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The future of human spaceflight.

After the Apollo Moon program, the international space station represents a further milestone of humankind in space, International follow-on programs like a manned return to the Moon and a first manned Mars Mission can be considered as the next logical step. More and more attention is also paid to the topic of future space tourism in Earth orbit, which is currently under investigation in the USA, Japan and Europe due to its multibillion dollar market potential and high acceptance in society. The wide variety of experience, gained within the space station program, should be used in order to achieve time and cost savings for future manned programs. Different strategies and roadmaps are investigated for space tourism and human missions to the Moon and Mars, based on a comprehensive systems analysis approach. By using DLR's software tool FAST (Fast Assessment of Space Technologies), different scenarios will be defined, optimised and finally evaluated with respect to mission architecture, required technologies, total costs and program duration. This includes trajectory analysis, spacecraft design on subsystem level, operations and life cycle cost analysis. For space tourism, an expected evolutionary roadmap will be described which is initiated by short suborbital tourism and ends with visionary designs like the Space Hotel Berlin and the Space Hotel Europe concept. Furthermore the potential space tourism market, its economic meaning as well as the expected range of the costs of a space ticket (e.g. $50,000 for a suborbital flight) will be analysed and quantified. For human missions to the Moon and Mars, an international 20 year program for the first decades of the next millennium is proposed, which requires about $2.5 Billion per year for a manned return to the Moon program and about $2.6 Billion per year for the first 3 manned Mars missions. This is about the annual budget, which is currently spend by the USA only for the operations of its Space Shuttle fleet which generally proofs the affordability of such ambitious programs after the build-up of the International Space Station, when corresponding budget might become again available.

Equipment Design↗

Background monitoring and long-range transport of atmospheric CFC-11 and CFC-12 at Kosan, Korea.

The background concentrations of atmospheric CFC-11 and CFC-12 were monitored to assess their impact on stratospheric ozone depletion and global warming from September 1995 to March 1999 at Kosan, Korea, located at eastern margin of the Asian Continent. The concentrations of atmospheric CFC-11 at Kosan have decreased slightly, at a rate of -2.5 pptv yr(-1), over the period in response to the Montreal Protocol. The CFC-12 mixing ratio at Kosan continues to increase in the atmosphere at a rate of 5.7 pptv yr(-1) despite international regulations, because of its extreme atmosphere persistence. Recent trends of these two chlorofluorocarbons at Kosan, Korea were concordant with those of the northern hemispheric background monitored unit at Mauna Loa, Hawaii. The maximum seasonal mean mixing ratios of CFC-11 and CFC-12 at Kosan, Korea, were 270 +/- 4 pptv in the spring and 538 +/- 9 pptv in the winter, and the corresponding seasonal minima were 267 +/- 7 and 529 +/- 12 pptv. This occurred in the summer and was due to southeasterly winds from the northwestern Pacific Ocean. By performing a three-day isentropic backward trajectory analysis, it was shown that air masses at Kosan, and with the exception of summer, mainly originated from central and northern China. In particular, the mixing ratios of these two contaminant species are closely related with their air mass trajectories.

Air Movements↗

Fabrication, characterization and evaluation of bioceramic hollow microspheres used as microcarriers for 3-D bone tissue formation in rotating bioreactors.

Novel bioactive ceramic hollow microspheres with an apparent density in the range 0.8-1.0 g cm(-3) have been developed as microcarriers for 3-D bone tissue formation in rotating-wall vessels (RWV). Hollow ceramic microspheres with a composition of 58-72% SiO2, 28-42% Al2O3 (wt%) and an apparent density 0.8-1.0 g cm(-3) were pretreated in 1.0 N NaOH for 2 h before being coated with synthesized calcium hydroxyapatite (HA) particulate sol. The HA-coated hollow microspheres were sintered for 1 h at 600, 800 and 1000 degrees C. SEM analysis revealed that the grain size and pore size of the calcium phosphate coating increased with the sintering temperature. FTIR analysis showed that crystalline calcium hydroxyapatite was present in the coatings sintered at 600 and 800 degrees C. When sintered at 1000 degrees C, the coating consisted of alpha-tricalcium phosphate. All the coatings adhered well, independent of sintering temperature. The trajectory analysis revealed that the hollow microsphere remained suspended in a rotating-wall vessel (RWV), and experienced a low shear stress (approximately 0.6 dyn cm(-2)). Cell culture studies using rat bone marrow stromal cells and osteosarcoma cells (ROS 17/2.8) showed that the cells attached to and formed 3-D aggregates with the hollow microspheres in a RWV. Extracellular matrix was observed in the aggregates. These data suggest that these hollow bioactive ceramic microspheres can be used as microcarriers for 3-D bone tissue formation in vitro, as well as for the study of the effects of microgravity on bone cell functions.

