bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature dependence of the hydrophobic hydration and interaction of simple solutes: An examination of five popular water models
Authors: Paschek Dietmar
Published: March 2004

We examine five different popular rigid water models (SPC, SPCE, TIP3P, TIP4P, and TIP5P) using molecular dynamics simulations in order to investigate the hydrophobic hydration and interaction of apolar Lennard-Jones solutes as a function of temperature in the range between 275 and 375 K along the 0.1 MPa isobar. For all investigated models and state points we calculate the excess chemical potential for the noble gases and methane employing the Widom particle insertion technique. All water models exhibit too small hydration entropies, but show a clear hierarchy. TIP3P shows poorest agreement with experiment, whereas TIP5P is closest to the experimental data at lower temperatures and SPCE is closest at higher temperatures. As a first approximation, this behavior can be rationalized as a temperature shift with respect to the solvation behavior found in real water. A rescaling procedure inspired by the information theory model of Hummer et al. [Chem. Phys. 258, 349 (2000)] suggests that the different solubility curves for the different models and real water can be largely explained on the basis of the different density curves at constant pressure. In addition, the models that give a good representation of the water structure at ambient conditions (TIP5P, SPCE, and TIP4P) show considerably better agreement with the experimental data than the ones which exhibit less structured O–O correlation functions (SPC and TIP3P). In the second part of the paper we calculate the hydrophobic interaction between xenon particles directly from a series of 60 ns simulation runs. We find that the temperature dependence of the association is to a large extent related to the strength of the solvation entropy. Nevertheless, differences between the models seem to require a more detailed molecular picture. The TIP5P model shows by far the strongest temperature dependence. The suggested density rescaling is also applied to the chemical potential in the xenon–xenon contact-pair configuration, indicating the presence of a temperature where the hydrophobic interaction turns into purely repulsive. The predicted association for xenon in real water suggests the presence of a strong variation with temperature, comparable to the behavior found for TIP5P water. Comparing different water models and experimental data we conclude that a proper description of density effects is an important requirement for a water model to account correctly for the correct description of the hydrophobic effects. A water model exhibiting a density maximum at the correct temperature is desirable.
Ab initio studies of alkyl radical reactions: Combination and disproportionation reactions of CH3 with C2H5, and the decomposition of chemically activated C3H8
Authors: Zhu R. S. , Xu Z. F. , Lin M. C.
Published: March 2004

This paper reports the first quantitative ab initio prediction of the disproportionation/combination ratio of alkyl+alkyl reactions using CH3+C2H5 as an example. The reaction has been investigated by the modified Gaussian-2 method with variational transition state or Rice–Ramsperger–Kassel–Marcus calculations for several channels producing (1) CH4+CH2CH2, (2) C3H8, (3) CH4+CH3CH, (4) H2+CH3CHCH2, (5) H2+CH3CCH3, and (6) C2H6+CH2 by H-abstraction and association/decomposition mechanisms through singlet and triplet potential energy paths. Significantly, the disproportionation reaction (1) producing CH4+C2H4 was found to occur primarily by the lowest energy path via a loose hydrogen-bonding singlet molecular complex, H3C⋅⋅HC2H4, with a 3.5 kcal/mol binding energy and a small decomposition barrier (1.9 kcal/mol), instead of a direct H-abstraction process. Bimolecular reaction rate constants for the formation of the above products have been calculated in the temperature range 300–3000 K. At 1 atm, formation of C3H8 is dominant below 1200 K. Over 1200 K, the disproportionation reaction becomes competitive. The sum of products (3)–(6) accounts for less than 0.3% below 1500 K and it reaches around 1%–4% above 2000 K. The predicted rate constant for the disproportionation reaction with multiple reflections above the complex well, k1=5.04×T0.41 exp(429/T) at 200–600 K and k1=1.96×10−20 T2.45 exp(1470/T) cm3 molecule−1 s−1 at 600–3000 K, agrees closely with experimental values. Similarly, the predicted high-pressure rate constants for the combination reaction forming C3H8 and its reverse dissociation reaction in the temperature range 300–3000 K, k2∞=2.41×10−10 T−0.34 exp(259/T) cm3 molecule−1 s−1 and k−2∞=8.89×1022 T−1.67exp(−46 037/T) s−1, respectively, are also in good agreement with available experimental data.
Homogeneous nucleation of droplets from supersaturated vapor in a closed system
Authors: Kožı́šek Zdeněk , Sato Kyotaka , Demo Pavel , Sveshnikov Alexei M.
Published: March 2004

Kinetic equations describing homogeneous nucleation kinetics within standard model are solved numerically under the condition of a constant number of molecules in the considered system. It has consequences to decrease the supersaturation of the supersaturated vapor during the process of the formation of small droplets of a new phase. The decrease of supersaturation occurs in a short time and reaches some value which remains unchanged for a relatively long time (quasistationary regime), especially at lower initial supersaturations. This time interval decreases with increasing value of the initial supersaturation. In the quasistationary regime the nucleation rate reaches its stationary value. At higher initial supersaturation, the rate of formation of nuclei goes to some maximum value corresponding to the stationary nucleation rate and then decreases with time due to the decrease of supersaturation.
Integral equation study of a Stockmayer fluid adsorbed in polar disordered matrices
Authors: Spöler C. , Klapp S. H. L.
Published: March 2004

