bluuebunny/crossref_metadata_2025 huggingface dataset:
Nature's style: Naturally trendy
Authors: Cohn Timothy A. , Lins Harry F.
Published: December 2005

Hydroclimatological time series often exhibit trends. While trend magnitude can be determined with little ambiguity, the corresponding statistical significance, sometimes cited to bolster scientific and political argument, is less certain because significance depends critically on the null hypothesis which in turn reflects subjective notions about what one expects to see. We consider statistical trend tests of hydroclimatological data in the presence of long‐term persistence (LTP). Monte Carlo experiments employing FARIMA models indicate that trend tests which fail to consider LTP greatly overstate the statistical significance of observed trends when LTP is present. A new test is presented that avoids this problem. From a practical standpoint, however, it may be preferable to acknowledge that the concept of statistical significance is meaningless when discussing poorly understood systems.
Climate effects of global land cover change
Authors: Gibbard S. , Caldeira K. , Bala G. , Phillips T. J. , Wickett M.
Published: December 2005

When changing from grass and croplands to forest, there are two competing effects of land cover change on climate: an albedo effect which leads to warming and an evapotranspiration effect which tends to produce cooling. It is not clear which effect would dominate. We have performed simulations of global land cover change using the NCAR CAM3 atmospheric general circulation model coupled to a slab ocean model. We find that global replacement of current vegetation by trees would lead to a global mean warming of 1.3°C, nearly 60% of the warming produced under a doubled CO2 concentration, while replacement by grasslands would result in a cooling of 0.4°C. It has been previously shown that boreal forestation can lead to warming; our simulations indicate that mid‐latitude forestation also could lead to warming. These results suggest that more research is necessary before forest carbon storage should be deployed as a mitigation strategy for global warming.
Computer simulation of two‐phase immiscible fluid motion in unsaturated complex fractures using a volume of fluid method
Authors: Huang Hai , Meakin Paul , Liu Moubin
Published: December 2005

Complex fluid behavior in unsaturated fracture and fracture networks, such as film flow, the migration, fragmentation, and coalescence of droplets, and rivulet flow with or without meandering or pulsation, has been widely observed in laboratory experiments. In this study, a modified two‐dimensional volume of fluid (VOF) method was used to simulate liquid motion in partially saturated fracture apertures under a variety of flow conditions. This modeling approach systematically incorporates the effects of inertial forces, viscosity, gravity acting on the fluid densities, fracture wall wetting, and the pressure drop across curved fluid‐fluid interfaces due to surface tension. This allows us to obtain a better understanding of the fundamental physics governing unsaturated fluid flow in fracture apertures. The VOF method is able to handle the complex dynamics of fluid‐fluid interfaces and free surfaces in unsaturated fractures by using a fixed Eulerian grid. Fragmentation and coalescence of the fluids are automatically handled without resorting to complex adaptive mesh refinement or interface repairing algorithms. The wetting of fracture walls was modeled by imposing contact angles near the contact lines (contact points in two‐dimensional simulations), and different contact angles were automatically chosen depending on whether the liquid interface is advancing, receding, or essentially stationary. The qualitative agreements between the numerical simulations and complex multiphase fluid dynamics reported in laboratory experiments clearly demonstrate the potential value of the VOF method for the mechanistically based modeling of immiscible liquid motion in unsaturated fracture networks.
The spin structure of excitons and biexcitons in semiconductor quantum wells
Authors: Ostatnický T. , Gilliot P. , Hönerlage B.
Published: December 2005

We report on symmetry-based calculations of the spin structure of excitons and biexcitons in quantum wells. Depending on the point-group symmetry of the material and the growth directions of the quantum wells, we derive Hamiltonians appropriate for the description of excitons and biexcitons. We show possible paths of coherent spin-flip processes of a particle and their consequences for experimental observations.
Magnetic hyperfine fields in the room-temperature dilute magnetic semiconducting alloy Fe:Sb1−xSex
Authors: Somayajulu D. R. S. , Chawda Mukesh , Patel Narendra , Sarkar Mitesh , Sebastian K. C. , Venugopalan K. , Gupta A.
Published: December 2005

A dilute quantity of Fe (0.008) was doped into V-VI (Sb1−xSex) for X=0 to 0.50 alloys based on Sb semimetal. Hall measurements showed that the materials were n-type semiconductors for X=0.01 to 0.10 and the charge carrier densities increased from 4.2×1019cm−3 to 1.142×1021cm−3 in this region. For higher concentration of Se (X=0.50), the charge carrier densities decreased dramatically to 2.1×1015. For X=0, Fe showed no magnetic moment. For X=0.01 to 0.1 two magnetic sites (A and B) were observed at room temperature by Mossbauer measurement. Site A appears to be an SeFeSb, type ternary alloy. p-d interaction and carrier-induced polarization seem to be responsible for the magnetic interaction at this site (A). Tc (for Site A) was measured to be ∼573K. Similar behavior was observed for Fe(0.002). Site B Mossbauer parameters coincide with those of Fe7Se8.
Constraints on the mixing of bipartite states
Authors: Chen Hao
Published: December 2005