Animals↗

Ascites reprograms innate lymphoid immune cells in ovarian cancer by promoting ILC2 enrichment and dysfunctional NK-cell states.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is commonly accompanied by malignant ascites, a clinically relevant tumor niche that promotes immune evasion, metastasis, and treatment resistance. Although natural killer (NK)-cell dysfunction has been described in ovarian cancer, the broader innate lymphoid landscape of ascites and the mechanisms linking ascites-derived signals to innate immune suppression remain insufficiently resolved. METHODS: We performed single-cell RNA sequencing of NK/innate lymphoid cells from ovarian cancer ascites to define cellular heterogeneity and differentiation states. Functional assays assessed NK-cell cytotoxicity, degranulation, and receptor expression following exposure to patient-derived ascites, with or without transforming growth factor-β (TGF-β) receptor inhibition. Proteomic profiling was used to characterize the soluble ascites milieu, and clinical associations were examined for innate lymphoid subsets. RESULTS: Single-cell analysis identified eight transcriptionally distinct NK/innate lymphoid states, including cytotoxic, precursor, early-like, tolerant/immunoregulatory, regulatory, proinflammatory, and innate lymphoid populations. Ovarian cancer ascites was characterized by depletion of cytotoxic and precursor NK-cell states together with enrichment of early-like, tolerant, regulatory, pro-inflammatory, and innate lymphoid cell (ILC) populations. Trajectory analysis indicated impaired maturation toward terminally differentiated cytotoxic NK cells. Notably, ascites contained an expanded population of programmed cell death protein 1 (PD-1)+ ILC2s, which were more abundant in patients with shorter progression-free survival. In functional assays, short-term exposure of healthy donor NK cells to ascites suppressed degranulation and tumor-cell killing, reduced expression of activating receptors including NKp30 and DNAM-1, increased inhibitory receptor expression, and shifted NK cells toward a CD56highCD16low phenotype. Proteomic profiling supported a soluble milieu consistent with type 2 immune skewing and NK-cell suppression. Importantly, TGF-β receptor inhibition partially restored NK-cell activation and function in the presence of ascites. CONCLUSIONS: HGSOC ascites establishes a type 2-skewed immunoregulatory niche that coordinately drives NK cell dysfunction and PD-1+ ILC2 accumulation. The findings identify TGF-β-linked suppression and ascites-associated immune regulators as candidate immunotherapeutic vulnerabilities for restoring antitumor immunity in ovarian cancer.

Humans↗

Motor task difficulty and brain activity: investigation of goal-directed reciprocal aiming using positron emission tomography.

