Terahertz detection of illegal objects

This paper describes the main parameters - contrast, spatial resolution, and thermal sensitivity - which define the performance of any stand-off imaging system. The origin of the signature for both metal and dielectric objects hidden under clothing in the frequency range from 100 GHz to 500 GHz is discussed. At 100 GHz the signature is dominated by reflection whilst at 500 GHz it is dominated by emission. A 94-GHz-passive millimetre-wave imaging system has been designed and fabricated to image objects under clothing. This imager is based on a Schmidt camera folded using polarisation techniques.

Burkholderia cenocepacia requires the RpoN sigma factor for biofilm formation and intracellular trafficking within macrophages

Chronic respiratory infections by Burkholderia cenocepacia in cystic fibrosis patients are associated with increased morbidity and mortality, but virulence factors determining the persistence of the infection in the airways are not well characterized. Using a chronic pulmonary infection model, we previously identified an attenuated mutant with an insertion in a gene encoding an RpoN activator protein, suggesting that RpoN and/or components of the RpoN regulon play a role in B. cenocepacia virulence. In this study, we demonstrate that a functional rpoN gene is required for bacterial motility and biofilm formation in B. cenocepacia K56-2. Unlike other bacteria, RpoN does not control flagellar biosynthesis, as evidenced by the presence of flagella in the rpoN mutant. We also demonstrate that, in macrophages, the rpoN mutant is rapidly trafficked to lysosomes while intracellular wild-type B. cenocepacia localizes in bacterium-containing vacuoles that exhibit a pronounced delay in phagolysosomal fusion. Rapid trafficking to the lysosomes is also associated with the release of red fluorescent protein into the vacuolar lumen, indicating loss of bacterial cell envelope integrity. Although a role for RpoN in motility and biofilm formation has been previously established, this study is the first demonstration that the RpoN regulon in B. cenocepacia is involved in delaying phagolysosomal fusion, thereby prolonging bacterial intracellular survival within macrophages.

Diagnostic accuracy and clinical management by realtime teledermatology. Results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial

Diagnostic accuracy and management recommendations of realtime teledermatology consultations using low-cost telemedicine equipment were evaluated. Patients were seen by a dermatologist over a video-link and a diagnosis and treatment plan were recorded. This was followed by a face-to-face consultation on the same day to confirm the earlier diagnosis and management plan. A total of 351 patients with 427 diagnoses participated. Sixty-seven per cent of the diagnoses made over the video-link agreed with the face-to-face diagnosis. Clinical management plans were recorded for 214 patients with 252 diagnoses. For this cohort, 44% of the patients were seen by the same dermatologist at both consultations, while 56% were seen by a different dermatologist. In 64% of cases the same management plan was recommended at both consultations; a sub-optimum treatment plan was recommended in 8% of cases; and in 9% of cases the video-link management plans were judged to be inappropriate. In 20% of cases the dermatologist was unable to recommend a suitable management plan by video-link. There were significant differences in the ability to recommend an optimum management plan by video-link when a different dermatologist made the reference management plan. The results indicate that a high proportion of dermatological conditions can be successfully managed by realtime teledermatology.

Preliminary results from the Northern Ireland arms of the UK Multicentre Teledermatology Trial:is clinical management by realtime teledermatology possible?

Results from phase 1 of the UK Multicentre Teledermatology Trial demonstrated the diagnostic accuracy of realtime teledermatology using low-cost equipment. Phase 2 of the trial aimed to assess its effectiveness as a management tool for dermatological disease. Teledermatology consultations were organized between two health centres and two hospitals in Northern Ireland using low-cost videoconferencing equipment. For 205 patients seen by a dermatologist over the video-link a diagnosis and management plan were recorded. A subsequent face-to-face consultation was arranged on the same day to confirm the diagnosis and treatment regime. A comparison of these management plans revealed that the same plan was recommended in 64% of cases; the teledermatologist was unable to advocate a suitable management plan in 19% of cases; a suboptimal treatment plan was suggested by the teledermatologist in 6% of cases; and in 11% of cases, the teledermatologist suggested an inappropriate treatment plan. These findings indicate that appropriate clinical management was possible in approximately two-thirds of dermatology consultations via the video-link.