A mixed state may be represented in many different ways as a mixture of pure states ρ=∑pi∣ψi⟩⟨ψi∣. The mixing problem in quantum mechanics asks the characterization of the probability distribution (pi) and the mixed states (ρi) such that ρ=∑piρi for any given mixed state ρ. Some constraints based on eigenvalues of the mixed states are established in uni-party case [see Nielsen, Phys. Rev. A. 63, 052308 (2000), 63, 022144 (2000), Nielsern and Vidal Quantum Inf. Comput. 1 76 (2001)]. We develop some new invariant sets for bipartite mixed states under local unitary operations, which are independent of eigenvalues, and prove some strong constraints based on these invariant sets for the mixing problem in bipartite case. This exhibits a remarkable difference from the uni-party case.
Annealing-environment effects on the properties of CoPt nanoparticles formed in single-crystal Al2O3 by ion implantation
Authors: White C. W. , Withrow S. P. , Budai J. D. , Thomas D. K. , Williams J. M. , Meldrum A. , Sorge K. D. , Thompson J. R. , Ownby G. W. , Wendelken J. F. , Boatner L. A.
Published: December 2005

The ion implantation of nearly equal doses of Co and Pt into a single-crystal Al2O3 host followed by thermal annealing leads to the formation of nanoparticles whose phase, structure, and physical properties are strongly dependent on the annealing environment. Annealing in 96%Ar+4%H2 gives rise to ferromagnetic, chemically ordered CoPt nanoparticles with the L10 structure and a magnetic coercivity that can exceed 10kOe at 5K. Annealing in O2 (or in Ar) does not result in the formation of a CoPt alloy. Instead, the implanted Pt precipitates to form oriented elemental Pt nanoparticles, and the implanted Co combines with oxygen to form Co3O4 oxide nanoparticles. Annealing in ultrahigh-vacuum conditions results in a mixture of phases including CoPt3 and Co3O4 and possibly Co. The results obtained for Co+Pt-implanted Al2O3 are compared with the previous results for Fe+Pt-implanted Al2O3 annealed in similar environments.
Defect-driven inhomogeneities in Ni∕4H–SiC Schottky barriers
Authors: Tumakha S. , Ewing D. J. , Porter L. M. , Wahab Q. , Ma X. , Sudharshan T. S. , Brillson L. J.
Published: December 2005

Nanoscale depth-resolved cathodoluminescence spectroscopy (DRCLS) of Ni diode arrays on 4H-SiC epitaxial wafers reveals a striking correspondence between deep level defects and electrical transport measurements on a diode-by-diode basis. Current-voltage measurements display both ideal and nonideal diode characteristics due to multiple barriers within individual contacts. Near-interface DRCLS demonstrates the presence of three discrete midgap defect levels with 2.2, 2.45, and 2.65eV emission energies whose concentrations vary on a submicron scale among and within individual diodes, correlating with barrier inhomogeneity. These results also suggest that SiC native defect levels can account for the maximum range of n-type barrier heights.
Tera-sample per second real-time waveform digitizer
Authors: Han Yan , Boyraz Ozdal , Jalali Bahram
Published: December 2005

We demonstrate a real-time transient waveform digitizer with a record 1tera-samplepersecond sampling rate. This is accomplished by using a photonic time stretch preprocessor which slows down the electrical waveform before it is captured by an electronic digitizer.
Simulations of dual rf-biased sheaths and ion energy distributions arriving at a dual rf-biased electrode
Authors: Guan Zhen-Qun , Dai Zhong-Ling , Wang You-Nian
Published: December 2005

Spatio-temporal characteristics of collisionless dual rf-biased sheaths and ion energy distributions (IEDs) impinging on a dual rf-biased electrode are studied with a self-consistent one-dimensional hydrodynamic model. The model includes all the time-dependent terms in the ion fluid equations to ensure that it can describe the sheath dynamics over a wide range of frequencies. In addition, an equivalent circuit model is used to self-consistently determine the relationship between the instantaneous sheath thickness and the instantaneous voltage on the dual rf-biased electrode. The numerical results show that, due to dual radiofrequencies being applied to an electrode, the sheath structures and parameters of dual rf-biased sheaths are different from those in the case of single frequency-biased plasma. Multiple peaks appear in the IEDs arriving at the dual rf-biased electrode rather than a bimodal shape as the IEDs are incident onto a single frequency-biased electrode. It is also shown that some parameters such as the bias frequency and power of the lower-frequency source as well as the phase difference between the lower-frequency wave and the higher-frequency wave are crucial for determining the dual rf sheath structure and the shape of IEDs.
Self-assembled InAs quantum dots on patterned GaAs(001) substrates: Formation and shape evolution
Authors: Kiravittaya S. , Rastelli A. , Schmidt O. G.
Published: December 2005

We report on the formation of ordered and size homogeneous InAs quantum dot (QD) arrays on patterned GaAs(001) substrates. A material depletion region is observed around the patterned area while a long-range homogeneous distribution of QDs is found inside the patterned area. A sample with less InAs deposition shows a gradient in the material distribution over the patterned area. Based on these observations we propose a simple model to describe the QD formation in the patterned area. The QD shape evolution is also investigated and discussed.
Down-regulation of the retinoblastoma tumor suppressor by the hepatitis C virus NS5B RNA-dependent RNA polymerase
Authors: Munakata Tsubasa , Nakamura Mitsuyasu , Liang Yuqiong , Li Kui , Lemon Stanley M.
Published: December 2005