Differences in the kinematics and pattern of relative regional cerebral blood flow (rCBF) during goal-directed arm aiming were investigated with the use of a Fitts continuous aiming paradigm with three difficulty conditions (index of difficulty, ID) and two aiming types (transport vs. targeting) in six healthy right-handed young participants with the use of video-based movement trajectory analysis and positron emission tomography. Movement time and kinematic characteristics were analyzed together with the magnitude of cerebral blood flow to identify areas of brain activity proportionate to task and movement variables. Significant differences in rCBF between task conditions were determined by analysis of variance with planned comparisons of means with the use of group mean weighted linear contrasts. Data were first analyzed for the group. Then individual subject differences for the movement versus no movement and task difficulty comparisons were related to each individual subjects' anatomy by magnetic resonance imaging. Significant differences in rCBF during reciprocal aiming compared with no-movement conditions were found in a mosaic of well-known cortical and subcortical areas associated with the planning and execution of goal-directed movements. These included cortical areas in the left sensorimotor, dorsal premotor, and ventral premotor cortices, caudal supplementary motor area (SMA) proper, and parietal cortex, and subcortical areas in the left putamen, globus pallidus, red nucleus, thalamus, and anterior cerebellum. As aiming task difficulty (ID) increased, rCBF increased in areas associated with the planning of more complex movements requiring greater visuomotor processing. These included bilateral occipital, left inferior parietal, and left dorsal cingulate cortices--caudal SMA proper and right dorsal premotor area. These same areas showed significant increases or decreases, respectively, when contrast means were compared with the use of movement time or relative acceleration time, respectively, as the weighting factor. Analysis of individual subject differences revealed a correspondence between the spatial extent of rCBF changes as a function of task ID and the individuals' movement times. As task ID decreased, significant increases in rCBF were evident in the right anterior cerebellum, left middle occipital gyrus, and right ventral premotor area. Functionally, these areas are associated with aiming conditions in which the motor execution demands are high (i.e., coordination of rapid reversals) and precise trajectory planning is minimal. These same areas showed significant increases or decreases, respectively, when contrast means were compared with the use of movement time or relative acceleration time, respectively, as the weighting factor. A functional dissociation resulted from the weighted linear contrasts between larger (limb transport) or smaller (endpoint targeting) type amplitude/target width aiming conditions. Areas with significantly greater rCBF for targeting were the left motor cortex, left intraparietal sulcus, and left caudate. In contrast, those areas with greater rCBF associated with limb transport included bilateral occipital lingual gyri and the right anterior cerebellum. Various theoretical explanations for the speed/accuracy tradeoffs of rapid aiming movements have been proposed since the original information theory hypothesis of Fitts. This is the first report to relate the predictable variations in motor control under changing task constraints with the functional anatomy of these rapid goal-directed aiming movements. Differences in unimanual aiming task difficulty lead to dissociable activation of cortical-subcortical networks. Further, these data suggest that when more precise targeting is required, independent of task difficulty, a cortical-subcortical loop composed of the contralateral motor cortex, intraparietal sulcus, and caudate is activated. This is consistent with the role of motor cortex

Adult↗

Analysis of dynamics trajectories of DNA and DNA-drug complexes.

A FORTRAN-77 program is described which was applied for analysis of optimized structures and computer-generated dynamics trajectories of DNA and DNA-drug complexes. The CORDAN program (coordinates analysis) also can be used for various manipulations of DNA-drug complexes, i.e. inversion of asymmetric sites or rebuilding the structure of the intercalator, among others. These procedures can find application in drug design. Analysis of dynamics trajectory of neocarzinostatin antibiotic (NCS) intercalated to the A-DNA form of 5'GGATGGGAG:5'CTCCCATCC is presented. The procedures described can be used for detailed analysis of dynamics structures of DNA and their complexes with intercalating drugs.

Base Sequence↗

Molecular dynamics of sickle and normal hemoglobins.

Molecular dynamics (MD) simulations have been carried out for 62.5 ps on crystal structures of deoxy sickle cell hemoglobin (HbS) and normal deoxy hemoglobin (HbA) using the CHARMM MD algorithm, with a time step of 0.001 ps. In the trajectory analysis of the 12.5-62.5 (50 ps) simulation, oscillations of the radius of gyration and solvent-accessible surface area were calculated. HbS exhibited a general contraction during the simulation, while HbA exhibited a nearly constant size. The average deviations of simulated structures from the starting structures were found to be 1.8 A for HbA and 2.3 A for HbS. The average rms amplitudes of atomic motions (atomic flexibility) were about 0.7 A HbA and about 1.0 A for HbS. The amplitudes of backbone motion correlate well with temperature factors derived from x-ray crystallography. A comparison of flexibility between the alpha- and beta-chains in both HbA and HbS indicates that the beta-chains generally exhibited greater flexibility than the alpha-chains, and that the HbS beta-chains exhibit greater flexibility in the N-terminal and D- and F-helix regions than do those of HbA. The average amplitude of backbone torsional oscillations was about 9 degrees, a value comparable with that of other simulations, with enhanced torsional oscillation occurring primarily at the ends of helices or in loop regions between helices. Comparison of atomic flexibility and torsional oscillation results suggests that the increased beta-chain flexibility results from relatively concerted motions of secondary structure elements. The increased flexibility may play an important role in HbS polymerization.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗

The Effect of Slight Deformation on Thermocapillary-Driven Droplet Coalescence and Growth.

The collision efficiency of two slightly deformable drops in thermocapillary motion at small Reynolds and Marangoni numbers is determined by a trajectory analysis involving methodology from matched asymptotic expansions. The outer solution for two spherical drops which are nearly touching provides the contact force driving the inner solution. Accurate calculation of the contact force and near-contact motion is aided by new solutions for the mobility functions parallel and normal to the drops' line of centers that are valid at very small separations. Governed by a system of integro-differential equations coupling the flow inside the drops and that within the small gap, the inner solution allows demarcation of the regions of drop coalescence and separation. Apart from the driving force, the thin-film equations are unchanged to leading order from the buoyancy-driven case, since no additional singularity is introduced into the tangential stress by the presence of the finite temperature gradient. The interplay of small deformation, as measured by the capillary number (Ca), and attractive van der Waals forces controls the apparent contact motion. Results for the collision efficiency are mapped out for a range of five dimensionless parameters: Ca, size ratio, drop-to-medium viscosity ratio, drop-to-medium thermal conductivity ratio (&kcirc;), and a dimensionless Hamaker parameter. Since the only effect on the inner solution of an increase in the thermal conductivity ratio is an increase in the amount of time the drops spend in close approach, it is possible for the collision efficiency of two slightly deformable drops with higher &kcirc; to be greater than that for two similar drops with lower &kcirc;. This behavior differs from that of spherical drops, where an increase in thermal conductivity ratio always leads to a decrease in the collision efficiency, as a result of greater hydrodynamic interaction between the spherical drops due to the temperature gradient. In addition, collision efficiencies are provided for a model system of ethyl salicylate (ES) drops in diethylene glycol (DEG). The collision efficiency decreases rapidly with increasing drop size above a critical value, due to the increasing role of deformation in retarding the drainage of the thin film between two drops in close approach. Population dynamics simulations are performed for homogeneous suspensions of the ES/DEG system, showing that slight deformation limits droplet growth due to coalescence in dilute dispersions. Copyright 1999 Academic Press.

Journal Article↗

Experimental Investigation of the Orthokinetic Coalescence Efficiency of Droplets in Simple Shear Flow.

The coalescence efficiency of two droplets in simple shear flow was experimentally investigated. The effects of the radius of the colliding droplets, the viscosity of the continuous medium, and the radii ratio on the coalescence efficiency were studied. The coalescence efficiency was determined from the critical angle, alpha(crit), above which the droplets coalesce and below which no coalescence takes place. It was found that the coalescence efficiency decreases and then increases with the flow number. The theories of the drainage models and the trajectory analysis were unable to predict the experimental results. This was attributed to the inadequacy of the existing expression used for the critical film thickness. On the basis of the experimental data obtained a new expression for the critical film thickness was proposed. The new expression predicts a decrease followed by an increase in the critical film thickness. The increase in the critical film thickness is, perhaps, due to instabilities that take place at the interfaces. Implementing the proposed expression for the critical film thickness, the experimentally measured coalescence efficiency, the capture angle and the contact time were successfully predicted. The experimental investigation revealed that the coalescence efficiency does not depend on the radii ratio in the range 0.7 to 1. The experimental investigation also showed that the coalescence efficiency increases as the viscosity of the continuous phase decreases. Measuring the capture angle showed that coalescence can take place either in the compression or in the extensional quadrant of the shear plane. A variation in the capture angle and the contact time was observed for a given fixed set of conditions. The change of the angle alpha with time was measured. The measured values were compared to those calculated from an equation derived by R. S. Allan and S. G. Mason (J. Colloid Interface Sci. 17, pp. 383, 1962). A good agreement was obtained when the droplets were of equal radii and small in size. When the droplets were large in size and of different radii, the agreement was not satisfactory. Measuring the distance between the centers of the colliding droplets showed that the two droplets vibrated when they came close to each other. Copyright 2001 Academic Press.