Based on replica integral equations in the (reference) hypernetted chain approximation we investigate the structural features and phase properties of a dipolar Stockmayer fluid confined to a disordered dipolar matrix. The integral equations are applied to the homogeneous high-temperature phase where the system is globally isotropic. At low densities we find the influence of dipolar interactions between fluid (f) and matrix (m) particles to be surprisingly similar to the previously investigated effect of attractive isotropic (fm) interactions: the critical temperature of the vapor–liquid transition decreases with increasing (fm) coupling, while the critical density increases. The anisotropic nature of the dipolar (fm) interactions turns out to play a more dominant role at high fluid densities where we observe a pronounced sensitivity in the dielectric constant and a strong degree of local orientational ordering of the fluid particles along the local fields generated by the matrix. Moreover, an instability of the dielectric constant, which is a precursor of ferroelectric ordering occurring both in bulk Stockmayer fluids and in fluids in nonpolar matrices, is observed only for very small dipolar (fm) couplings.
Competitive C–H and O–D bond fission channels in the UV photodissociation of the deuterated hydroxymethyl radical CH2OD
Authors: Feng Lin , Demyanenko Andrey V. , Reisler Hanna
Published: March 2004

Photodissociation studies of the CH2OD radical in the region 28 000–41 000 cm−1 (357–244 nm), which includes excitation to the 3s, 3px, and 3pz states, are reported. H and D photofragments are monitored by using resonance-enhanced multiphoton ionization (REMPI) from the onset of H formation at ∼30 500 cm−1 to the origin band region of the 3pz(2A″)←1 2A″ transition at 41 050 cm−1. Kinetic energy distributions P(ET) and recoil anisotropy parameters as a function of kinetic energy, βeff(ET), are determined by the core sampling technique for the channels producing H and D fragments. Two dissociation channels are identified: (I) D+CH2O and (II) H+CHOD. The contribution of channel II increases monotonically as the excitation energy is increased. Based on the calculations of Hoffmann and Yarkony [J. Chem. Phys. 116, 8300 (2002)], it is concluded that conical intersections between 3s and the ground state determine the final branching ratio even when initial excitation accesses the 3px and 3pz states. The different βeff values obtained for channels I and II (−0.7 and ∼0.0, respectively) are attributed to the different extents of out-of-plane nuclear motions in the specific couplings between 3s and the ground state (of A′ and A″ symmetry, respectively) that lead to each channel. The upper limit to the dissociation energy of the C–H bond, determined from P(ET), is D0(C–H)=3.4±0.1 eV (79±2 kcal/mol). Combining this value with the known heats of formation of H and CH2OD, the heat of formation of CHOD is estimated at ΔHf0(CHOD)=24±2 kcal/mol.
Improving the accuracy of interpolated potential energy surfaces by using an analytical zeroth-order potential function
Authors: Kawano Akio , Guo Yin , Thompson Donald L. , Wagner Albert F. , Minkoff Michael
Published: March 2004

We present a method for improving the accuracy and efficiency of interpolation methods, in which an analytical zeroth-order potential-energy surface is employed as a reference surface. To investigate and test the method, we apply it to hydrogen peroxide where there exists an accurate analytical surface which we take as the “exact” surface for obtaining the energies and derivatives for fitting and assessing the accuracy. Examples are given for four-dimensional and six-dimensional surfaces interpolated by using either the modified Shepard or second-degree interpolating moving least-squares approach, with comparisons for cases with and without using the zeroth-order potential.
Trans-1-chloro-2-fluoroethylene: Microwave spectra and anharmonic force field
Authors: Cazzoli Gabriele , Puzzarini Cristina , Gambi Alberto
Published: March 2004

For the first time the millimeter-wave spectra of the trans-ClHC35=CHF and trans-ClHC37=CHF isotopomers have been observed in natural abundance. Many ΔJ=0, ±1 ΔK−1=+1 transitions for ClHC35=CHF and ΔJ=0 ΔK−1=+1 transitions for ClHC37=CHF have been detected and assigned. This allowed us to accurately determine the vibrational ground-state rotational constants, quartic and some sextic centrifugal distortion constants, and nuclear quadrupole coupling constants for both Cl35 and Cl37. The experimental investigation has been supported by highly accurate theoretical predictions. As far as ab initio computations are concerned, the complete set of cubic and quartic force constants have been evaluated by numerical differentiation of the analytic second-order Møller–Plesset many-body perturbation theory/correlation consistent polarized valence triple zeta second derivatives. The anharmonic part of the force field completes the theoretical study on the equilibrium structure, dipole moment, chlorine quadrupolar tensor, and harmonic force field previously carried out by the same authors.
Saturated adsorption of CO and coadsorption of CO and O2 on AuN− (N=2–7) clusters
Authors: Yuan D. W. , Zeng Zhi
Published: March 2004