The retinoblastoma tumor-suppressor protein (Rb) plays a critical role in controlling cellular proliferation and apoptosis by regulating E2F transcription factors. Rb is a key target of oncoproteins expressed by DNA tumor viruses, but RNA viruses are not known to regulate Rb function. Here, we show that Rb abundance is negatively regulated in cells containing replicating genomic RNA from hepatitis C virus, a human virus strongly associated with hepatocellular carcinoma. The viral RNA-dependent RNA polymerase NS5B forms a complex with Rb, targeting it for degradation and resulting in reduction of Rb abundance, activation of E2F-responsive promoters, and cell proliferation. NS5B contains a conserved Leu-x-Cys/Asn-x-Asp motif that is homologous to Rb-binding domains in the oncoproteins of DNA viruses. This domain overlaps the polymerase active site, and mutations within it abrogate Rb binding and reverse the effects of NS5B on E2F promoter activation and cell proliferation. These findings suggest a unique link between an oncogenic RNA virus implicated in the development of liver cancer and a critically important tumor-suppressor protein.
Structure of peptide sex pheromone receptor PrgX and PrgX/pheromone complexes and regulation of conjugation inEnterococcus faecalis
Authors: Shi Ke , Brown C. Kent , Gu Zu-Yi , Kozlowicz Briana K. , Dunny Gary M. , Ohlendorf Douglas H. , Earhart Cathleen A.
Published: December 2005

Many bacterial activities, including expression of virulence factors, horizontal genetic transfer, and production of antibiotics, are controlled by intercellular signaling using small molecules. To date, understanding of the molecular mechanisms of peptide-mediated cell-cell signaling has been limited by a dearth of published information about the molecular structures of the signaling components. Here, we present the molecular structure of PrgX, a DNA- and peptide-binding protein that regulates expression of the conjugative transfer genes of theEnterococcus faecalisplasmid pCF10 in response to an intercellular peptide pheromone signal. Comparison of the structures of PrgX and the PrgX/pheromone complex suggests that pheromone binding destabilizes PrgX tetramers, opening a 70-bp pCF10 DNA loop required for conjugation repression.
A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt–Oram syndrome
Authors: Murakami Masao , Nakagawa Masayo , Olson Eric N. , Nakagawa Osamu
Published: December 2005

The T-box transcription factor TBX5 plays essential roles in cardiac and limb development. Various mutations in the
TBX5
gene have been identified in patients with Holt–Oram syndrome, which is characterized by congenital defects in the heart and upper extremities. In this study, we identified a WW-domain-containing transcriptional regulator TAZ as a potent TBX5 coactivator. TAZ directly associates with TBX5 and markedly stimulates TBX5-dependent promoters by interacting with the histone acetyltransferases p300 and PCAF. YAP, a TAZ-related protein with conserved functional domains, also stimulates TBX5-dependent transcription, possibly by forming a heterodimer with TAZ. TBX5 lacks a PY motif, which mediates the association of other proteins with TAZ, and interacts with TAZ through multiple domains including its carboxyl-terminal structure. Truncation mutants of TBX5 identified in patients with Holt–Oram syndrome were markedly impaired in their ability to associate with and be stimulated by TAZ. These findings reveal key roles for TAZ and YAP in the control of TBX5-dependent transcription and suggest the involvement of these coactivators in cardiac and limb development.
Opiine parasitoids (Hymenoptera: Braconidae) of tropical fruit flies (Diptera: Tephritidae) of the Australian and South Pacific region
Authors: Carmichael A.E. , Wharton R.A. , Clarke A.R.
Published: December 2005

Opiine wasps are parasitoids of dacine fruit flies, the primary horticultural pests of Australia and the South Pacific. A taxonomic synopsis and distribution and host records (44% of which are new) for each of the 15 species of dacine-parasitizing opiine braconids found in the South Pacific is presented. Species dealt with are Diachasmimorpha hageni (Fullaway), D. kraussii (Fullaway), D. longicaudata (Ashmead), D. tryoni (Cameron), Fopius arisanus (Sonan), F. deeralensis (Fullaway), F. ferrari Carmichael & Wharton sp. n., F. illusorius (Fischer) comb. n., F. schlingeri Wharton, Opius froggatti Fullaway, Psyttalia fijiensis (Fullaway), P. muesebecki (Fischer), P. novaguineensis (Szépligeti) and Utetes perkinsi (Fullaway). A potentially undescribed species, which may be a colour morph of F. vandenboschi (Fullaway), is diagnosed but not formally described. Fopius vandenboschi sensu stricto, Diachasmimorpha fullawayi Silvestri, Psyttalia concolor Szépligeti and P. incisi Silvestri have been liberated into the region but are not considered to have established: a brief diagnosis of each is included. Biosteres illusorius Fischer is formally transferred to the genus Fopius. A single opiine specimen reared from a species of Bactrocera (Bulladacus) appears to be Utetes albimanus (Szépligeti), but damage to this specimen and to the holotype (the only previously known specimen) means that this species remains unconfirmed as a fruit fly parasite: a diagnosis of U. cf. albimanus is provided. Psyttalia novaguineensis could not be adequately separated from P. fijiensis using previously published characterizations and further work to resolve this complex is recommended. A key is provided to all taxa.
DNA markers for identifying biotypes B and Q of Bemisia tabaci (Hemiptera: Aleyrodidae) and studying population dynamics
Authors: Khasdan V. , Levin I. , Rosner A. , Morin S. , Kontsedalov S. , Maslenin L. , Horowitz A.R.
Published: December 2005

