bluuebunny/crossref_metadata_2025 huggingface dataset:
Si nanowire growth and characterization using a microelectronics-compatible catalyst: PtSi
Authors: Baron T. , Gordon M. , Dhalluin F. , Ternon C. , Ferret P. , Gentile P.
Published: December 2006

Crystalline Si nanowires have been grown using a microelectronics-friendly solid-phase catalyst (PtSi) by chemical vapor deposition. Tapered growth occurs at high deposition temperatures (>700°C) due to uncatalyzed Si deposition at wire sidewalls, but this effect can be reduced at lower T (<600°C), while still maintaining reasonable growth rates (1μm∕h). Electrical testing of individual nanowires using conductive atomic force microscopy on as-grown samples demonstrates that wires are conducting with intrinsic resistivities in the 10–50Ωcm range.
The functional equation truncation method for approximating slow invariant manifolds: A rapid method for computing intrinsic low-dimensional manifolds
Authors: Roussel Marc R. , Tang Terry
Published: December 2006

A slow manifold is a low-dimensional invariant manifold to which trajectories nearby are rapidly attracted on the way to the equilibrium point. The exact computation of the slow manifold simplifies the model without sacrificing accuracy on the slow time scales of the system. The Maas-Pope intrinsic low-dimensional manifold (ILDM) [Combust. Flame 88, 239 (1992)] is frequently used as an approximation to the slow manifold. This approximation is based on a linearized analysis of the differential equations and thus neglects curvature. We present here an efficient way to calculate an approximation equivalent to the ILDM. Our method, called functional equation truncation (FET), first develops a hierarchy of functional equations involving higher derivatives which can then be truncated at second-derivative terms to explicitly neglect the curvature. We prove that the ILDM and FET-approximated (FETA) manifolds are identical for the one-dimensional slow manifold of any planar system. In higher-dimensional spaces, the ILDM and FETA manifolds agree to numerical accuracy almost everywhere. Solution of the FET equations is, however, expected to generally be faster than the ILDM method.
Time-related conversion of the carbon nanotube field effect transistor
Authors: Zhang Wenjing , Zhang Qifeng , Wu Jinlei
Published: December 2006

Multiwall carbon nanotube field effect transistors were fabricated by using Al contact electrodes. As time went by, the conversion of the device from n type to p type was observed, and the Schottky barrier for hole transport at the interface of Al/carbon nanotube decreased when the work function of the electrode increased. Experimental results support the opinion that the Fermi level of the metal moves from near the conduction band edge of the nanotube to the valence band edge. The result is attributed to the oxidation of Al electrodes. It is very helpful to understand the role of oxygen to improve the carbon the nanotube field effect transistor characteristics.
Toward laser emission of epitaxial nanorod arrays of ZnO grown by electrodeposition
Authors: Pauporté T. , Lincot D. , Viana B. , Pellé F.
Published: December 2006

Arrays of epitaxial, vertically oriented nanorods of ZnO are grown at low temperature (80°C) on the (0002) plane of GaN single crystals by electrodeposition in an aqueous solution. The freestanding nanocolumns are prepared by a template-free method based on simple solution chemistry. At room temperature, the nanorods present an amplified ultraviolet emission centered at 381nm with an excitation threshold at 4.4MWcm−2. The amplified emission of the ZnO columns is dominated by the radiative recombination of excitons.
Determination at 300K of the hole capture cross section of chromium-boron pairs in p-type silicon
Authors: Dubois S. , Palais O. , Ribeyron P. J.
Published: December 2006

Measurement of dissolved chromium concentration in p-type crystalline silicon by means of the change in carrier lifetime due to chromium-boron pair dissociation requires precise knowledge of the recombination parameters of dissolved chromium in silicon. This work, based on quasi-steady-state carrier lifetime measurements, aims to determine the value at 300K of the hole capture cross section of the chromium-boron pairs in p-type silicon, which is the only recombination parameter still unknown at this temperature. The complete knowledge of the recombination parameters allows the determination of dissolved chromium concentrations in p-type silicon as low as 1010cm−3, even when chromium atoms do not dominate carrier recombination.
Size-dependent strain effects in self-assembled CdSe quantum dots with Zn0.38Cd0.23Mg0.39Se barriers
Authors: Reparaz J. S. , Goñi A. R. , Alonso M. I. , Perez-Paz M. N. , Tamargo M. C.
Published: December 2006

