bluuebunny/crossref_metadata_2025 huggingface dataset:
XPS study of electron‐induced surface processes in trimethylsilane‐covered Ge(100) surfaces
Authors: Wang P. W. , Qi Y. , Craig J. H.
Published: November 2002

X‐ray photoelectron spectroscopy (XPS) was used to study the effects of electron beam irradiation of a multilayer film of trimethylsilane on a clean Ge(100) surface at −150°C. Core level C 1s, Si 2p, and Ge 3d photoelectrons were monitored at the same experimental conditions after various electron fluences. Electron irradiation is observed to cause an increase in the relative silicon surface concentration with a corresponding decrease in the carbon concentration. No change was evident in the surface germanium concentration, although electron irradiation resulted in an increasing concentration of C–Ge bonds with time. Simultaneously, the concentration of C–Si bonds decreased as a function of irradiation time. Growth of silicon islands is postulated as a possible explanation for this observation. The possible silicon island growth proposal is supported by the observed gradual decrease in concentration of Si–Si bonds, which would occur as the fraction of the surface covered by silicon decreases. Copyright © 2002 John Wiley & Sons, Ltd.
Relationship between the structure of polymers with well‐defined fluorocarbon segmental lengths and the formation of secondary ions in SIMS
Authors: Zhou Hui , Chan Chi‐Ming , Weng Lu‐Tao , Ng Kai‐Mo , Li Lin
Published: November 2002

A series of fluorinated polymers were studied using time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) to investigate the relationship between the structures of the polymers and secondary ions. The influence of fluorocarbon segment length on the formation of secondary ions in a ToF‐SIMS process was studied. The characteristic negative and positive ions were found to be related to the chemical structure of the repeat units of the polymers. The ToF‐SIMS results provided some useful information on the fragmentation mechanism of positive and negative secondary ions. The results indicate that recombination of the ions in the gas phase is unlikely in a static SIMS process. Copyright © 2002 John Wiley & Sons, Ltd.
Ammonia adsorption on Zr(0001): effect of electron bombardment on hydrogen production
Authors: Stojilovic N. , Kang Y. C. , Ramsier R. D.
Published: November 2002

With the ultimate goal of modifying the surface chemistry of zirconium, we present a temperature‐programmed desorption (TPD) study of ammonia adsorbed on Zr(0001) followed by soft electron bombardment. The TPD data indicate that water accompanies the thermal desorption of ammonia near 730 K, which is a result of the mixing of oxygen atoms from the subsurface region with ammonia dissociation products. Nitrogen is left at the surface following TPD and can be removed only by repeated sputtering cycles. These thermal effects occur with or without electronic excitation. Electron bombardment does, however, result in the desorption of hydrogen gas in TPD near 310 K, indicating the formation of new hydrogenic species at the surface via electronic excitation. The electron‐induced cross‐sections for the production of these species are determined to be in the 1–5(×10−18) cm2 range. Copyright © 2002 John Wiley & Sons, Ltd.
THE DOMESTICATION OF THE MALE? RECENT RESEARCH ON NINETEENTH- AND TWENTIETH-CENTURY BRITISH MASCULINITY
Authors: FRANCIS MARTIN
Published: November 2002

This review will survey some of the most important historical studies of nineteenth- and twentieth-century British masculinity which have appeared in the last decade. It endorses John Tosh's insistence that it is necessary to move beyond the homosocial environments and explicit ideologies of ‘manliness’ studied by those historians who, in the 1980s, first sought a gendered history of men in modern Britain. However, it also warns that a commendable desire to ensure that men's identities are located in relationship to women, children, and the home must be accompanied by a degree of scepticism towards unproblematic narratives of male domestication. Men constantly travelled back and forth across the frontier of domesticity, if only in the realm of imagination, attracted by the responsibilities of marriage and fatherhood, but also enchanted by various escapist fantasies (especially the adventure story or war film) which celebrated militaristic hypermasculinity and male bonding. This commentary also insists that, in order to enrich our understanding of male domesticity, existing studies of middle-class men will have to be supplemented by further research on aristocratic and working-class masculinities, and that national, ethnic, and racial differences also need to be more fully registered.
“Our Chronic and Desperate Situation”: Anthracite Communities and the Emergence of Redevelopment Policy in Pennsylvania and the United States, 1945–1965
Authors: Wilson Gregory
Published: November 2002

On 3 May 1954, Lehigh Coal and Navigation Company announced that it would close its anthracite mining operations in Pennsylvania's Panther Valley. Company officials had hoped to keep some mines open but net losses in 1953 amounted to $1.4 million and the trend continued into early 1954. The company stated they would reopen the mines only if miners would work harder and produce more. All area locals of the United Mine Workers of America (UMW) voted to accept the program except one, Tamaqua Local 1571. Arguing that the new rules violated existing wage agreements, workers from this Local picketed the mines and called on miners across the anthracite region to join them. Tamaqua miners offered an alternative plan that called for workers to share control over management and production decisions. Lehigh managers refused and closed the mines, effective from 30 June. As other mining companies began to collapse in the 1950s and 1960s, local workers, business owners, union leaders, and politicians made efforts to either open mines or attract new industries. However, unemployment remained a difficult problem for the Panther Valley and for the entire anthracite region and the area still exhibits higher than average unemployment.
Solitons and oscillitons in cold bi-ion
plasmas: a parameter study
Authors: DUBININ E. , SAUER K. , McKENZIE J. F.
Published: November 2002