The two most widespread biotypes of Bemisia tabaci (Gennadius) in southern Europe and the Middle East are referred to as the B and Q-type, which are morphologically indistinguishable. In this study various DNA markers have been developed, applied and compared for studying genetic diversity and distribution of the two biotypes. For developing sequence characterized amplified regions (SCAR) and cleaved amplified polymorphic sequences (CAPS) techniques, single random amplified polymorphic DNA (RAPD) fragments of B and Q biotypes, respectively, were used. The CAPS were investigated on the basis of nuclear sodium channel and the mitochondrial cytochrome oxidase I genes (mtCOI) sequences. In general, complete agreement was found between the different markers used. Analysis of field samples collected in Israel for several years, using these markers, indicated that the percentage of the Q biotype tends to increase in field populations as time progresses. This may be attributed to the resistance of the Q biotype to neonicotinoids and pyriproxyfen and the susceptibility of the B biotype to these insecticides.
Comparative studies on populations of Pauesia juniperorum (Hymenoptera: Braconidae), a biological control agent for Cinara cupressivora (Hemiptera: Aphididae)
Authors: Kairo M.T.K. , Murphy S.T.
Published: December 2005

Pauesia juniperorum (Starý), a solitary endoparasitoid which attacks several Cinara spp. in the subgenus Cupressobium, was introduced into Africa for the control of the cypress aphid Cinara cupressivora Watson & Voegtlin (previously identified as Cinara cupressi (Buckton)) and is now established. Data on its biology including a comparison of populations from different hosts and geographical locations are presented. From the UK this consisted of populations reared from Cinara cupressivora, Cinara fresai Blanchard and Cinara juniperi De Geer, and from France, Cinara ?fresai. Between different populations, the duration of development varied within a narrow range (15.5–18.1 days) at 22°C. Data on duration of development over a range of temperatures (15–26°C) for two populations, from the UK and France ranged between 14.0–31.4 days for males and 14.7–32.8 days for females. The threshold temperature for development was 6.2°C and 4.1°C for the populations from the UK and France, respectively. The mean egg load for different populations ranged between 46.4 and 78.5 eggs. The host species had a significant effect on egg load which was directly related to size of the respective host aphids. The lowest egg load was recorded on specimens reared from C. cupressivora which was the smallest aphid. The population from the UK had a higher intrinsic rate of increase (0.232) than the one from France (0.207).
Impact of health service provision on mothers and infants in a rural village in North West Frontier Province, Pakistan
Authors: Northrop-Clewes Christine A , Ahmad Nisar , Paracha Parvez I , Thurnham David I
Published: December 2005

Objective:

The objective of this paper is to examine the impact of the Health Service Research Project of the Pakistan Medical Research Council (PMRC) on mothers and infants in Budhni village, North West Frontier Province (NWFP), Pakistan.

Methods:

Information from the PMRC records on the socioeconomic and demographic situation over the last 10 years and anthropometric measurements made on all infants from 1986–96 were collected and analysed.

Results:

The demographic data showed a number of changes, namely a reduction in birth rate and improvements in perinatal, neonatal, infant and child mortality rates. Literacy in the village was poor (27 and 39% literate in 1986 and 1996, respectively) and female literacy showed no improvement (14%). Improvements in sanitation and in the water supply introduced by the PMRC had limited success, as clean water was subsequently contaminated by unclean hands and utensils, and 50% of the population continued to use open fields for sanitation. In 1986 only 27% of children 0–5 years were vaccinated, but by 1996, 96% of children had completed polio, diphtheria/pertussis/tetanus (DPT) and bacille Calmette-Guérin (BCG) vaccination programmes and 95% of women of child-bearing age were vaccinated against tetanus. Protection against tetanus reduced neonatal deaths and from 1333 onwards there have been no further cases.

Anthropometric data for the period 1986–96 for infants (0–24 months) showed that at birth the majority of infants were close to the 50th National Centre for Health Statistics (NCHS) centile for weight and length, and only 5% of birth-weights were less than 2.5 kg. Growth charts showed faltering in length and weight and by 24-months length in both boys and girls was below the 3rd NCHS centile and weights were just above.

Conclusions:

Reductions in child mortality have occurred over the period 1986–96. However, the slow progress in adopting hygienic practices, despite health education, and the low literacy rates, particularly in women, may hamper continued improvement.
UK consumer attitudes, beliefs and barriers to increasing fruit and vegetable consumption
Authors: Cox David N , Anderson Annie S , Lean Michael EJ , Mela David J
Published: December 2005

Objective:

To assess attitudes, predictors of intention, and identify perceived barriers to increasing fruit and vegetable (F&V) intakes.

Design:

UK nationwide postal survey utilizing the theory of planned behaviour.

Subjects:

Stratified (by social class and region) random sample of 2020 UK adults providing a modest response rate of 37% (n = 741).

Results:

Belief measures (e.g. health, cost, taste, etc.) were strongly associated with overall attitudes which were reported as being largely favourable towards fruit, vegetables and, to a lesser extent, vegetable dishes, and were strongly associated with reported intention to increase consumption. Subjects reported they could increase their consumption, but this was only weakly associated with intention to do so. Approximately 50% of respondents reported an intention to increase intakes. Social pressure was strongly associated with reported intention to increase; however, scores indicated low perceived social pressure to change. Evidence of unrealistic optimism concerning perceived intakes and the perceived high cost of fruit may also act as barriers.