From resonant Raman scattering measurements under hydrostatic pressure the authors were able to identify both the strain-shifted longitudinal optical phonon of CdSe quantum dots with different average size embedded in a quaternary ZnCdMgSe material and a Mg-local dot mode due to interdiffusion from the barrier. They show that the large tunability of the light emission, which covers most of the visible spectrum, is not only due to a different degree of confinement but also to a size-dependent built-in strain. The frequency of the Mg mode allowed them also to roughly estimate the amount of Mg interdiffusion into the quantum dots.
Single wall carbon nanotube double quantum dot
Authors: Jørgensen H. I. , Grove-Rasmussen K. , Hauptmann J. R. , Lindelof P. E.
Published: December 2006

The authors report on two top-gate defined, coupled quantum dots in a semiconducting single wall carbon nanotube, constituting a tunable double quantum dot system. The single wall carbon nanotubes are contacted by titanium electrodes and gated by three narrow top-gate electrodes as well as a back gate. The authors show that a bias spectroscopy plot on just one of the two quantum dots can be used to extract the addition energy of both quantum dots. Furthermore, honeycomb charge stability diagrams are analyzed by an electrostatic capacitor model that includes cross capacitances, and they extract the coupling energy of the double quantum dot.
Low threshold amplified spontaneous emission based on coumarin 151 encapsulated in mesoporous SBA-15
Authors: Zhang Dingke , Zhang Sumei , Ma Dongge , Gulimina  , Li Xiaotian
Published: December 2006

Amplified spontaneous emission (ASE) characteristics of a blue dye coumarin 151 encapsulated in a highly ordered mesoporous SBA-15 were studied. The spectra narrowing was observed and found that the threshold and loss were greatly reduced, and the gain is significantly increased compared with spin-coated coumarin 151 doped poly(4-vinylphenol) film. The ASE threshold, gain, and loss, respectively, reached 0.55mJpulse−1cm−2, 44.78cm−1, and 8.9cm−1 for the coumarin 151 encapsulated in mesoporous SBA-15 film. The optimized lasing action owes much to the effects of the better spatial confinement of the molecules in the ordered mesoporous structure of the host SBA-15.
Effect of nitrogen doping on optical properties and electronic structures of SrTiO3 films
Authors: Mi Y. Y. , Wang S. J. , Chai J. W. , Pan J. S. , Huan C. H. A. , Feng Y. P. , Ong C. K.
Published: December 2006

The nitrogen-doping induced changes in optical properties and electronic structures of SrTiO3 films have been investigated by using spectroscopic ellipsometry and x-ray photoemission spectroscopy. Combined with the first-principles calculations, it is found that the localized N 2p states above O 2p states are attributed to the new absorption edge at 500nm and the photoactivity in the visible light region. Our results are consistent with both recent experimental and theoretical studies on nitrogen-doped TiO2, where the visible light responses arise from the localized N 2p states slightly above the valence-band edge rather than the band gap narrowing.
Simultaneous determination of nonlinear optical and thermo-optic parameters of liquid samples
Authors: Santhi A. , Namboodiri Vinu V. , Radhakrishnan P. , Nampoori V. P. N.
Published: December 2006

The authors apply the theory of photothermal lens formation and also that of pure optical nonlinearity to account for the phase modulation in a beam as it traverses a nonlinear medium. It is used to simultaneously determine the nonlinear optical refraction and the thermo-optic coefficient. They demonstrate this technique using some metal phthalocyanines dissolved in dimethyl sulfoxide, irradiated by a Q-switched Nd:YAG laser with 10Hz repetition rate and a pulse width of 8ns. The mechanism for reverse saturable absorption in these materials is also discussed.
Dipole moments from atomic-number-dependent potentials in analytic density-functional theory
Authors: Dunlap Brett I. , Karna Shashi P. , Zope Rajendra R.
Published: December 2006

Molecular dipole moments of analytic density-functional theory are investigated. The effect of element-dependent exchange potentials on these moments are examined by comparison with conventional quantum-chemical methods and experiment for the subset of the extended G2 set of molecules that have nonzero dipole moment. Fitting the Kohn-Sham [Phys. Rev. 140, A1133 (1965)] potential itself makes a mean absolute error of less than 0.1D. Variation of α (Slater’s [Phys. Rev. 81, 385 (1951)] exchange parameter) values has far less effect on dipole moments than on energies. It is argued that in variable α methods one should choose the smaller of the two rather than the geometric mean of the two α values for the heteroatomic part of the linear-combination-atomic-orbital density. Calculations on the dipole moment of NH2(CH)24NO2 are consistent with earlier calculations and show that varying the differences between α values for atoms with different atomic numbers has only short-ranged electrostatic effects.
High power GaAs∕AlGaAs lasers (λ∼850nm) with ultranarrow vertical beam divergence
Authors: Karachinsky L. Ya. , Novikov I. I. , Shernyakov Yu. M. , Kuznetsov S. M. , Gordeev N. Yu. , Maximov M. V. , Kop’ev P. S. , Ben-Ami U. , Arbiv D. B. , Sharon A. , Kettler T. , Posilovic K. , Schulz O. , Shchukin V. A. , Pohl U. W. , Ledentsov N. N. , Bimberg D.
Published: December 2006