A first-principles quantum chemistry method, based on the Kohn–Sham density-functional theory, is used to investigate the adsorption of CO and O2 on small gas-phase gold cluster anions. The saturated adsorption of carbon monoxide on gold cluster anions AuN− (N=2–7) is discussed. The adsorption ability of CO reduces with the increase of the number of CO molecules bound to gold cluster anions, resulting in saturated adsorption at a certain amount of absorbed CO molecules, which is determined by geometric and electronic properties of gold clusters cooperatively. The effect of CO preadsorption on the electronic properties of gold cluster anions depends on the cluster size and the number of adsorbed CO, and the vertical detachment energies of CO-adsorbed gold cluster anions show a few changes with respect to corresponding pure gold cluster anions. The results indicate that the impinging adsorption of CO molecules may lead to geometry structure transformation on Au3− cluster. For the coadsorption of CO and O2 on Au2−, Au3− isomers, Au4−, and Au6−, we describe the cooperative adsorption between CO and O2, and find that the O2 dissociation is difficult on gas-phase gold cluster anions even with the preadsorption of CO.
Hybrid atomistic-coarse-grained treatment of thin-film lubrication. I
Authors: Wu Z.-B. , Diestler D. J. , Feng R. , Zeng X. C.
Published: March 2004

A technique that melds an atomistic description of the interfacial region with a coarse-grained description of the far regions of the solid substrates is presented and applied to a two-dimensional model contact consisting of planar solid substrates separated by a monolayer fluid film. The hybrid method yields results in excellent agreement with the “exact” (i.e., fully atomistic) results. The importance of a proper accounting for the elastic response of the substrates, which is reliably and efficiently accomplished through coarse-graining of the far regions, is demonstrated.
Spatial Small Worlds: New Geographic Patterns for an Information Economy
Authors: Gorman Sean P , Kulkarni Rajendra
Published: March 2004

Networks are structures that pervade many natural and manmade phenomena. Recent findings have characterized many networks as not random chaotic structures but as efficient complex formations. Current research has examined complex networks as largely a nonspatial phenomenon. Location, distance, and geography, though, are all vital aspects of a wide variety of networks. The authors examine the US portion of Internet infrastructure as a complex network and the role distance and geography play in its formation. From these findings implications are drawn on the economic, political, national security, and technological impacts of network formation and evolution in an information economy.
Distance Transforms as a New Tool in Spatial Analysis, Urban Planning, and GIS
Authors: de Smith Michael J
Published: March 2004

Many spatial datasets and spatial problems can be described with reference to regular lattice frameworks rather than continuous space. Examples include: raster scan and digital elevation model data, digital images, cost surfaces, cellular automata models, swarm models, and many others. This raises the question as to how distances should be measured in such cases and to what extent these relate to continuous space metrics. In this paper I show that a set of image processing algorithms known as distance transforms (DTs) may be applied to such datasets and can be extended to solve a wide range of 2D and 3D optimisation problems. These extended versions of the standard DT procedure have applications in many areas including location theory, path determination, planning, and decision support. As such I argue that they warrant consideration for inclusion as a standard set of tools within modern GIS and spatial analysis software packages. Sample pseudo-code for the transforms discussed is included in an appendix.
Using the Sleuth Urban Growth Model to Simulate the Impacts of Future Policy Scenarios on Urban Land Use in the Baltimore-Washington Metropolitan Area
Authors: Jantz Claire A , Goetz Scott J , Shelley Mary K
Published: March 2004

Declining water quality in the Chesapeake Bay estuary is in part the result of disruptions in the hydrological system caused by urban and suburban development throughout its 167000 km2 watershed. A modeling system that could provide regional assessments of future development and explore the potential impacts of different regional management scenarios would be useful for a wide range of applications relevant to the future health of the Bay and its tributaries. We describe and test a regional predictive modeling system that could be used to meet these needs. An existing cellular automaton model, SLEUTH, was applied to a 23 700 km2 area centered on the Washington-Baltimore metropolitan region, which has experienced rapid land-use change in recent years. The model was calibrated using a historic time series of developed areas derived from remote sensing imagery, and future growth was projected out to 2030 assuming three different policy scenarios: (1) current trends, (2) managed growth, and (3) ecologically sustainable growth. The current trends scenario allowed areas on the urban fringe that are currently rural or forested to be developed, which would have implications for water quality in the Chesapeake Bay and its tributaries. The managed growth and ecologically sustainable scenarios produced growth patterns that were more constrained and which consumed less natural resource land. This application of the SLEUTH model demonstrates an ability to address a range of regional planning issues, but spatial accuracy and scale sensitivity are among the factors that must be further considered for practical application.
Integrating Affordable Housing within Market-Rate Developments: The Design Dimension
Authors: Tiesdell Steven
Published: March 2004