We investigate the structure of nonlinear stationary waves propagating
obliquely to the magnetic field in a cold bi-ion plasma. By using the constants of
motion that follow from the multi fluid equations, the system may be described by four
coupled first-order differential equations. A new constant of motion characterizing
a bi-ion flow (called the ‘energy difference integral’) is found. The combination
of relations between the flow speeds derived from the conservation laws, which
we call the ‘momentum–energy hodographs’, reveal some important features of
stationary waves and solitons. Soliton solutions representing both compressions
and rarefactions in the ion fluids exist in specific windows in the ‘Alfvén Mach
number–obliquity’ space. In other windows, solutions characterized by both
oscillating and soliton properties (‘oscillitons’) exist. Critical Mach numbers and
propagation angles narrow the size of the windows where smooth soliton solutions can
be constructed.
Asymmetric self-focusing of a laser pulse in
plasma
Authors: UPADHYAY A. , TRIPATHI V. K. , SHARMA A. K. , PANT H. C.
Published: November 2002

An intense short-pulse laser propagating through a plasma undergoes
self-pulse distortion due to the combined effects of nonlinearity-induced self-focusing
and dispersion. The nonlinearity arises as a result of relativistic mass
variation. The low-intensity front of the pulse converges mildly, while the high-intensity
later portions self-focus strongly. However, at the intensity maxima, the
self-focusing effect is masked by the saturation effect of the nonlinear refractive
index. The group velocity is also a function of intensity; as a result, the front of
the pulse becomes sharpened, while the tail tends to be broadened.
EPIBIOTIC SPONGES ON THE SCALLOPS CHLAMYS HASTATA AND CHLAMYS RUBIDA: INCREASED SURVIVAL IN A HIGH-SEDIMENT ENVIRONMENT
Authors: Burns Duncan O. , Bingham Brian L.
Published: November 2002

The small free-swimming scallops, Chlamys hastata and Chlamys rubida, are frequently encrusted by the sponges Mycale adhaerens and Myxilla incrustans. It is unclear why this association exists. We hypothesized that living on scallop valves increases sponge survival by reducing the effects of sediment accumulation. Scallops were collected to measure correlations between sediment load and encrusting sponge mass. In the laboratory, the survival of sponges on living scallops and empty scallop valves was measured. Time-lapse video was used to quantify spontaneous swimming and clapping of C. hastata. In the field, both scallop size and sponge mass were significantly greater in high turbidity sites. In the laboratory, sponges on empty scallop valves experienced near complete mortality after five weeks. Manually clearing sediments increased survival but did not duplicate the high survival of sponges on living scallops, which regularly swam or clapped their valves.
Systematic position and reproduction of squid of the genus Alloteuthis (Cephalopoda: Loliginidae) in the eastern Mediterranean
Authors: Laptikhovsky Vladimir , Salman Alp , Önsoy Bahadir , Katağan Tuncer
Published: November 2002

Squid of the genus Alloteuthis from the Aegean Sea and eastern Mediterranean were identified as A. media. It is not possible to distinguish A. media from A. subulata by relative fin length. Both ‘species’ are probably intraspecific forms. Egg size varied from 1·5 to 2·3 mm. Oocyte maturation in the ovary occurs in batches. The potential fecundity is some 1000–4000 eggs, most of these being released during continuous spawning accompanied by female growth.
Study of the first reported nest of loggerhead sea turtle, Caretta caretta, in the Spanish Mediterranean coast
Authors: Tomás J. , Mons J.L. , Martín J.J. , Bellido J.J. , Castillo J.J.
Published: November 2002

We summarize all the data of nest placement, incubation period, emergence of hatchlings and nest study of the first reported nesting event of a loggerhead turtle Caretta caretta (Reptilia: Cheloniidae) in the Spanish Mediterranean coast. The nest was laid in a beach of Almería province (south-east Spain) in July 2001. The incubation period was 58 days. Forty-two hatchlings emerged from a total of 97 eggs laid. Future beach surveys will determine whether this is a sporadic nesting event or whether loggerheads nest frequently in these coasts.
Breeding period of the arrow crab Stenorhynchus seticornis from Couves Island, south-eastern Brazilian coast
Authors: Cobo Valter José
Published: November 2002

This study focused on the breeding period of Stenorhynchus seticornis (Brachyura, Majidae, Inachinae) in the south-eastern Brazilian coast. Monthly collections were accomplished from January to December of 2000. A catch effort of approximately 4 h was allocated to each monthly survey. The breeding intensity was determined as the percentage of ovigerous crabs within the whole adult female population. A total of 204 adult females were obtained, from which 74·5% presented eggs attached to their pleopods. Ovigerous females were observed year-round, usually comprising more than 60% of sampled adult females. The ovigerous frequency was not found to be correlated with either temperature or salinity.
Novel insights into green sea turtle behaviour using animal-borne video cameras
Authors: Heithaus Michael R. , McLash Justin J. , Frid Alejandro , Dill Lawrence M. , Marshall Greg J.
Published: November 2002

