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Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: a study using photonic force microscopy.

It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 microm in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles.

Actins↗

Cryptographic protection of health information: cost and benefit.

Medical, legal, and economic reasons inevitably force health care establishments to apply more and more open distributed IT systems rather than the less flexible and more expensive mainframes. Managing, for example, electronic patient records by various users at different locations by means of large scale client server systems requires new security provisions for storing, archiving and communicating those data. Using an analogy, data processing is being changed from railroads to highways. Formerly, only one engine-driver was responsible for the security of a whole train whereas now the car-drivers themselves are responsible each for his own car. Unless the cars are equipped with suitable security mechanisms like breaks and safety belts this change endangers individuals within and outside the cars. Cryptography provides many of the relevant security mechanisms for open distributed health care IT systems. Indeed, suitable cost effective cryptographic products are available but are rarely found in health care IT systems. The reason is more political than economic, diverging national security interests in the EU have prevented strong security in public telecommunication infrastructures arguing that, e.g. criminals would profit, too. The resulting uncertainty of investments delays the development, standardisation and installation of cryptographic solutions.

Computer Security↗

Population monitoring: experience with residents exposed to uranium mining/milling waste.

More emphasis should be placed upon using biomarkers to address potential health risk among populations exposed to high concentrations of environmental toxicants. Among these studies, those which integrate exposure measurements with analyses of validated biomarkers may provide more reliable information for risk assessment and disease prevention. We have used a multidisciplinary approach to elucidate potential health hazards in a population living around uranium mining/milling facilities. The study included 24 target and 24 control residents who were matched for age and gender and selected based on time of residence in the study areas and proximity to mining/milling sites. Environmental samples were analyzed for uranium-238 (238U) concentrations and lead isotope ratios using inductively coupled plasma-mass spectrometry (ICP-MS) procedures, and blood samples were collected for cytogenetic analysis. We found that the 238U concentrations in soil samples were significantly higher than those in the control areas. In addition, the concentrations in the surface soil were significantly higher than in the subsurface soil (p<0.05) from target areas indicating environmental contamination by the mining/milling activities. Lead isotope data from soil samples taken near a railroad transfer location was significantly different from those of other sites, indicating contamination by non-native ore transported from sources outside of the region to local milling facilities for processing. Therefore, local residents have been exposed to low levels of radioactive contamination from the mining/milling activities on a daily basis for many years. From our cytogenetic analysis, the target population had more chromosome aberrations than the controls, although the differences were not significant (p<0.05). However, using our challenge assay, cells from the target population had a significantly abnormal DNA repair response, compared to cells from the same control population. In conclusion, the observed environmental contamination by uranium is consistent with the observed genotoxic effects in the target residents. Therefore, the residents have increased health risk and some of the health problems will most likely be related to exposure to the radioactive contaminants. Since the chromosome aberration frequency revealed increased, but not significant differences between the exposed and the control populations, we conclude that the health risk among the exposed residents is similar to those among nuclear workers.

Anencephaly↗

Guided wave dispersion curves for a bar with an arbitrary cross-section, a rod and rail example.

Theoretical and experimental issues of acquiring dispersion curves for bars of arbitrary cross-section are discussed. Since a guided wave can propagate over long distances in a structure, guided waves have great potential for being applied to the rapid non-destructive evaluation of large structures such as rails in the railroad industry. Such fundamental data as phase velocity, group velocity, and wave structure for each guided wave mode is presented for structures with complicated cross-sectional geometries as rail. Phase velocity and group velocity dispersion curves are obtained for bars with an arbitrary cross-section using a semi-analytical finite element method. Since a large number of propagating modes with close phase velocities exist, dispersion curves consisting of only dominant modes are obtained by calculating the displacement at a received point for each mode. These theoretical dispersion curves agree in characteristic parts with the experimental dispersion curves obtained by a two-dimensional Fourier transform technique.

Journal Article↗

Behavior of PAHs during cold storage of historically contaminated soil samples.