Conclusions:

Results from this study suggest a lack of perceived social pressure to increase F&V intakes and suggests that public health efforts require stronger and broader health messages that incorporate consumer awareness of low present consumption.
Curriculum design for professional development in public health nutrition in Britain
Authors: Landman Jacqueline , Buttriss Judith , Margetts Barrie
Published: December 2005

Objective:

To describe how the Nutrition Society developed public health nutrition as a profession between 1992 and 1997, and to analyse the influences propelling on this professionalization.

Design:

Qualitative case study.

Setting:

Britain.

Results:

The Nutrition Society of Britain consulted with various stakeholders (such as dietitians, researchers, professionals and practitioners and educators from the UK, and latterly from mainland Europe) to build a consensus about the definition, roles and functions of public health nutritionists and the need for, and scope of, this new profession. Building on this consensus, the Society developed a curriculum in line with British national nutrition policy. Analysis shows that the design and philosophy of the curriculum is explicitly international and European in orientation, in keeping with the tradition of the discipline and the Society. The curriculum is designed in terms of specialist competencies in public health nutrition, defining competency so that registered public health nutritionists are advanced practitioners or leaders: this is in keeping with contemporary trends in professional education generally and as expressed by the UNU/IUNS and at Bellagio, in nutrition in particular.

Conclusions:

Despite a unique relationship with British state and policy, this case of professionalization contributes to contemporary international inter- and intraprofessional debates about the nature of public health nutrition and is consistent with professional educational theory.
Kale anaemia
Authors: Greenhalgh J. F. D.
Published: December 2005

The two main types of kale grown in Britain, marrowstem and thousandhead,
both belong to the species Brassica oleracea L. Marrowstem
is a thick-stemmed plant, 1–1·5 m tall, whereas thousandhead has a higher
ratio of leaf to stem and is a shorter plant. Kale is sown in late spring
and normally harvested from October to February, thousandhead being the more
resistant to frost. The crop yields about 50 000 kg green matter per hectare
(7000 kg dry matter) and is either consumed in situ or cut
and carried to housed animals. Cattle are rarely fed on kale alone, but
sheep may be; when kale is grazed its consumption is not closely controlled.
Kale is grown widely in Britain and north Europe generally, and also in New
Zealand.
Chronic copper toxicity of ruminants
Authors: Todd J. R.
Published: December 2005

There has been an active interest in the toxicology of copper since the
middle of the 19th century and a review by Davenport (1953) covers the early
work on the hazard to man and animals of both the acute and chronic forms.
Review material specific to chronic copper poisoning in farm livestock has
also been published by Broughton & Hardy (1934), Eden (1940), Todd
(1962) and Bull (1964).

The first description of true chronic copper poisoning in farm animals would
seem to be that of Mallory (1925) who produced the condition experimentally
in sheep. Beijers (1932) described similar symptoms in sheep grazing
orchards which had been sprayed with a copper fungicide, and 2 years later
Broughton & Hardy (1934) published their detailed experimental
investigations showing the dangers of excessive copper intakes to sheep. The
similarity between the symptoms described in these reports and those of
‘yellows’ or ‘toxaemic jaundice’ in Australia was recognized (Bull, 1964)
and the experiments of Albiston, Bull, Dick & Keast (1940) confirmed
that this naturally-occurring condition was of similar origin. The
importance of chronic copper poisoning as a nutritional hazard was,
therefore, fully established.
Urinary calculi in ruminants
Authors: Field A. C.
Published: December 2005

Urolithiasis is not at present an important problem for the livestock
industry in the United Kingdom, but the probable introduction of more
intensive systems of management may change this position. The rapid
fattening of male animals with high-energy diets predisposes to formation of
phosphatic calculi and obstructive urolithiasis in the feed lot system of
the USA and it is a form of this type of management which is most likely to
be introduced to this country. For this reason, this review will be limited
to the problem of phosphatic calculus formation, although other calculi,
especially siliceous forms cause economic loss in extensive areas of the
world.
Protein nutrition and wound healing
Authors: Garrow J. S.
Published: December 2005

In normal young men, in whom the calorie requirements are fully met, an
intake of about 50 g protein per day promotes nitrogen balance, and little
additional storage results even from much larger protein intakes (Galloway
& Spector, 1954). Chittenden maintained that an adult who adopted the
intake of 120 g per day suggested by Voit, or who advised others to do so,
was ‘encouraging individual and racial suicide’ (Cathcart, 1912), and the
animal experiments of Ross show that by all objective criteria, except that
of body-weight, the rats whose dietary intake is restricted fare better than
those allowed unlimited quantities of a diet of good quality (Ross, 1961;
Ross & Bras, 1965).
Least absolute regression network analysis of the murine osteoblast differentiation network
Authors: van Someren E. P. , Vaes B. L. T. , Steegenga W. T. , Sijbers A. M. , Dechering K. J. , Reinders M. J. T.
Published: December 2005

Motivation: We propose a reverse engineering scheme to discover genetic regulation from genome-wide transcription data that monitors the dynamic transcriptional response after a change in cellular environment. The interaction network is estimated by solving a linear model using simultaneous shrinking of the least absolute weights and the prediction error.

Results: The proposed scheme has been applied to the murine C2C12 cell-line stimulated to undergo osteoblast differentiation. Results show that our method discovers genetic interactions that display significant enrichment of co-citation in literature. More detailed study showed that the inferred network exhibits properties and hypotheses that are consistent with current biological knowledge.