An animal-borne video camera and data-logger was used to collect behavioural data on green (Chelonia mydas) and loggerhead (Caretta caretta) turtles in Western Australia. This technique provided novel insights into the behaviour of green turtles including an apparent self-cleaning behaviour. Also, ctenophores and jellyfish might be more important in the diet of these turtles than previously thought.
Time and time again: two volumes by William Lane Craig William Lane Craig The Tensed Theory of Time: A Critical Examination. Synthese Library Volume 293. (Dordrecht: Kluwer Academic Publishers, 2000). Pp. v+287. £78.00 (Hbk). ISBN 0792366344. William Lane Craig The Tenseless Theory of Time: A Critical Examination. Synthese Library Volume 294. (Dordrecht: Kluwer Academic Publishers, 2000). Pp. v+256. £65.00 (Hbk). ISBN 0792366352.
Authors: HELM PAUL
Published: November 2002

The two books make a notable contribution in drawing together many of the philosophical problems about time, and the associated literature. The expositions are also valuable for their interdisciplinary strengths, especially in the history and philosophy of science and (to a lesser extent) in theology, and for the clarity and thoroughness of Craig's approach. However, the two books do not present, as might at first appear, a side by side exposition of the respective strengths and weaknesses of the A-series and the B-series views of time. They are, rather, one interconnected defence of the A-series view. Some of the strengths and weaknesses of Craig's exposition and defence of the A-series view are noted.
The Politics of Sex Education Policy in England and Wales
and The Netherlands since the 1980s
Authors: LEWIS JANE , KNIJN TRUDIE
Published: November 2002

Teenage pregnancy rates are extremely high in the UK and extremely low
in The Netherlands. Sex education is acknowledged to be a determining
factor. While it is by no means the most important factor, it provides a
useful comparative lens through which to examine the very different
approaches of the British and Dutch to policy-making in this sensitive
area.

The issue of sex education is controversial in both the UK and The
Netherlands, but while the political debate has been fierce in the UK it has
been largely absent in The Netherlands. Our research used documentary
sources and interviews to investigate the recent history of policy-making
on sex education at the central government level; compared a selection of
key texts used in secondary schools; and drew on exploratory fieldwork in
three English and three Dutch secondary schools. We find that the
approach to the issue is in large part determined by the struggle over
ideas in respect of the wider issues of change in the family and sexuality.
We suggest that the adversarial nature of the politics of sex education in
England and Wales results in a message that lacks coherence, which is in
turn reflected in what happens in the classroom. We do not advocate any
simple attempt at ‘policy borrowing’, but rather highlight the importance
of understanding the differences in the nature and conduct of the debate.
Part of the Problem or Part of the Solution?
Social Housing Allocation Policies and Social Exclusion in
Britain
Authors: PAWSON HAL , KINTREA KEITH
Published: November 2002

This article examines claims that social housing allocations policies can,
on the one hand, contribute to and on the other, counter, social exclusion.
In setting the scene, the paper investigates connections between
housing processes and social exclusion and describes the development of
social housing allocations systems over the past few decades. Drawing on
evidence from two recently completed national studies in England and
Scotland it shows that allocation policies contribute to social exclusion in
three main ways. First, a large proportion of social landlords restrict eligibility
for social housing thereby contributing directly to exclusion.
Second, mechanisms within allocation systems continue to segregate the
most excluded to the worst residential areas. Third, through the 1990s
allocation policies became increasingly coercive, so reducing or eliminating
tenant choice over their own housing in distinct contrast to the
choice that is available in the private market. The paper then reviews the
dilemmas faced by policy-makers: whilst aspects of allocations contribute
to social exclusion at the individual level, they may be justified by their
role in promoting sustainable residential communities. Although there
are hopes that the ‘choice-based’ approaches to lettings which emerged
in the late 1990s can both boost community sustainability and counter
the disabling impact of coercive approaches, the article suggests it is
unlikely that such methods can significantly enhance social inclusion as
long as social housing remains a housing sector of last resort, with in-built
disadvantages.
Reports and Surveys
Authors: Rudall B. H.
Published: November 2002

I. AUTOMATION REPORTS

I.1. UK Manufacturers Buy Largest Number of Robots Since Records Began in 1978

Latest research figures from the University of Warwick (UK) show that UK manufacturers installed a record breaking 1,941 robots in 2001 – the largest number of new robots ever installed in the UK in any one year since records began in 1978.
Multifunctional walking quadruped
Authors: Zielinska T. , Heng John
Published: November 2002

A multifunctional 4 legged walking machine that is being developed in the Robotics Research Centre (NTU) is described. The major factors influencing the design requirements include minimisation of the weight of
the machine and maximisation of workspace of the legs. The designed walking machine can adopt a variety of configurations, such as insect, mammalian, reptile or human. The device is invertable (i.e. can turn over). It can use its legs as manipulators, hence it can perform basic pick-and-place functions. A control system was built using the QNX real-time operating system platform. The software was designed using the client-server approach.
Congress Report
Authors: Erbe Heinz-H.
Published: November 2002