The stability of historically polycyclic aromatic hydrocarbon (PAH)-contaminated soils during cold storage was investigated. Samples from two former manufactured gas plants exhibited quantitative recoveries of PAHs over the whole period of sample holding at 4 degrees C in the dark (8-10 months), whereas significant losses of PAHs were observed for soils received from a former railroad sleeper preservation plant with low molecular weight compounds being notably more affected compared to heavier PAHs. Already after 2 weeks of holding time, 3-ring PAHs in one of theses samples were down to 29-73% of the initial concentration and significant losses were observed for up to 5-ring compounds. Dissipation of PAHs was found to be predominantly due to aerobic microbial metabolism since sodium azide poisoned samples showed quantitative recoveries for all PAHs over the entire storage time of 3 months. A similar stabilizing effect was observed for freezing at -20 degrees C as means of preservation. Except for acenaphthene, no significant loss for any of the PAHs was observed over 6 weeks of holding time. Eventually, selected chemical, physical, and biological parameters of two soils were investigated and identified as potential indicators for the stability of PAH-contaminated soil samples.

Biodegradation, Environmental↗

Coronary heart disease in middle-aged Frenchmen. Comparisons between Paris Prospective Study, Seven Countries Study, and Pooling Project.

A systematic comparison was made of the incidence rates of major coronary heart disease (CHD), defined as fatal and non-fatal myocardial infarction and probable CHD deaths, observed in the Paris Prospective Study, the European and American cohorts of the Seven Countries Study, and the populations of the Pooling Project. The Paris study results were adjusted to the age-distribution and follow-up duration of the other studies. The major CHD incidence rate in the Paris study proved to be intermediate between those observed in Northern and Southern European populations and half to one-third those observed in the American populations. Mean risk-factor levels were of the same order of magnitude as in the whole European group and were lower than in the Pooling Project population, particularly for cholesterol and smoking. The coefficients of risk factors in the multivariate analysis of risk among the four studies showed similar gradients of risk except for a steeper gradient with smoking in the Paris Prospective Study. After adjustment to the risk-factor levels, major CHD incidence in the Paris study was comparable with that in the European population but lower than those in the U.S. Railroad population (ratio of predicted numbers of cases=1.56) and the pooling project population (ratio of predicted numbers of cases=2.24).

Adult↗

[Management endourologic of pyeloureteral junction stenosis].

OBJECTIVES: To report our experience with endourologic methods in the treatment of pyeloureteral stenosis in children. MATERIALS AND METHODS: From July 2004, 7 patients from 9 months to 15 years old with pyeloureteral junction stenosis (PUJ) diagnosis underwent endourologic repair. An endourological dilatation was made under radioscopic control. The procedures consist of an initial cystoscopy with a retrograde placement of catheter (4 or 5 Fr) and the guide wire (0,014''-or 0,035''). The high pressure balloon (3 to 5 Fr) was then railroad over the wire and positioned across the stenosis for dilatation. A double J stent (3 to 6 Fr) was then introduced, remaining it during 6 weeks. RESULTS: There was no intraoperative complications. Median inhospital stay was 2 days (range, 2 to 8). The double J stent was removed without complications. All patients are asymptomatic with improvement in excretion times (MAG3 renography) and antero-posterior renal pelvis diameter (ultrasound measurement). CONCLUSIONS: Balloon dilatation is a viable option in the management of PUJ obstruction even in children under one year old, with minimal morbidity.

Adolescent↗

New methods of dealing with the complications of panendoscopy.

A 70-year-old man with chronic obstructive airways disease was scheduled to undergo panendoscopy following a course of radiotherapy for carcinoma of the larynx. He was anaesthetized using a propofol infusion and high frequency jet ventilation (HFJV). The jet ventilation catheter was left in situ at the end of the procedure. This enabled oxygenation to be maintained in the presence of post-operative laryngospasm by re-attaching the jet ventilator. Subsequently he developed respiratory failure, and a Bullard laryngoscope was used to visualize the vocal folds despite oedema of the tumour which made direct laryngoscopy impossible. A catheter was passed through the biopsy channel of the Bullard, enabling HFJV to be commenced. A conventional endotracheal tube was then railroaded over the catheter to facilitate conventional ventilation.

Aged↗

Hydrothermal synthesis, structures, and magnetic properties of three novel 5-aminoisophthalic acid ligand bridged transition metal cation polymers.