Current planning policy in England enables local planning authorities to require housing developments above a certain size to include a proportion of ‘affordable’ housing. The policy has social objectives (that is, to create ‘mixed’ communities and reduce the potential for the ‘ghettoisation’ of affordable housing) and financial objectives (that is, to shift the cost of providing social housing to the private sector). Although aspects of the policy have been the subject of research the design issues have yet to be fully investigated. Viewed from a development process perspective, the key design question is how layout and design decisions are affected by the developer's perception (or market experience) that the inclusion of affordable units has a detrimental effect on the market-rate housing. To aid further research, the author develops a classification of design strategies and outcomes necessitated by the inclusion of an element of affordable housing.
Determinants of Land-Use Change Patterns in the Netherlands
Authors: Verburg Peter H , van Eck Jan R Ritsema , de Nijs Ton C M , Dijst Martin J , Schot Paul
Published: March 2004

Land-use-change patterns are the result of the complex interaction between the human and the physical environment. Case studies of the determinants of land-use change can help to analyse which theory is appropriate in a particular region and stimulate the development of new theoretic understandings. In this paper an empirical method is presented to analyse the pattern of land-use change that allows a wide range of factors, from different disciplines, to contribute to the explanation of land-use change. The method is applied to the Netherlands, based on an extensive database of land-use change and its potential determinants. Historic as well as recent land-use changes are studied. Historic land-use change is related mainly to the variation in the biophysical environment. Levels of explanation are low because of the inability to address the temporal variation in location factors. For the recent changes in land use high levels of explanation are obtained. The most important changes during this period are expansions of residential, industrial/commercial, and recreational areas. The location of these changes can be explained by a combination of accessibility measures, spatial policies, and neighbourhood interactions. On the basis of these results it is possible to define priority topics for in-depth analysis of land-use-change processes and suggest factors, relations, and processes that need to be included in dynamic land-use-change models that support land-use-planning policies.
Low-density koala (Phascolarctos cinereus) populations in the mulgalands of south-west Queensland. IV. Abundance and conservation status
Authors: Sullivan B. J. , Baxter G. S. , Lisle A. T. , Pahl L. , Norris W. M.
Published: March 2004

Urban encroachment on dense, coastal koala populations has ensured that their management has received increasing government and public attention. The recently developed National Koala Conservation Strategy calls for maintenance of viable populations in the wild. Yet the success of this, and other, conservation initiatives is hampered by lack of reliable and generally accepted national and regional population estimates. In this paper we address this problem in a potentially large, but poorly studied, regional population in the State that is likely to have the largest wild populations. We draw on findings from previous reports in this series and apply the faecal standing-crop method (FSCM) to derive a regional estimate of more than 59 000 individuals. Validation trials in riverine communities showed that estimates of animal density obtained from the FSCM and direct observation were in close agreement. Bootstrapping and Monte Carlo simulations were used to obtain variance estimates for our population estimates in different vegetation associations across the region. The most favoured habitat was riverine vegetation, which covered only 0.9% of the region but supported 45% of the koalas. We also estimated that between 1969 and 1995 ~30% of the native vegetation associations that are considered as potential koala habitat were cleared, leading to a decline of perhaps 10% in koala numbers. Management of this large regional population has significant implications for the national conservation of the species: the continued viability of this population is critically dependent on the retention and management of riverine and residual vegetation communities, and future vegetation-management guidelines should be cognisant of the potential impacts of clearing even small areas of critical habitat. We also highlight eight management implications.
Galanin acts as a neuroprotective factor to the hippocampus
Authors: Elliott-Hunt Caroline R. , Marsh Barnaby , Bacon Andrea , Pope Robert , Vanderplank Penny , Wynick David
Published: March 2004

The expression of the neuropeptide galanin is markedly up-regulated in many areas of the central and peripheral nervous system after injury. We have recently demonstrated that peripheral sensory neurons depend on galanin for neurite extension after injury, mediated by activation of the second galanin receptor subtype (GALR2). We therefore hypothesized that galanin might also act in a similar manner in the CNS, reducing cell death in hippocampal models of excitotoxicity. Here we report that galanin acts an endogenous neuroprotective factor to the hippocampus in a number ofin vivoandin vitromodels of injury. Kainate-induced hippocampal cell death was greater in both the CA1 and CA3 regions of galanin knockout animals than in WT controls. Similarly, exposure to glutamate or staurosporine induced significantly more neuronal cell death in galanin knockout organotypic and dispersed primary hippocampal cultures than in WT controls. Conversely, less cell death was observed in the hippocampus of galanin overexpressing transgenic animals after kainate injection and in organotypic cultures after exposure to staurosporine. Further, exogenous galanin or the previously described high-affinity GALR2 agonist, both reduced cell death when coadministered with glutamate or staurosporine in WT cultures. These results demonstrate that galanin acts an endogenous neuroprotective factor to the hippocampus and imply that a galanin agonist might have therapeutic uses in some forms of brain injury.
Stable association between strains of
Mycobacterium tuberculosis
and their human host populations
Authors: Hirsh Aaron E. , Tsolaki Anthony G. , DeRiemer Kathryn , Feldman Marcus W. , Small Peter M.
Published: March 2004

