High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment

Rapid imaging by antitumor antibodies has been limited by the prolonged targeting kinetics and clearance of labeled whole antibodies. Genetically engineered fragments with rapid access and high retention in tumor tissue combined with rapid blood clearance are suitable for labeling with short-lived radionuclides, including positron-emitting isotopes for positron-emission tomography (PET). An engineered fragment was developed from the high-affinity anticarcinoembryonic antigen (CEA) monoclonal antibody T84.66. This single-chain variable fragment (Fv)-CH3, or minibody, was produced as a bivalent 80 kDa dimer. The macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-N,N′,N′′, N′′′-tetraacetic acid (DOTA) was conjugated to the anti-CEA minibody for labeling with copper-64, a positron-emitting radionuclide (t1/2 = 12.7 h). In vivo distribution was evaluated in athymic mice bearing paired LS174T human colon carcinoma (CEA positive) and C6 rat glioma (CEA negative) xenografts. Five hours after injection with 64Cu-DOTA-minibody, microPET imaging showed high uptake in CEA-positive tumor (17.9% injected dose per gram ± 3.79) compared with control tumor (6.0% injected dose per gram ± 1.0). In addition, significant uptake was seen in liver, with low uptake in other tissues. Average target/background ratios relative to neighboring tissue were 3–4:1. Engineered antibody fragments labeled with positron-emitting isotopes such as copper-64 provide a new class of agents for PET imaging of tumors.

Prevalence of AmpC β-lactamase among Gram-negative bacteria recovered from clinical specimens in Benin City, Nigeria

Purpose: Infections caused by AmpC-positive bacteria results in high patient morbidity and mortality making their detection clinically important as they cannot be detected in routine susceptibility testing. This study aim to determine the prevalence of AmpC β-lactamase among Gram negative bacteria recovered from clinical specimens in Benin City, Nigeria. Methods: A total of 256 consecutive and non-repetitive Gram negative bacteria were recovered from various clinical specimens. The prevalence of AmpC β-lactamase was determined using a combination of disc antagonism test and cefoxitin-cloxacillin inhibition test. Disc susceptibility test was performed on all isolates using standard techniques. Results: Cefoxitin-cloxacillin inhibition test detected more AmpC β-lactamase than other tests. The prevalence of AmpC β-lactamase did not differ significantly between both genders and between inpatients and out-patients (p>0.05). Isolates recovered from sputum had significantly higher prevalence of AmpC β-lactamase producers compared with isolates from other clinical specimens (p=0.0484). The prevalence of AmpC production was significantly higher among isolates of Pseudomonas aeruginosa than other isolates (p = 0.0085). Isolates that produced AmpC β-lactamase were more susceptible to the test cephalosoprins. Conclusion: An overall prevalence of AmpC β-lactamase (15.23 %) was observed in this study. Pseudomonas aeruginosa was the most prevalent producer of AmpC enzymes. Prudent use of antibiotics is advocated.

Streptomyces caldifontis sp. nov., isolated from a hot water spring of Tatta Pani, Kotli, Pakistan

A Gram-staining positive, non-motile, rod-shaped, catalase positive and oxidase negative bacterium, designated NCCP-1331(T), was isolated from a hot water spring soil collected from Tatta Pani, Kotli, Azad Jammu and Kashmir, Pakistan. The isolate grew at a temperature range of 18-40 °C (optimum 30 °C), pH 6.0-9.0 (optimum 7.0) and with 0-6 % NaCl (optimum 2 % NaCl (w/v)). The phylogenetic analysis based on 16S rRNA gene sequence revealed that strain NCCP-1331(T) belonged to the genus Streptomyces and is closely related to Streptomyces brevispora BK160(T) with 97.9 % nucleotide similarity, followed by Streptomyces drosdowiczii NRRL B-24297(T) with 97.8 % nucleotide similarity. The DNA-DNA relatedness values of strain NCCP-1331(T) with S. brevispora KACC 21093(T) and S. drosdowiczii CBMAI 0498(T) were 42.7 and 34.7 %, respectively. LL-DAP was detected as diagnostic amino acid along with alanine, glycine, leucine and glutamic acid. The isolate contained MK-9(H8) as the predominant menaquinone. Major polar lipids detected in NCCP-1331(T) were phosphatidylethanolamine, phosphatidylinositol and unidentified phospholipids. Major fatty acids were iso-C16: 0, summed feature 8 (18:1 ω7c/18:1 ω6c), anteiso-C15:0 and C16:0. The genomic DNA G + C content was 69.8 mol %. On the basis of phylogenetic, phenotypic and chemotaxonomic analysis, it is concluded that strain NCCP-1331(T) represents a novel species of the genus Streptomyces, for which the name Streptomyces caldifontis sp. nov. is proposed. The type strain is NCCP-1331(T) (=KCTC 39537(T) = CPCC 204147(T)).

