standclosure and site-conditions. An increase in wind force on the individual tree due to a decrease in stand density should produce a more tapered tree. The density of the stand is determined by the conditions that the trees are growing under. The ability of the tree to respond to increased wind force may also be a function of these conditions . This stem-form/stand-closure/site-conditions relationship was examined using a pre-existing database from westcentral Alberta. This database consisted of environmental, vegetation, soils and timber data covering a wide range of sites. There were 653 sample trees with 82 variables that formed the basis of the analysis. There were eight tree species consisting of Pinus contorta, Picea mariana, Picea engelmannii x glauca, Abies lasiocarpa, Larix laricina, Populus tremuloides, Betula papyrifera and Populus balsamifera plus a comprehensive all-species data set. As the actual conformation of the stern is very individual, stem-fo~was represented by the diameter at breast height to total height r~tio. The four stand-closure variables, crown closure, total basal area, total volume and total number of stems were reduced to total basal area and total number of stems utilizing a bivariate correlation matrix by species. Site-conditions were subdivided into macro, meso and micro variables and reduced in number 3 using cross-tabulations, bivariate correlation and principal components analysis as screening tools. The stem-fo~/stand-closure relationship was examined using bivariate correlation coefficients for stem-fo~ with total number of stems and stem-fo~ with total basal area. The stem-fo~/site-conditions and the stand-closure/site- conditions relationships were examined using multiple correlation coefficients. The stem-form/stand-closure/site-conditions relationship was examined using multiple correlation coefficients in separate analyses for both total number of stems and total basal area. An increase in stand-closure produced a decrease in stem-form for both total number of stems and total basal area for most species. There was a significant relationship between stem-form and site-conditions and between stand-closure and site-conditions for both total number of stems and total basal area for most species. There was a significant relationship between the stemform and site-conditions, including the stand-closure, for most species; total number of stems was involved independently of the site-conditions in the prediction of stem-form and total basal area was not. Larix laricina and Betula papyrifera were the exceptions to the trends observed with most species. The influence of both stand-closure (total number of stems in particular) and site-conditions (elevation in particular) suggest that forest management practices should include these- ecological parameters in determining appropriate restocking levels.

Orientation of Non-Native 2-Monosubstituted and 2,3-Disubstituted 1,4-Naphthoquinones in the A1 binding site of PSI and the effect on the rate of electron transfer : an electron paramagnetic resonance spectroscopy study

The proce-ss ofoxygenic photosynthesis is vital to life on Earth. the central event in photosynthesis is light induced electron transfer that converts light into energy for growth. Ofparticular significance is the membrane bound multisubunit protein known as Photosystem I (PSI). PSI is a reaction centre that is responsible for the transfer of electrons across the membrane to reduce NADP+ to NADPH. The recent publication ofa high resolution X-ray structure of PSI has shown new information about the structure, in particular the electron transfer cofactors, which allows us to study it in more detail. In PSI, the secondary acceptor is crucial for forward electron transfer. In this thesis, the effect of removing the native acceptor phylloquinone and replacing it with a series of structurally related quinones was investigated via transient electron paramagnetic resonance (EPR) experiments. The orientation of non native quinones in the binding site and their ability to function in the electron transfer process was determined. It was found that PSI will readily accept alkyl naphthoquinones and anthraquinone. Q band EPR experiments revealed that the non-native quinones are incorporated into the binding site with the same orientation of the headgroup as in the native system. X band EPR spectra and deuteration experiments indicate that monosubstituted naphthoquinones are bound to the Al site with their side group in the position occupied by the methyl group in native PSI (meta to the hydrogen bonded carbonyl oxygen). X band EPR experiments show that 2, 3- disubstituted methyl naphthoquinones are also incorporated into the Al site in the same orientation as phylloquinone, even with the presence of a halogen- or sulfur-containing side chain in the position normally occupied by the phytyl tail ofphylloquinone. The exception to this is 2-bromo-3-methyl --.- _. -. - -- - - 4 _._ _ _ - _ _ naphthoquinone which has a poorly resolved spectrum, making determination of the orientation difficuh. All of the non-native quinones studied act as efficient electron acceptors. However, forward electron transfer past the quinone could only be demonstrated for anthraquinone, which has a more negative midpoint potential than phylloquinone. In the case of anthraquinone, an increased rate of forward electron transfer compared to native PSI was found. From these results we can conclude that the rate ofelectron transfer from Al to Fx in native PSI lies in the normal region ofthe Marcus Curve.

What gets plans off the shelf? : a multi-site case study of the factors influencing municipal recreation plan implementation

Municipalities that engage in recreation planning have the potential to use their resources more effectively. However, successful planning means getting the plan off the shelf and implemented. This study investigated the factors that influenced municipal recreation plan implementation in three municipalities. Interviews were conducted with eleven key informants (recreation directors, planning consultants, a city councillor, and members of plan steering committees). The findings of this study suggested that because the implementation of recreation plans occurs in a highly political environment, recreation professionals will need effective strategies to get their plans implemented and that implementation can be facilitated by developing or expanding strategies that: (l) build the power of the recreation department within the municipal government structure; (2) build support for recreation within the local community; and (3) build the political and organizational capacity in the recreation department.