Availability: Software is freely available for academic use as a Matlab package called GENLAB:

Contact:  E.P.vanSomeren@tudelft.nl

Supplementary information: Additional data, results and figures can be found at
Identification of genes associated with mutacin I production in Streptococcus mutans using random insertional mutagenesis
Authors: Tsang Phoebe , Merritt Justin , Nguyen Trang , Shi Wenyuan , Qi Fengxia
Published: December 2005

Streptococcus mutans is a major pathogen implicated in dental caries. Its virulence is enhanced by its ability to produce bacteriocins, called mutacins, which inhibit the growth of other Gram-positive bacteria. The goal of this study is to use a random insertional mutagenesis approach to search for genes that are associated with mutacin I production in the virulent strain UA140. A random insertional mutagenesis library consisting of 11 000 clones was constructed and screened for a mutacin-defective phenotype. Mutacin-defective clones were isolated, and their insertion sites were determined by PCR amplification or plasmid rescue followed by sequencing. A total of twenty-five unique genes were identified. These genes can be categorized into the following functional classes: two-component sensory systems, stress responses, energy metabolism and central cellular processes. Several conserved hypothetical proteins with unknown functions were also identified. These results suggest that mutacin I production is stringently controlled by diverse and complex regulatory pathways.
Transcriptional analysis of the acid tolerance response in Streptococcus pneumoniae
Authors: Martín-Galiano Antonio J. , Overweg Karin , Ferrándiz Maria J. , Reuter Mark , Wells Jerry M. , de la Campa Adela G.
Published: December 2005

Streptococcus pneumoniae, one of the major causes of morbidity and mortality in humans, faces a range of potentially acidic conditions in the middle and late stages of growthin vitro, in diverse human fluids during the infection process, and in biofilms present in the nasopharynx of carriers.S. pneumoniaewas shown to develop a weak acid tolerance response (ATR), where cells previously exposed to sublethal pHs (5·8–6·6) showed an increased survival rate of up to one order of magnitude after challenge at the lethal pH (4·4, survival rate of 10−4). Moreover, the survival after challenge of stationary phase cells at pH 4·4 was three orders of magnitude higher than that of cells taken from the exponential phase, due to the production of lactic acid during growth and increasing acidification of the growth medium until stationary phase. Global expression analysis after short-term (5, 15 and 30 min, the adaptation phase) and long-term (the maintenance phase) acidic shock (pH 6·0) was performed by microarray experiments, and the results were validated by real-time RT-PCR. Out of a total of 126 genes responding to acidification, 59 and 37 were specific to the adaptation phase and maintenance phase, respectively, and 30 were common to both periods. In the adaptation phase, both up- and down-regulation of gene transcripts was observed (38 and 21 genes, respectively), whereas in the maintenance phase most of the affected genes were down-regulated (34 out of 37). Genes involved in protein fate (including those involved in the protection of the protein native structure) and transport (including transporters of manganese and iron) were overrepresented among the genes affected by acidification, 8·7 and 24·6 % of the acid-responsive genes compared to 2·8 % and 9·6 % of the genome complement, respectively. Cross-regulation with the response to oxidative and osmotic stress was observed. Potential regulatory motifs involved in the ATR were identified in the promoter regions of some of the regulated genes.
A secreted lipase encoded by LIP1 is necessary for efficient use of saturated triglyceride lipids in Fusarium graminearum
Authors: Feng Jie , Liu Guosheng , Selvaraj Gopalan , Hughes Geoffrey R. , Wei Yangdou
Published: December 2005

A triglyceride lipase geneLIP1was identified in the genome ofFusarium graminearumstrain PH-1. The predicted protein encoded byLIP1contains 591 amino acid residues with a putative N-terminal signal peptide and shows 57 and 40–44 % identity to aBotrytis cinerealipase and fiveCandida rugosalipases, respectively. Yeast cells overexpressing LIP1 showed lipolytic activity against a broad range of triglyceride substrates. Northern blot analyses revealed that expression ofLIP1was activatedin plantaduring the fungal infection process.LIP1expression was strongly induced in minimal medium supplemented with wheatgerm oil, but only weakly induced by olive oil and triolein. In contrast, supplementation with other carbon sources, including glucose, sucrose, apple pectin and wheat cell-wall material, did not induceLIP1expression. Saturated fatty acids were the strongest inducers forLIP1expression and this induction was suppressed proportionally by the presence of the unsaturated fatty acid. To determine the potential function ofLIP1, gene replacement was conducted on strain PH-1. When compared with wild-type PH-1, ΔLIP1mutants showed greatly reduced lipolytic activities at the early stage of incubation on minimal medium supplemented with either saturated or unsaturated lipid as the substrate, indicating thatLIP1encodes a secreted lipase for exogenous lipid hydrolysis. Moreover, the ΔLIP1mutants exhibited growth deficiency on both liquid and solid minimal media supplemented with the saturated triglyceride tristearin as the sole carbon source, suggesting thatLIP1is required for utilization of this substance. Despite these differences, no variation in disease symptoms between the ΔLIP1mutants and the wild-type strain was observed on susceptible cereal hosts.
Concomitant hairy cell and acute myeloid leukemia
Authors: Rimner T. , Went P. , Tichelli A. , Gratwohl A.
Published: December 2005