Journal Article↗

Hemispheric control of the initial and corrective components of aiming movements.

This study examined whether the left and right hemispheres play differential roles in controlling the initial and corrective components of aiming movements. A simple aiming task was administered to 31 normal control subjects and 29 unilateral stroke patients (14 with right hemisphere damage and 15 with left hemisphere damage). Movement amplitude was varied (25, 64 and 100 mm) and reaction time, movement time and accuracy were measured. Through a trajectory analysis, initial and corrective movements were separated. The stroke patients performed the task with their ipsilateral arm which was compared to the normal controls' right or left are performance. Regardless of the movement amplitude the left hemisphere group's reaction time was slower, and the execution of the initial movement component was less accurate than controls. No performance deficits were found on corrective movements. Performance was not impaired for the right hemisphere group on any measures. These results are discussed in terms of the hemispheres' possible roles in controlling movements which are largely open or closed loop.

Aged↗

Complete nucleotide sequence of RNA segment 3 of bluetongue virus serotype 2 (Ona-A). Phylogenetic analyses reveal the probable origin and relationship with other orbiviruses.

The nucleotide sequence of the RNA segment 3 of bluetongue virus (BTV) serotype 2 (Ona-A) from North America was determined to be 2772 nucleotides containing a single large open reading frame of 2703 nucleotides (901 amino acid). The predicted VP3 protein exhibited general physiochemical properties (including hydropathy profiles) which were very similar to those previously deduced for other BTV VP3 proteins. Partial genome segment 3 sequences, obtained by polymerase chain reaction (PCR) sequencing, of BTV isolates from the Caribbean were compared to those from North America, South Africa, India, Indonesia, Malaysia and Australia, as well as other orbiviruses, to determine the phylogenetic relationships amongst them. Three major BTV topotypes (Gould, A.R. (1987) Virus Res. 7, 169-183) were observed which had nucleotide sequences that differed by approximately 20%. At the molecular level, geographic separation had resulted in significant divergence in the BTV genome segment 3 sequences, consistent with the evolution of distinct viral populations. The close phylogenetic relationship between the BTV serotype 2 (Ona-A strain) from Florida and the BTV serotypes 1, 6 and 12 from Jamaica and Honduras, indicated that the presence of BTV serotype 2 in North America was probably due to an exotic incursion from the Caribbean region as previously proposed by Sellers and Maaroof ((1989) Can. J. Vet. Res. 53, 100-102) based on trajectory analysis. Conversely, nucleotide sequence analysis of Caribbean BTV serotype 17 isolates suggested they arose from incursions which originated in the USA, possibly from a BTV population distinct from those circulating in Wyoming.

Amino Acid Sequence↗

Contact hypersensitivity promotes hair regeneration through SPP1-secreting macrophages.

Allergic contact dermatitis, or contact hypersensitivity (CHS), is a pathological adaptive immune response that paradoxically induces hair regeneration, yet its underlying mechanisms remain unclear. We integrated high-resolution spatial transcriptomics and single-cell RNA sequencing to map the intricate interactions between immune cells, stroma, and hair follicles during CHS-induced hair growth in mice. Among all immunocytes, macrophages underwent the most prominent compositional and functional remodeling. We resolved five transcriptionally distinct macrophage subsets, with contact hypersensitivity driving a shift from homeostatic antigen-presenting cells toward a pro-inflammatory CD14+SPP1+ population. Trajectory analysis revealed divergent differentiation paths under homeostatic versus allergic conditions, highlighting the plasticity of skin macrophages. Mechanistically, CD14+SPP1+ macrophages secreted SPP1 (osteopontin), which engaged CD44 on hair follicle stem cells to activate PI3K-AKT signaling and trigger their proliferation. Notably, canonical pro-inflammatory cytokine signaling through TNF-α and IL-1 was dispensable for this process, underscoring the specificity of the SPP1-CD44 axis in immune-mediated hair regeneration. These findings reveal a macrophage-dependent mechanism of immune-mediated hair regeneration, offering therapeutic insights into immune-stem cell crosstalk.