Delineation of within-site terroir effects using soil and vine water measurement. Investigation of Cabernet Franc

. The influence of vine water status was studied in commercial vineyard blocks of Vilis vinifera L. cv. Cabernet Franc in Niagara Peninsula, Ontario from 2005 to 2007. Vine performance, fruit composition and vine size of non-irrigated grapevines were compared within ten vineyard blocks containing different soil and vine water status. Results showed that within each vineyard block water status zones could be identified on GIS-generated maps using leaf water potential and soil moisture measurements. Some yield and fruit composition variables correlated with the intensity of vine water status. Chemical and descriptive sensory analysis was performed on nine (2005) and eight (2006) pairs of experimental wines to illustrate differences between wines made from high and low water status winegrapes at each vineyard block. Twelve trained judges evaluated six aroma and flavor (red fruit, black cherry, black current, black pepper, bell pepper, and green bean), thr~e mouthfeel (astringency, bitterness and acidity) sensory attributes as well as color intensity. Each pair of high and low water status wine was compared using t-test. In 2005, low water status (L WS) wines from Buis, Harbour Estate, Henry of Pelham (HOP), and Vieni had higher color intensity; those form Chateau des Charmes (CDC) had high black cherry flavor; those at RiefEstates were high in red fruit flavor and at those from George site was high in red fruit aroma. In 2006, low water status (L WS) wines from George, Cave Spring and Morrison sites were high in color intensity. L WS wines from CDC, George and Morrison were more intense in black cherry aroma; LWS wines from Hernder site were high in red fruit aroma and flavor. No significant differences were found from one year to the next between the wines produced from the same vineyard, indicating that the attributes of these wines were maintained almost constant despite markedly different conditions in 2005 and 2006 vintages. Partial ii Least Square (PLS) analysis showed that leaf \}' was associated with red fruit aroma and flavor, berry and wine color intensity, total phenols, Brix and anthocyanins while soil moisture was explained with acidity, green bean aroma and flavor as well as bell pepper aroma and flavor. In another study chemical and descriptive sensory analysis was conducted on nine (2005) and eight (2006) medium water status (MWS) experimental wines to illustrate differences that might support the sub-appellation system in Niagara. The judges evaluated the same aroma, flavor, and mouthfeel sensory attributes as well as color intensity. Data were analyzed using analysis of variance (ANOVA), principal component analysis (PCA) and discriminate analysis (DA). ANOV A of sensory data showed regional differences for all sensory attributes. In 2005, wines from CDC, HOP, and Hemder sites showed highest. r ed fruit aroma and flavor. Lakeshore and Niagara River sites (Harbour, Reif, George, and Buis) wines showed higher bell pepper and green bean aroma and flavor due to proximity to the large bodies of water and less heat unit accumulation. In 2006, all sensory attributes except black pepper aroma were different. PCA revealed that wines from HOP and CDC sites were higher in red fruit, black currant and black cherry aroma and flavor as well as black pepper flavor, while wines from Hemder, Morrison and George sites were high in green bean aroma and flavor. ANOV A of chemical data in 2005 indicated that hue, color intensity, and titratable acidity (TA) were different across the sites, while in 2006, hue, color intensity and ethanol were different across the sites. These data indicate that there is the likelihood of substantial chemical and sensory differences between clusters of sub-appellations within the Niagara Peninsula iii

The nesting biology of Ceratina (Hymenoptera: Apidae) in the Niagara Region : new species, nest site selection and parasitism

One of the most common bee genera in the Niagara Region, the genus Ceratina (Hymenoptera: Apidae) is composed of four species, C. dupla, C. calcarata, the very rare C. strenua, and a previously unknown species provisionally named C. near dupla. The primary goal of this thesis was to investigate how these closely related species coexist with one another in the Niagara ~ee community. The first necessary step was to describe and compare the nesting biologies and life histories of the three most common species, C. dupla, C. calcarata and the new C. near dupla, which was conducted in 2008 via nest collections and pan trapping. Ceratina dupla and C. calcarata were common, each comprising 49% of the population, while C. near dupla was rare, comprising only 2% of the population. Ceratina dupla and C. near dupla both nested more commonly in teasel (Dipsacus sp.) in the sun, occasionally in raspberry (Rubus sp.) in the shade, and never in shady sumac (Rhus sp.), while C. calcarata nested most commonly in raspberry and sumac (shaded) and occasionally in teasel (sunny). Ceratina near dupla differed from both C. dupla and C. calcarata in that it appeared to be partially bivoltine, with some females founding nests very early and then again very late in the season. To examine the interactions and possible competition for nests that may be taking place between C. dupla and C. calcarata, a nest choice experiment was conducted in 2009. This experiment allowed both species to choose among twigs from all three substrates in the sun and in the shade. I then compared the results from 2008 (where bees chose from what was available), to where they nested when given all options (2009 experiment). Both C. dupla and C. calcarata had the same preferences for microhabitat and nest substrate in 2009, that being raspberry and sumac twigs in the sun. As that microhabitat and nest substrate combination is extremely rare in nature, both species must make a choice. In nature Ceratina dupla nests more often in the preferred microhabitat (sun), while C. calcarata nests in the preferred substrate (raspberry). Nesting in the shade also leads to smaller clutch sizes, higher parasitism and lower numbers of live brood in C. calcarata, suggesting that C. dupla may be outcompeting C. calcarata for the sunny nesting sites. The development and host preferences of Ceratina parasitoids were also examined. Ceratina species in Niagara were parasitized by no less than eight species of arthropod. Six of these were wasps from the superfamily Chalcidoidea (Hymenoptera), one was a wasp from the family Ichneumonidae (Hymenoptera) and one was a physogastric mite from the family Pyemotidae (Acari). Parasites shared a wide range of developmental strategies, from ichneumonid larvae that needed to consume multiple Ceratina immatures to complete development, to the species from the Eulophidae (Baryscapus) and Encyrtidae (Coelopencyrtus), in which multiple individuals completed development inside a single Ceratina host. Biological data on parasitoids is scarce in the scientific literature, and this Chapter documents these interactions for future research.