Burkholderia multivorans survival and trafficking within macrophages

Cystic fibrosis (CF) patients are at great risk of opportunistic lung infection, particularly by members of the Burkholderia cepacia complex (Bcc). This group of bacteria can cause damage to the lung tissue of infected patients and are very difficult to eradicate due to their high levels of antibiotic resistance. Though the highly virulent B. cenocepacia has been the focus of virulence research for the past decade, B. multivorans is emerging as the most prevalent Bcc species infecting CF patients in North America. Despite several studies detailing the intramacrophage trafficking and survival of B. cenocepacia, no such data exists for B. multivorans. Our results demonstrated that clinical CF isolates, C5568 and C0514, and an environmental B. multivorans isolate, ATCC17616, were able to replicate and survive within murine macrophages in a manner similar to B. cenocepacia K56-2. These strains were also able to survive but were unable to replicate within human THP-1 macrophages. Differences in macrophage uptake were observed among all three B. multivorans strains; these variances were attributed to major differences in O-antigen production. Unlike B. cenocepacia-containing vacuoles, which delay phagosomal maturation in murine macrophages by 6 h, all B. multivorans containing vacuoles co-localized with late endosome/lysosomal marker LAMP-1 and the lysosomal marker dextran within 2 h of uptake. Together, these results indicate that while both Bcc species are able to survive and replicate within macrophages, they utilize different intramacrophage survival strategies. To observe differences in virulence the strains were compared using the Galleria mellonella model. When compared to the B. multivorans strains tested, B. cenocepacia K56-2 is highly virulent in this model and killed all worms within 24 h when injected at 107 CFU. B. multivorans clinical isolates C5568 and C0514 were significantly more virulent than the soil isolate ATCC17616, which was avirulent, even when worms were injected with 107 CFU. These results suggest strain differences in the virulence of B. multivorans isolates.

Equal Security: Europe and the Strategic Arms Limitation Talks, 1968-1976

SALT threatened to institutionalize a bipolar world order. NWS and NNWS alike feared that the US and SU will prioritize global security principles such as systemic stability and conflict stability to Atlantic and European security. Endangered was Europe’s security and position in the future world order. Parity in strategic weapons invalidated the US nuclear umbrella. An ABM deployment and a non-transfer regime threatened Europe’s nuclear defence options. The danger of a Limited War or a denuclearization of Central Europe led to a European co-ordination on nuclear arms control to assure the preservation of the West and the future of Europe.

Receptor-mediated endocytosis and intracellular trafficking of insulin and low-density lipoprotein by retinal vascular endothelial cells

PURPOSE: The authors investigated the receptor-mediated endocytosis (RME) and intracellular trafficking of insulin and low-density lipoprotein (LDL) in cultured retinal vascular endothelial cells (RVECs). METHODS: Low-density lipoprotein and insulin were conjugated to 10 nm colloidal gold, and these ligands were added to cultured bovine RVECs for 20 minutes at 4 degrees C. The cultures were then warmed to 37 degrees C and fixed after incubation times between 30 seconds and 1 hour. Control cells were incubated with unconjugated gold colloid at times and concentrations similar to those of the ligands. Additional control cells were exposed to several concentrations of anti-insulin receptor antibody or a saturating solution of unconjugated insulin before incubation with gold insulin. RESULTS: Using transmission electron microscopy, insulin gold and LDL gold were both observed at various stages of RME. Insulin-gold particles were first seen to bind to the apical plasma membrane (PM) before clustering in clathrin-coated pits and internalization in coated vesicles. Gold was later visualized in uncoated cytoplasmic vesicles, corresponding to early endosomes and multivesicular bodies (MVBs) or late endosomes. In several instances, localized regions of the limiting membrane of the MVBs appeared coated, a feature of endosomal membranes not previously described. After RME at the apical PM and passage through the endosomal system, the greater part of both insulin- and LDL-gold conjugates was seen to accumulate in large lysosome-like compartments. However, a small but significant proportion of the internalized ligands was transcytosed and released as discrete membrane-associated quanta at the basal cell surface. The uptake of LDL gold was greatly increased in highly vacuolated, late-passage RVECs. In controls, anti-insulin receptor antibody and excess unconjugated insulin caused up to 89% inhibition in gold-insulin binding and internalization. CONCLUSION: These results illustrate the internalization and intracellular trafficking by RVECs of insulin and LDL through highly efficient RME, and they provide evidence for at least two possible fates for the endocytosed ligands. This study outlines a route by which vital macromolecules may cross the inner blood-retinal barrier.