15th TRIENNIAL WORLD CONGRESS OF THE INTERNATIONAL FEDERATION
OF AUTOMATIC CONTROL (IFAC), BARCELONA, SPAIN, 21st–26th JULY, 2002

The World Congress under the Spanish presidency (Prof. P. Albertos) brought together about 2000 researchers and practitioners of control theory, technology and applications. The famous Gran Teatro del Liceo of Barcelona was
the right location for the opening ceremony, whereas the congress sessions were held at the campus of the Universidad Politecnica de Catalunia.
An Improved Upper Bound
for the Hexagonal Lattice Site
Percolation Critical Probability
Authors: WIERMAN JOHN C.
Published: November 2002

The hexagonal lattice site percolation critical probability is shown to be at most 0.79472,
improving the best previous mathematically rigorous upper bound. The bound is derived
by using the substitution method to compare the site model with the bond model, the latter
of which is exactly solved. Shortcuts which eliminate a substantial amount of computation
make the derivation of the bound possible.
Two Short Proofs Concerning Tree-Decompositions
Authors: BELLENBAUM PATRICK , DIESTEL REINHARD
Published: November 2002

We give short proofs of the following two results: Thomas's theorem that every finite graph
has a linked tree-decomposition of width no greater than its tree-width; and the ‘tree-width
duality theorem’ of Seymour and Thomas, that the tree-width of a finite graph is exactly
one less than the largest order of its brambles.
Chemical chaperones increase the cellular activity of N370S β-glucosidase: A therapeutic strategy for Gaucher disease
Authors: Sawkar Anu R. , Cheng Wei-Chieh , Beutler Ernest , Wong Chi-Huey , Balch William E. , Kelly Jeffery W.
Published: November 2002

Gaucher disease is a lysosomal storage disorder caused by deficient lysosomal β-glucosidase (β-Glu) activity. A marked decrease in enzyme activity results in progressive accumulation of the substrate (glucosylceramide) in macrophages, leading to hepatosplenomegaly, anemia, skeletal lesions, and sometimes CNS involvement. Enzyme replacement therapy for Gaucher disease is costly and relatively ineffective for CNS involvement. Chemical chaperones have been shown to stabilize various proteins against misfolding, increasing proper trafficking from the endoplasmic reticulum. We report herein that the addition of subinhibitory concentrations (10 μM) of
N
-(
n
-nonyl)deoxynojirimycin (NN-DNJ) to a fibroblast culture medium for 9 days leads to a 2-fold increase in the activity of N370S β-Glu, the most common mutation causing Gaucher disease. Moreover, the increased activity persists for at least 6 days after the withdrawal of the putative chaperone. The NN-DNJ chaperone also increases WT β-Glu activity, but not that of L444P, a less prevalent Gaucher disease variant. Incubation of isolated soluble WT enzyme with NN-DNJ reveals that β-Glu is stabilized against heat denaturation in a dose-dependent fashion. We propose that NN-DNJ chaperones β-Glu folding at neutral pH, thus allowing the stabilized enzyme to transit from the endoplasmic reticulum to the Golgi, enabling proper trafficking to the lysosome. Clinical data suggest that a modest increase in β-Glu activity may be sufficient to achieve a therapeutic effect.
Quantifying predictability in a model with statistical features of the atmosphere
Authors: Kleeman Richard , Majda Andrew J. , Timofeyev Ilya
Published: November 2002

The Galerkin truncated inviscid Burgers equation has recently been shown by the authors to be a simple model with many degrees of freedom, with many statistical properties similar to those occurring in dynamical systems relevant to the atmosphere. These properties include long time-correlated, large-scale modes of low frequency variability and short time-correlated “weather modes” at smaller scales. The correlation scaling in the model extends over several decades and may be explained by a simple theory. Here a thorough analysis of the nature of predictability in the idealized system is developed by using a theoretical framework developed by R.K. This analysis is based on a relative entropy functional that has been shown elsewhere by one of the authors to measure the utility of statistical predictions precisely. The analysis is facilitated by the fact that most relevant probability distributions are approximately Gaussian if the initial conditions are assumed to be so. Rather surprisingly this holds for both the equilibrium (climatological) and nonequilibrium (prediction) distributions. We find that in most cases the absolute difference in the first moments of these two distributions (the “signal” component) is the main determinant of predictive utility variations. Contrary to conventional belief in the ensemble prediction area, the dispersion of prediction ensembles is generally of secondary importance in accounting for variations in utility associated with different initial conditions. This conclusion has potentially important implications for practical weather prediction, where traditionally most attention has focused on dispersion and its variability.
Peroxone chemistry: Formation of H
2
O
3
and ring-(HO
2
)(HO
3
) from O
3
/H
2
O
2
Authors: Xu Xin , Goddard William A.
Published: November 2002