Mycobacterium tuberculosis
is an important human pathogen in virtually every part of the world. Here we investigate whether distinct strains of
M. tuberculosis
infect different human populations and whether associations between host and pathogen populations are stable despite global traffic and the convergence of diverse strains of the pathogen in cosmopolitan urban centers. The recent global movement and transmission history of 100
M. tuberculosis
isolates was inferred from a molecular epidemiologic study of tuberculosis that spans 12 years. Genetic relationships among these isolates were deduced from the distribution of large genomic deletions, which were identified by DNA microarray and confirmed by PCR and sequence analysis. Phylogenetic analysis of these deletions indicates that they are unique event polymorphisms and that horizontal gene transfer is extremely rare in
M. tuberculosis
. In conjunction with the epidemiological data, phylogenies reveal three large phylogeographic regions. A host's region of origin is predictive of the strain of tuberculosis he or she carries, and this association remains strong even when transmission takes place in a cosmopolitan urban center outside of the region of origin. Approximate dating of the time since divergence of East Asian and Philippine clades of
M. tuberculosis
suggests that these lineages diverged centuries ago. Thus, associations between host and pathogen populations appear to be highly stable.
Protein kinetics: Structures of intermediates and reaction mechanism from time-resolved x-ray data
Authors: Schmidt Marius , Pahl Reinhard , Srajer Vukica , Anderson Spencer , Ren Zhong , Ihee Hyotcherl , Rajagopal Sudarshan , Moffat Keith
Published: March 2004

We determine the number of authentic reaction intermediates in the later stages of the photocycle of photoactive yellow protein at room temperature, their atomic structures, and a consistent set of chemical kinetic mechanisms, by analysis of a set of time-dependent difference electron density maps spanning the time range from 5 μs to 100 ms. The successful fit of exponentials to right singular vectors derived from a singular value decomposition of the difference maps demonstrates that a chemical kinetic mechanism holds and that structurally distinct intermediates exist. We identify two time-independent difference maps, from which we refine the structures of the corresponding intermediates. We thus demonstrate how structures associated with intermediate states can be extracted from the experimental, time-dependent crystallographic data. Stoichiometric and structural constraints allow the exclusion of one kinetic mechanism proposed for the photocycle but retain other plausible candidate kinetic mechanisms.
Homeostatic scaling of neuronal excitability by synaptic modulation of somatic hyperpolarization-activated
I
h
channels
Authors: van Welie Ingrid , van Hooft Johannes A. , Wadman Wytse J.
Published: March 2004

The hyperpolarization-activated cation current (
I
h
) plays an important role in determining membrane potential and firing characteristics of neurons and therefore is a potential target for regulation of intrinsic excitability. Here we show that an increase in AMPA-receptor-dependent synaptic activity induced by α-latrotoxin or glutamate application as well as direct depolarization results in an increase in
I
h
recorded from cell-attached patches in hippocampal CA1 pyramidal neurons. This mechanism requires Ca
2+
influx but not increased levels of cAMP. Artificially increasing
I
h
by using a dynamic clamp during whole-cell current clamp recordings results in reduced firing rates in response to depolarizing current injections. We conclude that modulation of somatic
I
h
represents a previously uncharacterized mechanism of homeostatic plasticity, allowing a neuron to control its excitability in response to changes in synaptic activity on a relatively short-term time scale.
Functional association between Wwox tumor suppressor protein and p73, a p53 homolog
Authors: Aqeilan Rami I. , Pekarsky Yuri , Herrero Juan J. , Palamarchuk Alexey , Letofsky Jean , Druck Teresa , Trapasso Francesco , Han Shuang-Yin , Melino Gerry , Huebner Kay , Croce Carlo M.
Published: March 2004

The
WWOX
gene is a recently cloned tumor suppressor gene that spans the
FRA16D
fragile region. Wwox protein contains two WW domains that are generally known to mediate protein–protein interaction. Here we show that Wwox physically interacts via its first WW domain with the p53 homolog, p73. The tyrosine kinase, Src, phosphorylates Wwox at tyrosine 33 in the first WW domain and enhances its binding to p73. Our results further demonstrate that Wwox expression triggers redistribution of nuclear p73 to the cytoplasm and, hence, suppresses its transcriptional activity. In addition, we show that cytoplasmic p73 contributes to the proapoptotic activity of Wwox. Our findings reveal a functional cross-talk between p73 and Wwox tumor suppressor protein.
Protection against zinc toxicity by metallothionein and zinc transporter 1
Authors: Palmiter Richard D.
Published: March 2004

Cells protect themselves from zinc toxicity by inducing proteins such as metallothionein (MT) that bind it tightly, by sequestering it in organelles, or by exporting it. In this study, the interplay between zinc binding by MT and its efflux by zinc transporter 1 (ZnT1) was examined genetically. Inactivation of the
Znt1
gene in baby hamster kidney (BHK) cells that do not express their
Mt
genes results in a zinc-sensitive phenotype and a high level of “free” zinc. Restoration of
Mt
gene expression increases resistance to zinc toxicity ≈4-fold, but only slightly reduces free zinc levels. Expression of ZnT1 provides greater protection (≈7-fold) and lowers free zinc substantially. Selection for zinc resistance in BHK cells that cannot synthesize either MT or ZnT1 is ineffective. However, parental BHK cells that grow in high concentrations (>500 μM) of zinc can be selected; these cells have amplified their endogenous
Znt1
genes. The Z
nt1
gene is also amplified in zinc-resistant mouse cells that cannot induce their
Mt
genes. However, if
Mt
genes can be expressed, then they are preferentially amplified. Thus, both ZnT1 and MT genes contribute to zinc resistance in BHK cells, whereas ZnT1 plays a larger role in regulating free zinc levels.
Differential expression patterns of the hox gene are associated with differential growth of insect hind legs
Authors: Mahfooz Najmus S. , Li Hua , Popadić Aleksandar
Published: March 2004