Three novel 5-aminoisophthalic acid (AIP) bridged polymers [Co(C(8)NH(5)O(4))(H(2)O)](n)() (1), [Ni(C(8)NH(5)O(4))(H(2)O)(2)](n)() (2), and [Zn(C(8)NH(5)O(4))(H(2)O)](n)() (3) were synthesized by hydrothermal reactions and characterized by IR, Raman, elemental analysis, ESR, and magnetic measurements. X-ray single-crystal analyses were carried out for [Co(C(8)NH(5)O(4))(H(2)O)](n)() (1), which crystallizes in the triclinic system, space group P1 macro, with a = 6.477(1) A, b = 7.130(1) A, c = 9.826(2) A, alpha = 108.9(1) degrees, beta = 93.97(3) degrees, gamma = 98.82(3) degrees, and Z = 2; for [Ni(C(8)NH(5)O(4))(H(2)O)(2)](n)() (2), in the triclinic system, space group P1 macro, a = 6.425(1) A, b = 8.115(2) A, c = 10.146(2) A, alpha = 113.09(3)(o), beta = 99.64(3)(o), gamma = 98.90(3)(o), and Z = 2; and for [Zn(C(8)NH(5)O(4))(H(2)O)](n)() (3), in the monoclinic system, space group P2(1)/n, a = 9.044(1) A, b = 8.264(1) A, c = 11.646(1) A, beta = 100.77(1) degrees, and Z = 4. The single X-ray diffraction studies reveal that 1 consists of an infinite honeycomb layer formed by four crystallographically independent motifs packed alternatively together; 2 consists of an infinite neutral railroad-like linear polymer, and 3 consists of infinite layers of alternating four-coordinated Zn(II) cations and AIP ligands. Finally, they are all packed into beautiful three-dimensional frameworks through complicated hydrogen bonding. Antiferromagnetic and ferromagnetic behaviors were observed for 1 and 2 from the magnetic measurements.

Journal Article↗

Neuroblastoma and parental occupation.

OBJECTIVES: We evaluated parental occupation and the risk of neuroblastoma using data from a large case-control study conducted by the Children's Cancer Group and the Pediatric Oncology Group. METHODS: We compared the distribution of 73 paternal and 57 maternal occupational groups among 504 newly diagnosed cases of neuroblastoma and individually matched controls obtained by telephone random digit dialing in the United States and Canada. RESULTS: An increased risk of neuroblastoma was found for fathers employed as broadcast, telephone and dispatch operators (odds ratio [OR] = 6.1; 95% confidence interval [CI] = 0.7-50.9), electrical power installers and power plant operators (OR = 2.7; CI = 0.9-8.1), landscapers and groundskeepers (OR = 2.3; CI = 1.0-5.2), and painters (OR = 2.1; CI = 0.9-4.8). Elevated odds ratios were found for mothers employed as farmers and farm workers (OR = 2.2; CI = 0.6-8.8), florists and garden store workers (OR = 2.4; CI = 0.6-9.9), hairdressers and barbers (OR = 2.8; CI = 1.2-6.3), electric power installers and power plant operators, and sailors, fishers, and railroad workers. No increase in risk was found for other paternal occupations previously associated, including electricians, electrical equipment assemblers and repairers (OR = 1.1; CI = 0.6-2.0), or welders (OR = 0.5; CI = 0.1-1.6). CONCLUSION: The study reinforced some prior evidence of increased risks in electrical, farming and gardening, and painting occupations, but failed to confirm other previously reported associations. Further analyses of exposure to electromagnetic fields, metals, solvents, and pesticides are currently under way.

Adolescent↗

Ease of laryngeal passage during fibreoptic intubation: a comparison of three endotracheal tubes.