Journal Article↗

Weather factors in the prediction of western equine encephalitis epidemics in Manitoba.

Cases of western equine encephalitis in horses in 1987 in western USA and Manitoba, Canada were examined by backward trajectory analysis of winds. Culex tarsalis mosquitoes infected with western equine encephalitis virus could have been carried on southerly winds from Texas and Oklahoma to northern USA and from there to Manitoba. The presence of the Polar front over North Dakota and Minnesota at the end of July would have led to the landing of Cx. tarsalis in Montana and Wisconsin and prevented further carriage into Manitoba. Temperatures in southern Texas during the winter months (average daily maximum temperatures 19.7 degrees C and higher) would have permitted continuous transmission of western equine encephalitis virus by Cx. tarsalis in this area. Weather factors involved in outbreaks from 1975-88 were analysed to see if epidemics in Manitoba (23 or more cases in horses) could be predicted. The conditions for epidemics could be defined as follows: (a) the number of cases in horses in USA was 98 or more, (b) winds were southerly with speeds 45 kmh-1 or higher, and (c) counts of Cx. tarsalis females/light trap per day were 3.2 or higher. There were 3 or fewer cases in Manitoba, when the number of cases in USA was 27 or less, even when Cx. tarsalis counts were higher than 3.2. With Cx. tarsalis counts below 3 and/or unsuitable winds, or the Polar front further south, the number of cases in Manitoba was between 0 and 17, even when the number of cases in USA was from 38-172. Without information on the extent of infection further south, the weather variables would probably be more useful in excluding the possibility of an epidemic in Manitoba than in predicting one.

Animals↗

Molecular dynamics simulation of the antimicrobial salivary peptide histatin-5 in water and in trifluoroethanol: a microscopic description of the water destructuring effect.

The results of 520 ps molecular dynamics simulation of histatin-5, a small peptide present in human saliva and possessing antimicrobial activity, dissolved in water and in 2,2,2-trifluoroethanol, are reported. The simulations indicate that histatin-5 is destabilized in water and begins to unfold after 250 ps, while in organic solvent it maintains a regular secondary structure throughout the trajectory. Analysis of the peptide-solvent hydrogen bonds indicates that 2,2,2-trifluoroethanol is a poorer proton acceptor than water. The fluorine atom of the alcohol is almost never engaged in a hydrogen bond and the organic solvent interacts mainly with the peptide through its hydroxyl group. For some residues analysis of the solvent residence time indicated longer values for 2,2,2-trifluoroethanol than for water. The most striking difference is related to the number of times the solvent enters and leaves the first coordination shell of the peptide. This value was more than one order of magnitude higher for water than for the alcohol, suggesting that this may be the main cause of alpha-helix destabilization perpetrated by water.

Amino Acid Sequence↗

Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development.

Pancreatic endocrine-exocrine crosstalk plays a key role in normal physiology and disease and can be altered by host metabolic states, such as obesity. Classically, endocrine islet beta (β) cell secretion of insulin is thought to promote the development of obesity-associated pancreatic adenocarcinoma (PDAC), an exocrine cell-derived tumor. Here, we show that β cell expression of the peptide hormone cholecystokinin (CCK) is necessary and sufficient for obesity-associated PDAC progression in mice and that CCK expression - rather than insulin - correlates strongly with enhanced tumorigenesis. Single-cell RNA-sequencing, in silico latent-space archetypal and trajectory analysis, and experimental lineage tracing in vivo reveal that obesity induces the expansion of postnatal immature β cells, which adapt to express CCK via stress-responsive JNK/cJun signaling. Finally, obesity perturbs CCK-dependent peri-islet exocrine cell transcriptional states and enhances islet-proximal tumor formation. These results define endocrine-exocrine CCK signaling as a bona fide driver of obesity-associated PDAC development and uncover avenues to target the endocrine pancreas to subvert exocrine tumorigenesis.