Diversification of leg appendages is one of the hallmarks of morphological evolution in insects. In particular, insect hind (T3) legs exhibit a whole spectrum of morphological diversification, ranging from uniform to extremely modified. To elucidate the developmental basis of T3 leg evolution, we have examined the expression patterns of two homeotic genes,
Ultrabithorax
and
abdominal-A
(collectively referred to as
UbdA
), in a broad range of species. First, our results show that
UbdA
expression in hemimetabolous insects is localized only in specific T3 leg segments undergoing differential growth (compared to their foreleg counterparts). In contrast, in basal hexapod and insect lineages, the absence of the
UbdA
signal coincides with uniform leg morphology. The same situation exists in first instar larvae of holometabolous insects, in which absence of
UbdA
expression in the embryonic T3 legs is associated with the lack of larval T3 leg diversification. Second, there is a clear difference in the timing of expression between species with greatly enlarged T3 leg, such as crickets and grasshoppers, and species that exhibit more moderate enlargement of hind legs, such as mantids and cockroaches. In the former, the
UbdA
expression starts much earlier, coinciding with the elongation of T3 limb buds. In the latter, however, the
UbdA
expression starts at much later stages of development, coinciding with the establishment of distinct leg segments. These results suggest that diversification of insect hind legs was influenced by changes in both the
spatial
and
temporal
regulation of the
UbdA
expression.
Cell Surface Organization of Stress-inducible Proteins ULBP and MICA That Stimulate Human NK Cells and T Cells via NKG2D
Authors: Eleme Konstantina , Taner Sabrina B. , Önfelt Björn , Collinson Lucy M. , McCann Fiona E. , Chalupny N. Jan , Cosman David , Hopkins Colin , Magee Anthony I. , Davis Daniel M.
Published: March 2004

Cell surface proteins major histocompatibility complex (MHC) class I–related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein–tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for the organization of these proteins, ULBP1, 2, and 3 and MICA are lipid modified. ULBP1, 2, and 3 are GPI anchored, and we demonstrate here that MICA is S-acylated. Finally, expression of a truncated form of MICA that lacks the putative site for S-acylation and the cytoplasmic tail can be expressed at the cell surface, but is unable to activate NK cells.
Defining transcription modules using large-scale gene expression data
Authors: Ihmels Jan , Bergmann Sven , Barkai Naama
Published: March 2004

Motivation: Large-scale gene expression data comprising a variety of cellular conditions hold the promise of a global view on the transcription program. While conventional clustering algorithms have been successfully applied to smaller datasets, the utility of many algorithms for the analysis of large-scale data is limited by their inability to capture combinatorial and condition-specific co-regulation. In addition, there is an increasing need to integrate the rapidly accumulating body of other high-throughput biological data with the expression analysis. In a previous work, we introduced the signature algorithm, which overcomes the problems of conventional clustering and allows for intuitive integration of additional biological data. However, this approach is constrained by the comprehensiveness of relevant external data and its lacking ability to capture hierarchical modularity.

Methods: We present a novel method for the analysis of large-scale expression data, which assigns genes into context-dependent and potentially overlapping regulatory units. We introduce the notion of a transcription module as a self-consistent regulatory unit consisting of a set of co-regulated genes as well as the experimental conditions that induce their co-regulation. Self-consistency is defined by a rigorous mathematical criterion. We propose an efficient algorithm to identify such modules, which is based on the iterative application of the signature algorithm. A threshold parameter that determines the resolution of the modular decomposition is introduced.

Results: The method is applied systematically to over 1000 expression profiles of the yeast Saccharomyces cerevisiae, and the results are presented using two complementary visualization schemes we developed. The average biological coherence, as measured by the conservation of putative cis-regulatory motifs between four related yeast species, is higher for transcription modules than for clusters identified by other methods applied to the same dataset. Our method is related to singular value decomposition (SVD) and to the pairwise average linkage clustering algorithm. It extends SVD by filtering out noise in the expression data and offering variable resolution to reveal hierarchical organization. It furthermore has the advantage over both methods of capturing overlapping modules in the presence of combinatorial regulation.

Supplementary information:  http://www.weizmann.ac.il/~barkai/modules
A comparison of cluster analysis methods using DNA methylation data
Authors: Siegmund Kimberly D. , Laird Peter W. , Laird-Offringa Ite A.
Published: March 2004

Motivation: Aberrant DNA methylation is common in cancer. DNA methylation profiles differ between tumor types and subtypes and provide a powerful diagnostic tool for identifying clusters of samples and/or genes. DNA methylation data obtained with the quantitative, highly sensitive MethyLight technology is not normally distributed; it frequently contains an excess of zeros. Established tools to analyze this type of data do not exist. Here, we evaluate a variety of methods for cluster analysis to determine which is most reliable.