BACKGROUND: The use of a fibreoptic bronchoscope to facilitate endotracheal intubation is well established in modern anaesthetic practice. Difficulty may be encountered when inserting an endotracheal tube over the fibrescope as the bevelled tip can impinge on the vocal cords or epiglottis and impede advancement through the laryngeal inlet. Intavent have recently developed a tapered tip tube for use with their Intubating Laryngeal Mask Airway. A randomised, double-blind study was performed to compare the ease of railroading three different tubes over a fibrescope placed in the trachea. METHODS: We studied 54 patients presenting for elective dental surgery. General anaesthesia was induced with propofol 2-3 mg/kg, fentanyl 1-1.5 microg/kg, and atracurium 0.5 mg/kg and maintained with oxygen (5 l/min) and isoflurane 1-2%. Nasotracheal fibreoptic intubation was attempted in all patients. In each case the ease of tube advancement over the fibrescope and into the trachea was evaluated by the blinded observer, using the classification system (Grade 0-2) described by Jones et al. RESULTS/CONCLUSION: The Intavent tube was found to be superior for nasotracheal fibreoptic intubation to either the Mallinckrodt reinforced tube (P<0.034) or the Portex Blue Line tube (P<0.004).

Adolescent↗

Use of GFP tags to monitor localization of different luciferases in E. coli.

The utility of the green fluorescent protein (GFP) as a probe to monitor protein localization in living cells is gaining a great deal of attention. In this study, to understand the localization of luciferases in E. coli, we have attached GFP tags at both the N- and the C-terminus of firefly luciferase (FF-Luc)(from Pyrocoelia miyako) and of red (RE-Luc) and green (GR-Luc) bioluminescence-emitting luciferases (from Phrixothrix railroad-worms), respectively. There was no significant change in the bioluminescence emission spectrum for any of the three luciferases following the tagging with GFP at either the N- or C-terminus, confirming the absence of energy transfer between one another. Using confocal imaging microscopy, we observed that all three luciferases expressed in the E.coli cultured at 37 degrees C tend to aggregate and are seen to localize in the poles, thus confirming their poor folding properties. In contrast, in the E.coli cultured at 18 degrees C FF-Luc was found to be highly expressed in the soluble form when compared to RE-Luc and GR-Luc. These results support our previous finding that the folding properties of FF-Luc and RE/GR-Luc are totally different.

Cytosol↗

Crystal engineering of coordination polymers using 4,4'-bipyridine as a bond between transition metal atoms.

Coordination polymers have attracted an enormous interest among chemists due to their novel physical and chemical properties. This review describes the role of 4,4'-bipyridine in discovering various coordination polymers with novel topologies that range from one-dimensional to three dimensional. The geometries of coordination polymers of bipy include linear, zigzag, four-fold helices, molecular antenna, ladder, railroad, double, triple and quadruple chains, bilayer, square and rectangular grid, honeycomb layers, Lincoln Logs, 3D frames, diamondoid, 4(2) x 8(2) and cubic networks.

Journal Article↗

Noise exposure associated with hearing aid use in industry.

Although noise may be innocuous in many vocational environments, there is a growing concern in industry that it can reach hazardous levels when amplified by hearing aids. This study examined the daily noise exposures associated with hearing aid use in industry. This was done by both laboratory and site measurements in which hearing aids were coupled to the microphone of an integrating sound level meter or dosimeter. The former method involved the use of recorded railroad and manufacturing noise and a Bruel and Kjaer 4128 Head and Torso simulator. In the latter procedure, a worker wore one of three hearing aids coupled to a dosimeter during 8-hour shifts in a manufacturing plant. Both methods demonstrated that even when amplified by mild-gain hearing aids, noise exposures rose from time-weighted averages near 80 dBA to well above the OSHA maximum of 90 dBA. The OSHA maximum was also exceeded when moderate and high gain instruments were worn in non-occupational listening environments. The results suggest that current OSHA regulations that limit noise exposure in sound field are inappropriate for hearing aid users.

Hearing Aids↗

Orotracheal fibreoptic intubation for rapid sequence induction of anaesthesia.