The recent observation [Wentworth, P., Jones, L. H., Wentworth, A. D., Zhu, X. Y., Larsen, N. A., Wilson, I. A., Xu, X., Goddard, W. A., Janda, K. D., Eschenmoser, A. & Lerner, R. A. (2001)
Science
293, 1806–1811] that antibodies form H
2
O
2
from
1
O
2
plus H
2
O was explained in terms of the formation of the H
2
O
3
species that in the antibody reacts with a second H
2
O
3
to form H
2
O
2
. There have been few reports of the chemistry for forming H
2
O
3
, but recently Engdahl and Nelander [Engdahl, A. & Nelander, B. (2002)
Science
295, 482–483] reported that photolysis of the ozone–hydrogen peroxide complex in argon matrices leads to significant concentrations of H
2
O
3
. We report here the chemical mechanism for this process, determined by using first-principles quantum mechanics. We show that in an argon matrix it is favorable (3.5 kcal/mol barrier) for H
2
O
2
and O
3
to form a [(HO
2
)(HO
3
)] hydrogen-bonded complex [head-to-tail seven-membered ring (7r)]. In this complex, the barrier for forming H
2
O
3
plus
3
O
2
is only 4.8 kcal/mol, which should be observable by means of thermal processes (not yet reported). Irradiation of the [(HO
2
)(HO
3
)-7r] complex should break the HO–OO bond of the HO
3
moiety, eliminating
3
O
2
and leading to [(HO
2
)(HO)]. This [(HO
2
)(HO)] confined in the matrix cage is expected to rearrange to also form H
2
O
3
(observed experimentally). We show that these two processes can be distinguished isotopically. These results (including the predicted vibrational frequencies) suggest strategies for synthesizing H
2
O
3
and characterizing its chemistry. We suggest that the [(HO
2
)(HO
3
)-7r] complex and H
2
O
3
are involved in biological, atmospheric, and environmental oxidative processes.
Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells
Authors: Stappenbeck Thaddeus S. , Hooper Lora V. , Gordon Jeffrey I.
Published: November 2002

The adult mouse intestine contains an intricate vascular network. The factors that control development of this network are poorly understood. Quantitative three-dimensional imaging studies revealed that a plexus of branched interconnected vessels developed in small intestinal villi during the period of postnatal development that coincides with assembly of a complex society of indigenous gut microorganisms (microbiota). To investigate the impact of this environmental transition on vascular development, we compared the capillary networks of germ-free mice with those of ex-germ-free animals colonized during or after completion of postnatal gut development. Adult germ-free mice had arrested capillary network formation. The developmental program can be restarted and completed within 10 days after colonization with a complete microbiota harvested from conventionally raised mice, or with
Bacteroides thetaiotaomicron
, a prominent inhabitant of the normal mouse/human gut. Paneth cells in the intestinal epithelium secrete antibacterial peptides that affect luminal microbial ecology. Comparisons of germ-free and
B. thetaiotaomicron
-colonized transgenic mice lacking Paneth cells established that microbial regulation of angiogenesis depends on this lineage. These findings reveal a previously unappreciated mechanism of postnatal animal development, where microbes colonizing a mucosal surface are assigned responsibility for regulating elaboration of the underlying microvasculature by signaling through a bacteria-sensing epithelial cell.
Control of biochemical reactions through supramolecular RING domain self-assembly
Authors: Kentsis Alex , Gordon Ronald E. , Borden Katherine L. B.
Published: November 2002

RING domains act in a variety of unrelated biochemical reactions, with many of these domains forming key parts of supramolecular assemblies in cells. Here, we observe that purified RINGs from a variety of functionally unrelated proteins, including promyelocytic leukemia protein, KAP-1/TIF1β, Z, Mel18, breast cancer susceptibility gene product 1 (BRCA1), and BRCA1-associated RING domain (BARD1), self-assemble into supramolecular structures
in vitro
that resemble those they form in cells. RING bodies form polyvalent binding surfaces and scaffold multiple partner proteins. Separation of RING bodies from monomers reveals that self-assembly controls and amplifies their specific activities in two unrelated biochemistries: reduction of 5′ mRNA cap affinity of eIF4E by promyelocytic leukemia protein and Z, and E3 ubiquitin conjugation activity of BARD1:BRCA1. Functional significance of self-assembly is underscored by partial restoration of assembly and E3 activity of cancer predisposing BRCA1 mutant by forced oligomerization. RING self-assembly creates bodies that act structurally as polyvalent scaffolds, thermodynamically by amplifying activities of partner proteins, and catalytically by spatiotemporal coupling of enzymatic reactions. These studies reveal a general paradigm of how supramolecular structures may function in cells.
On the global Cauchy problem for the nonlinear Schrödinger equation
Authors: Bourgain Jean
Published: November 2002

We mainly survey recent results on the nonlinear
Schrödinger equations with special emphasis on the Cauchy
problem, local and global in time and for various regularity
assumptions on the initial data.
Some nonlinear elliptic equations from geometry
Authors: Li YanYan
Published: November 2002

We describe some recent work on certain nonlinear elliptic equations from geometry. These include the problem of prescribing scalar curvature on 𝕊

n

, the Yamabe problem on manifolds with boundary, and the best Sobolev inequality on Riemannian manifolds.
The analysis of the intramacrophagic virulome ofBrucella suisdeciphers the environment encountered by the pathogen inside the macrophage host cell
Authors: Köhler Stephan , Foulongne Vincent , Ouahrani-Bettache Safia , Bourg Gisèle , Teyssier Jacques , Ramuz Michel , Liautard Jean-Pierre
Published: November 2002