Results: We introduce a Bernoulli–lognormal mixture model for clustering DNA methylation data obtained using MethyLight. We model the outcomes using a two-part distribution having discrete and continuous components. It is compared with standard cluster analysis approaches for continuous data and for discrete data. In a simulation study, we find that the two-part model has the lowest classification error rate for mixture outcome data compared with other approaches. The methods are illustrated using DNA methylation data from a study of lung cancer cell lines. Compared with competing hierarchical clustering methods, the mixture model approaches have the lowest cross-validation error for detecting lung cancer subtype (non-small versus small cell). The Bernoulli–lognormal mixture assigns observations to subgroups with the lowest uncertainty.

Availability: Software is available upon request from the authors.

Supplementary information:  http://www-rcf.usc.edu/~kims/SupplementaryInfo.html
Supervised cluster analysis for microarray data based on multivariate Gaussian mixture
Authors: Qu Yi , Xu Shizhong
Published: March 2004

Motivation: Grouping genes having similar expression patterns is called gene clustering, which has been proved to be a useful tool for extracting underlying biological information of gene expression data. Many clustering procedures have shown success in microarray gene clustering; most of them belong to the family of heuristic clustering algorithms. Model-based algorithms are alternative clustering algorithms, which are based on the assumption that the whole set of microarray data is a finite mixture of a certain type of distributions with different parameters. Application of the model-based algorithms to unsupervised clustering has been reported. Here, for the first time, we demonstrated the use of the model-based algorithm in supervised clustering of microarray data.

Results: We applied the proposed methods to real gene expression data and simulated data. We showed that the supervised model-based algorithm is superior over the unsupervised method and the support vector machines (SVM) method.

Availability: The program written in the SAS language implementing methods I–III in this report is available upon request. The software of SVMs is available in the website http://svm.sdsc.edu/cgi-bin/nph-SVMsubmit.cgi
Quantitative characterization of the transcriptional regulatory network in the yeast cell cycle
Authors: Chen Hong-Chu , Lee Hsiao-Ching , Lin Tsai-Yun , Li Wen-Hsiung , Chen Bor-Sen
Published: March 2004

Motivation: Genome-wide gene expression programs have been monitored and analyzed in the yeast Saccharomyces cerevisiae, but how cells regulate global gene expression programs in response to environmental changes is still far from being understood. We present a systematic approach to quantitatively characterize the transcriptional regulatory network of the yeast cell cycle. For the interpretative purpose, 20 target genes were selected because their expression patterns fluctuated in a periodic manner concurrent with the cell cycle and peaked at different phases. In addition to the most significant five possible regulators of each specific target gene, the expression pattern of each target gene affected by synergy of the regulators during the cell cycle was characterized. Our first step includes modeling the dynamics of gene expression and extracting the transcription rate from a time-course microarray data. The second step embraces finding the regulators that possess a high correlation with the transcription rate of the target gene, and quantifying the regulatory abilities of the identified regulators.

Results: Our network discerns not only the role of the activator or repressor for each specific regulator, but also the regulatory ability of the regulator to the transcription rate of the target gene. The highly coordinated regulatory network has identified a group of significant regulators responsible for the gene expression program through the cell cycle progress. This approach may be useful for computing the regulatory ability of the transcriptional regulatory networks in more diverse conditions and in more complex eukaryotes.

Supplementary information: Matlab code and test data are available at http://www.ee.nthu.edu.tw/~bschen/quantitative/regulatory_network.htm
A novel approach for increasing sensitivity and correcting saturation artifacts of radioactively labeled cDNA arrays
Authors: Querec Troy D. , Stoyanova Radka , Ross Eric , Patriotis Christos
Published: March 2004

Motivation: The radioactivity labeled DNA array platform is a robust and accurate way for a high-throughput measurement of gene expression levels in biological samples. Despite its high degree of sensitivity and reproducibility, this platform has several sources of variation. These are related to the presence of saturation effects in the array images and impede the degree of accuracy at which gene expression levels are determined.

Results: Here we describe a simple, but effective, approach for combining expression data from a series of autoradiographic exposures of variable length. This technique increases the sensitivity of this array platform by detecting low-expressed genes at longer exposures. It also improves the measurement accuracy of highly abundant genes by considering only values from the linear portion of dependency between the exposure times and gene intensities. As a result, the described approach improves the outcome of the subsequent steps of array data normalization and mining.
Defining 3D residue environment in protein structures using SCORPION and FORMIGA
Authors: Higa R. H. , Oliveira A. G. , Horita L. G. , Miura R. T. , Inoue M. K. , Kuser P. R. , Mancini A. L. , Yamagishi M. E. B. , Togawa R. C. , Neshich G.
Published: March 2004

Summary: Two web-based applications to analyze amino acids three-dimensional (3D) local environment within protein structures—SCORPION and FORMIGA—are presented. SCORPION and FORMIGA produce a graphical presentation for simple statistical data showing the frequency of residue occurrence within a given sphere (defined here as the 3D contacts). The center of that sphere is placed at the Cα and at the last heavy atom in the side chain of the selected amino acid. Further depth of detail is given in terms of a secondary structure to which the profiled amino acid belongs. Results obtained with those two applications are relevant for estimating the importance of the amino acid 3D local environment for protein folding and stability. Effectively, SCORPION and FORMIGA construct knowledge-based force fields. The difference between SCORPION and FORMIGA is in that the latter operates on protein interfaces, while the former only functions for a single protein chain. Both applications are implemented as stand-alone components of STING Millennium Suite.