Extreme sports as a facilitator of ecocentricity and positive life changes

Extreme sports and extreme sports participants have been most commonly explored from a negative perspective, for example the 'need to take unnecessary risks'. This study reports on findings that indicate a more positive experience. A phenomenological method was used via unstructured interviews with 15 extreme sports participants and other first hand accounts. The extreme sports included B.A.S.E. jumping, big wave surfing, extreme skiing, waterfall kayaking, extreme mountaineering and solo rope-free climbing. Results indicate that participating in activities that involve a real chance of death, fear and the realisation that nature in its extreme is far greater and more powerful than humanity triggers positive life changes, and an eco-centric standpoint.

Extreme Sports: A positive transformation in courage and humility

Extreme sports and extreme sports participants have been most commonly explored from a negative perspective, for example the “need to take unnecessary risks.” This study explored what can be learned from extreme sports about courage and humility - two positive psychology constructs. A phenomenological method was used via unstructured interviews with 15 extreme sports participants and other first hand accounts. The extreme sports included B.A.S.E. jumping, big wave surfing, extreme skiing, waterfall kayaking, extreme mountaineering and solo rope-free climbing. Results indicate that humility and courage can be deliberately sought out by participating in activities that involve a real chance of death, fear and the realisation that nature in its extreme is far greater and more powerful than humanity.

Positive development

net sustainability. At best they reduce relative resource consumption. They still consume vast quantities of materials, energy, water and ecosystems during construction. Moreover, green buildings replace land and ecosystems with structures that, at the very best, only 'mimic' ecosystems<'). Mimicking nature is little compensation when we have lost a third of species that are integral parts of our life support system. Already, development has exceeded the Earth's ecological carrying capacity, so even 'restorative' design is not enough. Urban areas must be retrofitted to increase net bioregional carrying capacity - just to support existing or reduced population levels in cities. The eco-retrofitting of our built environment is therefore an essential precondition of achieving a sustainable society. But we need to eco-retrofit cities in ways that increase net sustainability, not just relative efficiency.

Space frame walls : facilitating positive development

This paper reports on progress in developing new design and measurement concepts, and translating these concepts into practical applications. This research addresses gaps in ‘best practice’ green building, and is aimed ultimately at replacing green buildings with sustainable urban environments. Building on the author’s previously articulated concepts of Design for Eco-services and Positive Development, this research will demonstrate how to eco-retrofit cities so that they reverse the negative impacts of past design and generate net positive ecological impacts, at no extra cost. In contrast to ‘restorative’ design,this means increasing ecological carrying capacity and natural and social capital through built environment design. Some exemplars for facilitating Positive development will be presented in this talk,such as Green Scaffolding for retrofits, and Green Space Walls for new construction. These structures have been designed to grow and change over time, be easily deconstructed, and entail little waste. The frames support mini-ecospheres that provide a wide range of ecosystem services and biodiversity habitats, as well as heating, cooling and ventilating. In combination, the modules serve to improve human and environmental health. Current work is focused on developing a range of such space frame walls, optimised through an innovative marriage of eco-logical design and virtual modelling.

The relationship between significant others' positive and negative statements, self-talk and self-esteem

This study investigated the effect of self-talk in mediating between positive and negative statements made by significant others and self-esteem with children in grades 3 to 7. Students completed questionnaires on the frequency of positive and negative statements from parents, teachers, and peers. Findings suggest that self-talk does mediate between significant others' statements and children's self-esteem.