Abstract:  Secondary malignancies in patients with hairy cell leukemia (HCL) are well described and treatment of HCL is discussed as their cause. We describe a 58‐yr‐old patient who presented with both acute myeloid leukemia (AML) and HCL at the same time. Treatment with cladribine, daunorubicin and cytosine arabinoside, followed by autologous stem cell transplantation, induced complete remission of AML and hematologic remission of HCL for 22 months, when he relapsed with AML. This concomitant occurrence of AML and HCL is suggestive of a genetic predisposition rather then coincidence or relation to purine analoga.
Stimulation of epidermal calcium gradient loss and increase in TNF‐α and IL‐1α expressions by glycolic acid in murine epidermis
Authors: Jeong Se Kyoo , Ko Joo Yeon , Seo Jeong Taek , Ahn Sung Ku , Lee Chang Woo , Lee Seung Hun
Published: December 2005

Abstract:  In a previous study, we reported that α‐hydroxy acids (AHA), such as glycolic acid and lactic acid, did not induce any significant changes in transepidermal water loss for normal murine skin. The ultrastructural observations, however, showed that the extent of lamellar body exocytosis significantly increased. Because AHA can theoretically decrease the calcium ion concentration by chelation, topical AHA may induce the loss of epidermal calcium gradient by lowering the calcium ion concentration in the granulocytes and, subsequently, induce lamellar body secretion. The aim of this study is to verify that glycolic acid could modulate the epidermal calcium gradient and increase lamellar body exocytosis. Seventy per cent of glycolic acid aqueous solution was applied to the normal skin of hairless mice and biochemical and morphological studies were performed. The loss of epidermal calcium gradient was observed in glycolic‐acid‐applied skin of hairless mice and subsequent barrier function recovery processes, such as an increase in lamellar body secretion, were observed. The extracellular glycolic acid was found to inhibit the change in intracellular calcium ion concentration in response to extracellular calcium ion concentration changes in the cultured mouse keratinocyte in vitro. The protein and mRNA expressions of tumour necrosis factor‐α and interleukin‐1α in the murine epidermis were significantly increased after glycolic acid application. An in vitro study using cultured keratinocytes suggested that glycolic acid could lower the calcium ion concentration, at least in part, through the chelating effects of the glycolic acid on the cationic ions.
Ex vivo analysis of desmoglein 1‐responsive T‐helper (Th) 1 and Th2 cells in patients with pemphigus foliaceus and healthy individuals
Authors: Gebhard Kerstin L. , Veldman Christian M. , Wassmuth Ralf , Schultz Erwin , Schuler Gerold , Hertl Michael
Published: December 2005

Abstract:  Pemphigus foliaceus (PF) is a severe autoimmune bullous disorder, characterized by autoantibodies (autoAb) against desmoglein 1 (Dsg1). As T cells may be critical in the pathology of PF, the aim of the present study was to identify and characterize autoaggressive T‐helper cells reactive to Dsg1 in PF patients and healthy individuals. Eight patients with the clinical diagnosis of PF and six HLA class II‐matched healthy individuals were examined. By magnetic cell‐sorting (MACS) cytokine‐secretion assay, Dsg1‐responsive T‐helper (Th) 1 and Th2 cells were isolated and cloned by limiting dilution. The generated T‐cell clones (TCC) were characterized regarding proliferative response, TCR Vβ‐chain usage, and cytokine profile upon in vitro stimulation with Dsg1. Both Dsg1‐reactive Th1 and Th2 cells were detected in PF patients and controls at similar frequencies. A total of 15 Th1 and Th2 clones were isolated from patients and 27 TCC from healthy controls. Analysis of TCR Vβ‐chain usage of autoreactive T cells from both groups revealed no predominance of a specific Vβ chain. Noteworthy, the isolated TCC showed a polarized Th1‐ or Th2‐like phenotype upon in vitro culture and stable expression of Th1 or Th2 cytokines during long‐term in vitro culture. In summary, our data demonstrate that T‐cell autoreactivity against Dsg1 is not restricted to patients with PF. Moreover, both Th1 and Th2 cells were present in patients and healthy donors, suggesting that the loss of B‐cell tolerance against Dsg1 in PF is not exclusively determined by the presence of autoaggressive T cells.
Genetic mosaicism in basal cell carcinoma
Authors: Asplund Anna , Sivertsson Åsa , Bäckvall Helena , Ahmadian Afshin , Lundeberg Joakim , Ponten Fredrik
Published: December 2005

Abstract:  Human basal cell cancer (BCC) shows unique growth characteristics, including a virtual inability to metastasize, absence of a precursor stage and lack of tumour progression. The clonal nature of BCC has long been a subject for debate because of the tumour growth pattern. Despite a morphologically multifocal appearance, genetic analysis and three‐dimensional reconstructions of tumours have favoured a unicellular origin. We have utilized the X‐chromosome inactivation assay in order to examine clonality in 13 cases of BCC. Four parts of each individual tumour plus isolated samples of stroma were analysed following laser‐assisted microdissection. In 12/13 tumours, the epithelial component of the tumour showed a monoclonal pattern suggesting a unicellular origin. Surprisingly, one tumour showed evidence of being composed of at least two non‐related monoclonal clones. This finding was supported by the analysis of the ptch and p53 gene. Clonality analysis of tumour stroma showed both mono‐ and polyclonal patterns. A prerequisite for this assay is that the extent of skewing is determined and compensated for in each case. Owing to the mosaic pattern of normal human epidermis, accurate coefficients are difficult to obtain; we, therefore, performed all analyses both with and without considering skewing. This study concludes that BCC are monoclonal neoplastic growths of epithelial cells, embedded in a connective tissue stroma at least in part of polyclonal origin. The study results show that what appears to be one tumour may occasionally constitute two or more independent tumours intermingled or adjacent to each other, possibly reflecting a local predisposition to malignant transformation.
DeoxyArbutin: a novel reversible tyrosinase inhibitor with effective in vivo skin lightening potency
Authors: Boissy Raymond E. , Visscher Marty , DeLong Mitchell A.
Published: December 2005