Availability:  http://sms.cbi.cnptia.embrapa.br/SMS, http://trantor.bioc.columbia.edu/SMS, http://mirrors.rcsb.org/SMS, http://www.es.embnet.org/SMS and http://www.ar.embnet.org/SMS. {options: Scorpion, Formiga}
Repair-FunMap: a functional database of proteins of the DNA repair systems
Authors: Wen Liting , Feng Jin-An
Published: March 2004

Summary: Repair-FunMap is a functional database of the DNA repair systems. This database contains not only the proteins directly involved in DNA repair, but also the proteins that interact with the DNA repair proteins. A protein interaction network associated with the human DNA repair processes was established according to the functional relationship between proteins in the database. This network represents the current knowledge on the intrinsic signaling pathways related to DNA repair. The Repair-FunMap could become an essential resource center for cancer research, providing clues to understanding the inter-relationship between proteins in the network, and to building scientific models of the DNA repair processes.

Availability:  http://astro.temple.edu/~feng/Servers/BioinformaticServers.htm
Connexin 26 and Connexin 30 Mutations in Children with Nonsyndromic Hearing Loss
Authors: Erbe Christy B. , Harris Kevin C. , Runge‐Samuelson Christina L. , Flanary Valerie A. , Wackym Phillip Ashley
Published: March 2004

Objectives/Hypothesis Mutations in the connexin 26 (Cx26) or gap junction beta 2 gene are the leading cause of hereditary nonsyndromic sensorineural hearing loss in Caucasians. The Cx26 coding region of 68 children with nonsyndromic sensorineural hearing loss was sequenced to determine the frequency and type of Cx26 mutations in this population. Screening was also performed for a common connexin 30 (Cx30) or gap junction beta 6 mutation (del [GJB6‐D13S1830]). Children also underwent audiological testing to determine whether any correlation exists between Cx26 mutations and severity of hearing loss.

Study Design In all, 68 children with nonsyndromic sensorineural hearing loss were screened for Cx26 and Cx30 mutations by polymerase chain reaction and direct sequencing.

Methods Genomic DNA was amplified by polymerase chain reaction using primers that flank the entire Cx26 coding region. Screening for the 342‐kb Cx30 deletion was performed using primers that amplified the breakpoint junction of the deletion. The amplicons were then sequenced in both directions and analyzed for mutations. Audiometric testing, including pure‐tone audiometry and auditory evoked brainstem response, was also performed to determine the degree of hearing loss.

Results Twenty‐seven of 68 children tested had mutations in Cx26 with 35delG being the most prevalent. Ten additional Cx26 mutations were detected including a novel compound heterozygote. Two children were heterozygous for the Cx30 del (GJB6‐D13S1830) mutation.

Conclusion Cx26 and Cx30 mutations were present in 41.2% of children tested in the study population. Audiometric data supported previous studies demonstrating a greater degree of hearing loss in subjects who are homozygous for the 35delG mutation.
Protective Effect of Corticosteroid against the Cytotoxicity of Aminoglycoside Otic Drops on Isolated Cochlear Outer Hair Cells
Authors: Park Seong Kook , Choi Dukjoo , Russell Paul , John Earnest O. , Jung Timothy T. K.
Published: March 2004

Objectives Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanic membrane perforation or tympanostomy tube. Many studies demonstrated the ototoxicity of aminoglycoside. In our previous study, we observed that gentamicin (GM), when activated with liver extract, demonstrated significant cytotoxicity. The purpose of this study was to assess the protective effect of corticosteroid against the cytotoxicity of GM and tobramycin drops using isolated cochlear outer hair cells (OHCs) in vitro with liver extract.

Methods OHCs from adult chinchilla cochleae were exposed to standard bathing solution, liver extract alone, and aminoglycoside otic drops with and without corticosteroid and liver extract. All experiments were performed at an osmolality of 305 ± 5 mOsm, at room temperature, and for up to 60 minutes. The images of OHCs were recorded using an inverted microscope and analyzed on the Image Pro‐Plus 3.0 program. Time to cell death and change of cell length were measured and analyzed.

Results The time to cell death and percent change in cell length observed was significantly longer in the GM + liver extract + dexamethasone group than the GM + liver extract group (P < .05). The Tobradex + liver extract group showed an insignificant increase in percent change of cell length (P > .05) and significantly increased time to cell death than the tobramycin + liver extract group (P < .05).

Conclusion This study demonstrated that dexamethasone significantly reduced aminoglycoside cytotoxicity.