We assessed whether flexible fibreoptic-guided orotracheal intubation could be rapidly and successfully achieved during a simulated rapid sequence induction in 30 anaesthetised and paralysed patients. Rapid sequence induction was simulated by applying practised cricoid pressure. Using a flexible fibreoptic laryngoscope with camera and closed circuit television, an anaesthetist experienced with the technique performed orotracheal endoscopy and intubation with a cuffed 7.0-mm Portex tracheal tube through a VBM Bronchoscope Airway. Fibreoptic intubation was successful at the first attempt in 28 patients (93%); two patients required two attempts. Mean (SD) time from removal of the facemask from the patient's face to the appearance of carbon dioxide in the expired breath after intubation was 111 (46) s (median 100 s; range 54-195 s). There were one or more difficulties in 13 patients (43%). These difficulties were largely avoidable and included problems with fibreoptic equipment, the Bronchoscope Airway, copious secretions, cricoid pressure or railroading of the tracheal tube. Flexible fibreoptic-guided orotracheal intubation may have a place in the management of failed intubation during a rapid sequence induction.

Adolescent↗

Use of the flexible intubating fibrescope for tracheal re-intubation in a patient with difficult extubation.

Difficulty in tracheal extubation was experienced in a patient following major maxillofacial surgery for reconstruction of the maxilla using bone grafts and a microvascular free flap. With the aid of an intubating flexible fibrescope, the cause of the difficulty was identified as a stitch accidentally transfixed through the tracheal tube. Tracheal re-intubation was required to facilitate surgical exploration to remove the stitch and the proximal end of the tube. The tip of an Olympus LF-2 intubating fibrescope was successfully negotiated in the trachea alongside the original tube with its cuff deflated. This allowed safe and speedy railroading of a new tube immediately after the distal end of the original tube was removed.

Adult↗

Random amplified polymorphic DNA variation among remnant big bluestem (Andropogon gerardii vitman) populations from Arkansas' grand prairie

Random amplified polymorphic DNA (RAPD) analysis was used to characterize genetic diversity and genetic distinctiveness of Andropogon gerardii from remnant Arkansas prairies. Six oligonucleotide primers, which generated 37 RAPD bands, were used to analyse 30-32 plants from six Grand Prairie populations, Baker Prairie (Arkansas Ozarks), two Illinois prairies and two cultivars. Genetic diversity of the Arkansas remnants ranged from 82.7 to 99.3%, with 89% of the total genetic variation within and 11% among populations. The partitioning of genetic variation was consistent with that reported for other outcrossing perennial grasses, using the more conservative allozyme markers. Principal component analysis indicated a northern and southern association within Arkansas' Grand Prairie. Although there was no genetic structuring at the landscape level, the Illinois prairies and cultivars were different from all Arkansas prairies tested. There was significant within-population structuring in four of the seven Arkansas remnants, with a negative relationship between genetic similarity and geographical distance. The three nonstructured populations were from a linear railroad remnant, suggesting different population-level dynamics from nonlinear prairies. The results of this study indicated that small isolated remnant big bluestem populations were not genetically depauperate and that genetic relationships among populations could not be predicted solely on geographical proximity.

Journal Article↗

The influence of insertion of a critical residue (Arg356) in structure and bioluminescence spectra of firefly luciferase.

The firefly bioluminescence reaction, which uses luciferin, Mg-ATP, and molecular oxygen to yield an electronically excited oxyluciferin, is carried out by luciferase and visible light is emitted. The bioluminescence color of firefly luciferases is determined by the luciferase structure and assay conditions. Among different beetle luciferases, those from Phrixothrix railroad worm emit either yellow or red bioluminescence colors. Sequence alignment analysis shows that the red-emitter luciferase from Phrixothrix hirtus has an additional Arg residue at 353, which is absent in firefly luciferases. We report here the construction and purification of a mutant at residue Arg(356), which is not conserved in beetle luciferases. By insertion of an additional residue (Arg(356)) using site-specific insertion mutagenesis in a green-emitter luciferase (Lampyris turkestanicus) the color of emitted light was changed to red and the optimum temperature of activity was also increased. Insertion of this Arg in an important flexible loop showed changes of the bioluminescence color and the luciferase reaction took place with relatively retention of its basic kinetic properties such as Km and relative activity. Comparison of native and mutant luciferases using homology modeling reveals a significant conformational change of the flexible loop in the red mutant. Movement of flexible loop brought about a new ionic interaction concomitant with a change in polarity of the emitter site, thereby leading to red emission. It is worthwhile to note that the increased optimum temperature and emission of red light might make mutant luciferase a suitable reporter for the study of gene expression and bioluminescence imaging.

Amino Acid Sequence↗