Abstract:  Modulation of melanogenesis in the melanocytes can be achieved using chemicals that share structural homologies with the substrate tyrosine and as thus competitively inhibit the catalytic function of tyrosinase. We have developed a new tyrosinase inhibitor, deoxyArbutin (dA), based on this premise. DeoxyArbutin demonstrates effective inhibition of mushroom tyrosinase in vitro with a Ki that is 10‐fold lower that hydroquinone (HQ) and 350‐fold lower than arbutin. In a hairless, pigmented guinea pig model, dA demonstrated rapid and sustained skin lightening that was completely reversible within 8 weeks after halt in topical application. In contrast, HQ induced a short but unsustained skin lightening effect whereas kojic acid and arbutin exhibit no skin lightening effect. Results from a panel of safety tests supported the overall establishment of dA as an actionable molecule. In a human clinical trial, topical treatment of dA for 12 weeks resulted in a significant or slight reduction in overall skin lightness and improvement of solar lentigines in a population of light skin or dark skin individuals, respectively. These data demonstrate that dA has potential tyrosinase inhibitory activity that can result in skin lightening and may be used to ameliorate hyperpigmentary lesions.
Stratum corneum hydration and flexibility are useful parameters to indicate clinical severity of congenital ichthyosis
Authors: Tomita Yuki , Akiyama Masashi , Shimizu Hiroshi
Published: December 2005

Abstract:  To determine any correlation between the stratum corneum barrier function and the phenotypic severity of congenital ichthyosis, we studied stratum corneum hydration, flexibility, thickness and transepidermal water loss (TEWL) in patients with congenital ichthyosis. Seven patients with congenital ichthyosis aged 2–46 years and age‐matched controls were included in the present study. We divided seven patients into two groups; patients with non‐bullous type (non‐bullous congenital ichthyosiform erythroderma patients) and patients with the bullous type of congenital ichthyosis (bullous congenital ichthyosiform erythroderma and ichthyosis bullosa of Siemens). Stratum corneum hydration, thickness and flexibility were measured using a Corneometer ASA‐M2. The stratum corneum thickness was also examined using a skin biopsy technique. TEWL was measured using Evaporimeter AS‐TW1. The clinical severity of ichthyosis phenotype was evaluated using a visual analogue scale (VAS). Stratum corneum hydration and flexibility were significantly reduced in both congenital ichthyosis patient groups. Stratum corneum thickness was significantly increased in both groups. In the patient group with non‐bullous congenital ichthyosis, significant negative correlations were confirmed between the VAS score and stratum corneum hydration and between the VAS score and flexibility. A significant, positive correlation was also observed between the VAS score and stratum corneum thickness. There was a positive correlation between the VAS score and TEWL on both the extensor and flexor sides of the forearm and back. We conclude that stratum corneum hydration, flexibility and thickness measured by the corneometer, and TEWL on the arm may be a useful indicator of the severity of ichthyosis phenotype.
Improved detection of allergen‐specific T‐cell responses in allergic contact dermatitis through the addition of ‘cytokine cocktails’
Authors: Moed Helen , Von Blomberg Mary , Bruynzeel Derk P. , Scheper Rik , Gibbs Susan , Rustemeyer Thomas
Published: December 2005

Abstract: The gold standard for the diagnosis of allergic hypersensitivity is skin patch testing with the suspected allergens. This diagnostic tool, however, has distinct disadvantages, and therefore the development of alternative or complementaryin vitrotests is of great importance. In this study, we evaluate the applicability of anin vitrotest method, as developed earlier for nickel allergy, to detect allergen‐specific T cells in the blood of patients allergic to frequent sensitizers (chromate, cobalt, paraphenylenediamine, fragrances and chloromethyl‐isothiazolinone). Peripheral blood mononuclear cells (PBMCs) of allergic patients and healthy controls were cultured in the absence or presence of allergen. Additionally, type 1 (IL‐7 and IL‐12) or type 2 (IL‐7 and IL‐4) stimulating cytokines were added; after 6‐day proliferation, IFN‐γ and IL‐5 secretions were determined. Without the addition of cytokines, consistent allergen‐induced proliferation was observed in PBMCs of nickel‐allergic patients only. By contrast, the addition of type 1 or type 2 stimulating cytokines resulted in a significantly enhanced allergen‐specific proliferation for all allergens tested (sensitivity increased from 26 to 43% or 38%, respectively,P < 0.05). In these cultures, allergen‐induced IFN‐γ and IL‐5 secretion was also significantly increased, compared to healthy controls (P < 0.05, for IFN‐γ sensitivity 79%, specificity 93%; for IL‐5 sensitivity 74%, specificity 81%). In conclusion, these results demonstrate an increased proliferative capacity and cytokine production by allergen‐specific T cells from allergic patients, but not of healthy individuals upon stimulation with allergens in combination with type 1 or 2 skewing cytokines. The present data warrant further exploration of the application of this test to a broader set of allergens.