The pathogenBrucella suisresides and multiplies within a phagocytic vacuole of its host cell, the macrophage. The resulting complex relationship has been investigated by the analysis of the set of genes required for virulence, which we call intramacrophagic virulome. Ten thousand two hundred and seventy-two miniTn5 mutants ofB. suisconstitutively expressinggfpwere screened by fluorescence microscopy for lack of intracellular multiplication in human macrophages. One hundred thirty-one such mutants affected in 59 different genes could be isolated, and a function was ascribed to 53 of them. We identified genes involved in (i) global adaptation to the intracellular environment, (ii) amino acid, and (iii) nucleotide synthesis, (iv) sugar metabolism, (v) oxidoreduction, (vi) nitrogen metabolism, (vii) regulation, (viii) disulphide bond formation, and (ix) lipopolysaccharide biosynthesis. Results led to the conclusion that the replicative compartment ofB. suisis poor in nutrients and characterized by low oxygen tension, and that nitrate may be used for anaerobic respiration. Intramacrophagic virulome analysis hence allowed the description of the nature of the replicative vacuole of the pathogen in the macrophage and extended our understanding of the niche in whichB. suisresides. We propose calling this specific compartment “brucellosome.”
Visualization by comprehensive microarray analysis of gene expression programs during transdifferentiation of mesophyll cells into xylem cells
Authors: Demura Taku , Tashiro Gen , Horiguchi Gorou , Kishimoto Naoki , Kubo Minoru , Matsuoka Naoko , Minami Atsushi , Nagata-Hiwatashi Miyo , Nakamura Keiko , Okamura Yoshimichi , Sassa Naomi , Suzuki Shinsuke , Yazaki Junshi , Kikuchi Shoshi , Fukuda Hiroo
Published: November 2002

Plants have a unique transdifferentiation mechanism by which differentiated cells can initiate a new program of differentiation. We used a comprehensive analysis of gene expression in an
in vitro
zinnia (
Zinnia elegans
L.) culture model system to gather fundamental information about the gene regulation underlying the transdifferentiation of plant cells. In this model, photosynthetic mesophyll cells isolated from zinnia leaves transdifferentiate into xylem cells in a morphogenic process characterized by features such as secondary-wall formation and programmed cell death. More than 8,000 zinnia cDNA clones were isolated from an equalized cDNA library prepared from cultured cells transdifferentiating into xylem cells. Microarray analysis using these cDNAs revealed several types of unique gene regulation patterns, including: the transient expression of a set of genes during cell isolation, presumably induced by wounding; a rapid reduction in the expression of photosynthetic genes and the rapid induction of protein synthesis-associated genes during the first stage; the preferential induction of auxin-related genes during the subsequent stage; and the transient induction of genes closely associated with particular morphogenetic events, including cell-wall formation and degradation and programmed cell death during the final stage. This analysis also revealed a number of previously uncharacterized genes encoding proteins that function in signal transduction, such as protein kinases and transcription factors that are expressed in a stage-specific manner. These findings provide new clues to the molecular mechanisms of both plant transdifferentiation and wood formation.
Bornyl diphosphate synthase: Structure and strategy for carbocation manipulation by a terpenoid cyclase
Authors: Whittington Douglas A. , Wise Mitchell L. , Urbansky Marek , Coates Robert M. , Croteau Rodney B. , Christianson David W.
Published: November 2002

The x-ray crystal structure of dimeric (+)-bornyl diphosphate synthase, a metal-requiring monoterpene cyclase from
Salvia officinalis
, is reported at 2.0-Å resolution. Each monomer contains two α-helical domains: the C-terminal domain catalyzes the cyclization of geranyl diphosphate, orienting and stabilizing multiple reactive carbocation intermediates; the N-terminal domain has no clearly defined function, although its N terminus caps the active site in the C-terminal domain during catalysis. Structures of complexes with aza analogues of substrate and carbocation intermediates, as well as complexes with pyrophosphate and bornyl diphosphate, provide “snapshots” of the terpene cyclization cascade.
Circular dichroism spectra of short, fixed-nucleus alanine helices
Authors: Chin Der-Hang , Woody Robert W. , Rohl Carol A. , Baldwin Robert L.
Published: November 2002

Very short alanine peptide helices can be studied in a fixed-nucleus, helix-forming system [Siedlicka, M., Goch, G., Ejchart, A., Sticht, H. & Bierzynski, A. (1999)
Proc. Natl. Acad. Sci. USA
96, 903–908]. In a 12-residue sequence taken from an EF-hand protein, the four C-terminal peptide units become helical when the peptide binds La
3+
, and somewhat longer helices may be made by adding alanine residues at the C terminus. The helices studied here contain 4, 8, or 11 peptide units. Surprisingly, these short fixed-nucleus helices remain almost fully helical from 4 to 65°C, according to circular dichroism results reported here, and in agreement with titration calorimetry results reported recently. These peptides are used here to define the circular dichroism properties of short helices, which are needed for accurate measurement of helix propensities. Two striking properties are: (
i
) the temperature coefficient of mean peptide ellipticity depends strongly on helix length; and (
ii
) the intensity of the signal decreases much less rapidly with helix length, for very short helices, than supposed in the past. The circular dichroism spectra of the short helices are compared with new theoretical calculations, based on the experimentally determined direction of the NV
1
transition moment.
Cell surface CCR5 density determines the postentry efficiency of R5 HIV-1 infection
Authors: Lin Yea-Lih , Mettling Clément , Portales Pierre , Reynes Jacques , Clot Jacques , Corbeau Pierre
Published: November 2002