Animals↗

Cell-body curvature reduces stall frequency to enhance Vibrio cholerae swimming and chemotaxis through hydrogels.

The swimming motility of the bacterial pathogen Vibrio cholerae is a virulence factor that aids in breaching the mucus layer. V. cholerae has a curved cell shape, and previous work demonstrated that loss of curvature decreases infectivity. Here, we investigate the mechanism by which curvature affects single-cell motility. We compared the chemotactic performance of wild-type curved cells and straight mutants. The two exhibit similar swimming properties in liquid and viscous solutions but differ significantly in mucus-mimicking hydrogels, where curved cells demonstrate an 86% increase in chemotactic drift. Trajectory analysis indicates comparable swimming speeds, but straight mutants experience more frequent stalls, reducing total swimming time. Stalls further reduce chemotactic performance by imposing an average reorientation down the chemical gradient, regardless of cell shape. Coarse-grained molecular dynamics simulations corroborate these results across intestinal mucus hydrogel stiffnesses and identify an optimal curvature for movement through hydrogel-like meshes, close to the pathogen's median curvature. These findings highlight cell shape's role in pathogenicity and the need to study bacterial behaviors under conditions more closely mimicking the host environment.

Vibrio cholerae↗

Indoor-outdoor levels of nitrogen and sulphur species and their relation to air flow in Antigonish, Nova Scotia.

A study was conducted in Antigonish, Nova Scotia, to determine the extent to which acid rain related pollutants are present in indoor ambient air. The pollutant study included: fine (0 to 2.5 micron) and coarse (2.5 to 10 micron) particulates, sulphates, nitrates, acidity (H2SO4 and HNO3), SO2 and NO2. During the 3 1/2 month study, maximum levels of 173n equivalent/m3 fine sulphate and 55 n equivalent/m3 H2SO4 were recorded for outdoor air within the town site compared to corresponding values of 110 n equivalent/m3 and 13 n equivalent/m3 for indoor air. Based on back trajectory analysis, wind direction, and sulphuric acid content, it was postulated that local or medium range pollution sources are predominant in the winter while long range transport originating from the United States produces the major episodes when SW winds are persistent.

Air Movements↗

Structure of the Sm binding site from human U4 snRNA derived from a 3 ns PME molecular dynamics simulation.

A molecular dynamics simulation of the Sm binding site from human U4 snRNA was undertaken to determine the conformational flexibility of this region and to identify RNA conformations that were important for binding of the Sm proteins. The RNA was fully-solvated (>9,000 water molecules) and charge neutralized by inclusion of potassium ions. A three nanosecond MD simulation was conducted using AMBER with long-range electrostatic forces considered using the particle mesh Ewald summation method. The initial model of the Sm binding site region had the central and 3' stem-loops that flanked the Sm site co-axial with one another, and with the single-stranded Sm binding site region ([I] conformation). During the course of the trajectory, the axes of the 3' stem-loop, and later the central stem-loop, became roughly orthogonal from their original anti-parallel orientation. As these conformational changes occurred, the snRNA adopted first an [L] conformation, and finally a [U] conformation. The [U] conformation was more stable than either the [I] or [L] conformations, and persisted for the final 1 ns of the trajectory. Analysis of the structure resulting from the MD simulations revealed the bulged nucleotide, U114, and the mismatched Ag91-G110 base pair provided distinctive structural features that may enhance Sm protein binding. Based on the results of the MD simulation and the available experimental data, we proposed a mechanism for the binding of the Sm protein sub-complexes to the snRNA. In this model, the D1/D2 and E/F/G Sm protein sub-complexes first bind the snRNA in the [U] conformation, followed by conformational re-arrangement to the [I] conformation and binding of the D3/B Sm protein sub-complex.

Base Sequence↗