We have recently reported that the mean number of CCR5 coreceptors at the surface of CD4+T cells (CCR5 density) correlates with viral load and disease progression in HIV-1-infected persons. Here, we definitively establish that CCR5 density determines the level of virus production and identify the stages of HIV-1 replicative cycle modulated by this effect. We show, by transducing theCCR5gene into CCR5+cells, that CCR5 overexpression resulted in an HIV-1 overinfectability. We sorted HOS-CD4+-CCR5+cells into two subpopulations, HOShighand HOSlow, the former expressing seven times more cell surface CCR5 molecules than the latter. Virus production was 30–80 times higher in HOShighcells than in HOSlowcells after a single round of infection. In contrast, only twice as many viral particles entered the cytosol of HOShighcells as compared with the cytosol of HOSlowcells. Yet, seven times as many early, and 24 times as many late, reverse transcription products were found in HOShighcells as compared with HOSlowcells. Moreover, a 24- to 30-fold difference in the number of copies of integrated HIV-1 DNA was observed. No difference in HIV-1 LTR activation between the two cell lines was evident. Finally, we show that the higher virus production observed in HOShighcells is inhibited by pertussis toxin, a Gαi protein inhibitor. Thus, CCR5 density mainly modulates postentry steps of the virus life cycle, particularly the reverse transcription. These data explain why CCR5 density influences HIV-1 disease progression and underline the therapeutic interest of lowering CCR5 expression.
The mechanism of topoisomerase I poisoning by a camptothecin analog
Authors: Staker Bart L. , Hjerrild Kathryn , Feese Michael D. , Behnke Craig A. , Burgin Alex B. , Stewart Lance
Published: November 2002

We report the x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan. Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, Topotecan acts as an uncompetitive inhibitor. The structure can explain several of the known structure–activity relationships of the camptothecin family of anticancer drugs and suggests that there are at least two classes of mutations that can produce a drug-resistant enzyme. The first class includes changes to residues that contribute to direct interactions with the drug, whereas a second class would alter interactions with the DNA and thereby destabilize the drug-binding site.
Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation
Authors: Qin Mei , Kang Julia , Smith Carolyn Beebe
Published: November 2002

In humans, failure to express the fragile X mental retardation protein (FMRP) gives rise to fragile X syndrome, the most common form of inherited mental retardation. A fragile X knockout (
fmr1
KO) mouse has been described that has some of the characteristics of patients with fragile X syndrome, including immature dendritic spines and subtle behavioral deficits. In our behavioral studies,
fmr1
KO mice exhibited hyperactivity and a higher rate of entrance into the center of an open field compared with controls, suggesting decreased levels of anxiety. Our finding of impaired performance of
fmr1
KO mice on a passive avoidance task is suggestive of a deficit in learning and memory. In an effort to understand what brain regions are involved in the behavioral abnormalities, we applied the [
14
C]deoxyglucose method for the determination of cerebral metabolic rates for glucose (CMR
glc
). We measured CMR
glc
in 38 regions in adult male
fmr1
KO and WT littermates. We found CMR
glc
was higher in all 38 regions in
fmr1
KO mice, and in 26 of the regions, differences were statistically significant. Differences in CMR
glc
ranged from 12% to 46%, and the greatest differences occurred in regions of the limbic system and primary sensory and posterior parietal cortical areas. Regions most affected are consistent with behavioral deficiencies and regions in which FMRP expression is highest. Higher CMR
glc
in fragile X mice may be a function of abnormalities found in dendritic spines.
The single, ancient origin of chromist plastids
Authors: Yoon Hwan Su , Hackett Jeremiah D. , Pinto Gabriele , Bhattacharya Debashish
Published: November 2002

Algae include a diverse array of photosynthetic eukaryotes excluding land plants. Explaining the origin of algal plastids continues to be a major challenge in evolutionary biology. Current knowledge suggests that plastid primary endosymbiosis, in which a single-celled protist engulfs and “enslaves” a cyanobacterium, likely occurred once and resulted in the primordial alga. This eukaryote then gave rise through vertical evolution to the red, green, and glaucophyte algae. However, some modern algal lineages have a more complicated evolutionary history involving a secondary endosymbiotic event, in which a protist engulfed an existing eukaryotic alga (rather than a cyanobacterium), which was then reduced to a secondary plastid. Secondary endosymbiosis explains the majority of algal biodiversity, yet the number and timing of these events is unresolved. Here we analyzed a five-gene plastid data set to show that a taxonomically diverse group of chlorophyll

c
2

-containing protists comprising cryptophyte, haptophyte, and stramenopiles algae (Chromista) share a common plastid that most likely arose from a single, ancient (≈1,260 million years ago) secondary endosymbiosis involving a red alga. This finding is consistent with Chromista monophyly and implicates secondary endosymbiosis as an important force in generating eukaryotic biodiversity.
Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy
Authors: Vlassara Helen , Cai Weijing , Crandall Jill , Goldberg Teresia , Oberstein Robert , Dardaine Veronique , Peppa Melpomeni , Rayfield Elliot J.
Published: November 2002

Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (
P
= 0.02) and on L-AGE decreased by 30% (
P
= 0.02). The mononuclear cell tumor necrosis factor-α/β-actin mRNA ratio was 1.4 ± 0.5 on H-AGE and 0.9 ± 0.5 on L-AGE (
P
= 0.05), whereas serum vascular adhesion molecule-1 was 1,108 ± 429 and 698 ± 347 ng/ml (
P
= 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-α rose by 86.3% (
P
= 0.006) and declined by 20% (
P
, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (
P
= 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (
P
< 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (
P
= 0.06) and reduced by 40% on L-AGE (
P
= 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (
P
< 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.
Are helionitronium trications stable?
Authors: Eisfeld Wolfgang , Francisco Joseph S.
Published: November 2002

In a recent article [Olah, G. A., Prakash, G. K. S. & Rasul, G. (1999)
Proc. Natl. Acad. Sci. USA
96, 3494–3495] the authors found that the helionitronium trication, HeNO

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, is an unusually stable helium-containing polyatomic ion. This result was based on second-order many-body perturbation (MP2) calculations that showed that strong binding should occur between the oxygen and helium atoms in the assumed singlet ground state. The dissociation energy with respect to NO
+
and HeO
2+
was predicted to be 7.95 eV. We show here by thorough multireference configuration interaction (MRCI) studies that the ground state for the helionitronium trication is a triplet
3
B
1
state with He binding to the N atom (
C

2
v

). The He—O bound structure of
C
s
symmetry is not stable. Dissociation of the helionitronium trication occurs toward NO

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and He
+
, and the trication is bound by at most 0.25 eV. These results indicate that the helionitronium trication is unstable under ambient conditions. The discrepancies between our results and the previous study are explained by the strong multireference character of the wave function of the trication.
Microarray-based detection and genotyping of viral pathogens
Authors: Wang David , Coscoy Laurent , Zylberberg Maxine , Avila Pedro C. , Boushey Homer A. , Ganem Don , DeRisi Joseph L.
Published: November 2002

The detection of viral pathogens is of critical importance in biology, medicine, and agriculture. Unfortunately, existing techniques to screen for a broad spectrum of viruses suffer from severe limitations. To facilitate the comprehensive and unbiased analysis of viral prevalence in a given biological setting, we have developed a genomic strategy for highly parallel viral screening. The cornerstone of this approach is a long oligonucleotide (70-mer) DNA microarray capable of simultaneously detecting hundreds of viruses. Using virally infected cell cultures, we were able to efficiently detect and identify many diverse viruses. Related viral serotypes could be distinguished by the unique pattern of hybridization generated by each virus. Furthermore, by selecting microarray elements derived from highly conserved regions within viral families, individual viruses that were not explicitly represented on the microarray were still detected, raising the possibility that this approach could be used for virus discovery. Finally, by using a random PCR amplification strategy in conjunction with the microarray, we were able to detect multiple viruses in human respiratory specimens without the use of sequence-specific or degenerate primers. This method is versatile and greatly expands the spectrum of detectable viruses in a single assay while simultaneously providing the capability to discriminate among viral subtypes.
Multiple subnuclear targeting signals of the leukemia-related AML1/ETO and ETO repressor proteins
Authors: Barseguian Karina , Lutterbach Bart , Hiebert Scott W. , Nickerson Jeffrey , Lian Jane B. , Stein Janet L. , van Wijnen Andre J. , Stein Gary S.
Published: November 2002

Leukemic disease can be linked to aberrant gene expression. This often is the result of molecular alterations in transcription factors that lead to their misrouting within the nucleus. The acute myelogenous leukemia-related fusion protein AML1/ETO is a striking example. It originates from a gene rearrangement t(8;21) that fuses the N-terminal part of the key hematopoietic regulatory factor AML1 (RUNX1) to the ETO (MTG8) repressor protein. AML1/ETO lacks the intranuclear targeting signal of the wild-type AML1 and is directed by the ETO component to alternate nuclear matrix-associated sites. To understand this aberrant subnuclear trafficking of AML1/ETO, we created a series of mutations in the ETO protein. These were characterized biochemically by immunoblotting and
in situ
by immunofluorescence microscopy. We identified two independent subnuclear targeting signals in the N- and C-terminal regions of ETO that together direct ETO to the same binding sites occupied by AML1/ETO. However, each segment alone is targeted to a different intranuclear location. The N-terminal segment contains a nuclear localization signal and the conserved hydrophobic heptad repeat domain responsible for protein dimerization and interaction with the mSin3A transcriptional repressor. The C-terminal segment spans the nervy domain and the zinc finger region, which together support interactions with the corepressors N-CoR and HDACs. Our findings provide a molecular basis for aberrant subnuclear targeting of the AML1/ETO protein, which is a principal defect in t(8;21)-related acute myelogenous leukemia.