The authors study 850nm GaAs∕AlGaAs longitudinal photonic band crystal lasers with a vertical far field divergence of 9° (full width at half maximum). Differential quantum efficiency of 95% is achieved at a cavity length of 500μm. A total optical output power from broad area multimode devices was up to 6.3W and a maximum continuous wave single mode power from narrow stripe devices was 270mW.
Fire type mapping using object-based classification of Ikonos imagery
Authors: Mitri George H. , Gitas Ioannis Z.
Published: December 2006

Distinguishing and mapping areas of surface and crown fire spread has significant applications in the study of fire behaviour, fire suppression, and fire effects. Satellite remote sensing has supplied a suitable alternative to conventional techniques for mapping the extent of burned areas, as well as for providing post-fire related information (such as the type and severity of burn). The aim of the present study was to develop an object-based classification model for mapping the type of fire using very high spatial resolution imagery (Ikonos). The specific objectives were: (i) to distinguish between surface burn and canopy burn; and (ii) to assess the accuracy of the classification results by employing field survey data. The methodology involved two consecutive steps, namely image segmentation and image classification. First, image objects were extracted at different scales using multi-resolution segmentation procedures, and then both spectral and contextual object information was employed to classify the objects. The accuracy assessment revealed very promising results (approximately 87% overall accuracy with a Kappa Index of Agreement of 0.74). Classification accuracy was mainly affected by the density of the canopy. This could be attributed to the inability of the optical sensors to penetrate dense canopy to detect fire-affected areas. The main conclusion drawn in the present study is that object-oriented classification can be used to accurately distinguish and map areas of surface and crown fire spread, especially those occurring in open Mediterranean forests.
Forest floor fuel dynamics in mixed-oak forests of south-eastern Ohio
Authors: Graham John B. , McCarthy Brian C.
Published: December 2006

Silvicultural treatments alter fuel dynamics in forested systems, which may alter fire regime. Effects of thinning and prescribed fire on forest-floor fuels were studied in mixed-oak forests of south-eastern Ohio to examine fuel dynamics over time. Fuel characteristics were measured before, immediately after, and 3 years following fire and thinning treatments along 20-m transects (n = 432) following Brown’s planar intersect method. Measurements were taken to determine litter, duff, 1-h, 10-h, 100-h, and 1000-h sound (1000S) or rotten (1000R) fuel mass. Coarse woody debris (CWD) was sampled on 432 additional 80-m2 belt-transects. Repeated-measures analysis of variance with post-hoc Bonferonni comparisons was used to analyse the change in the fuels over time. The specific effects of silvicultural treatments varied over time with changes in larger, sound fuels (1000S and CWD) persisting longer than changes to finer (litter, duff, 1-h, 10-h, and 100-h) or less-sound (1000R) fuels, which appear to be more transient. Unlike in western North America where fuels accumulate over time, decomposition and productivity appear comparable in eastern mixed-oak forests. Aside from their impact on decomposition or productivity rates, silvicultural treatments appear to have little impact on fine-fuel loading in these systems.
Seasonality and fire severity in savanna landscapes of monsoonal northern Australia
Authors: Russell-Smith Jeremy , Edwards Andrew C.
Published: December 2006

Ten years of photo and associated data records from an extensive fire and vegetation effects monitoring programme established in two large north Australian National Parks were used to (1) develop a simple-to-use semiquantitative fire severity index based on observed fire impact on vegetation, particularly leaf-scorch height; and (2) explore relationships between seasonality and fire severity in different landform and vegetation types. Using a three-tiered fire severity scale, data for 719 fires recorded from 178 plots over the period 1995–2004 indicate that the great majority of early dry season (pre-August) fires were of very low severity (fire-line intensities <<1000 kW m–1), whereas fires later in the dry season were typically of substantially greater severity. Similar trends were evident for vegetation occupying all landform types. The utility and limitations of the fire severity index, and implications for ecologic, greenhouse inventory, and remote sensing applications are discussed.
A physical analogue of the Schelling model
Authors: Vinković Dejan , Kirman Alan
Published: December 2006

We present a mathematical link between Schelling‘s socio-economic model of segregation and the physics of clustering. We replace the economic concept of “utility” by the physics concept of a particle's internal energy. As a result cluster dynamics is driven by the “surface tension” force. The resultant segregated areas can be very large and can behave like spherical “liquid” droplets or as a collection of static clusters in “frozen” form. This model will hopefully provide a useful framework for studying many spatial economic phenomena that involve individuals making location choices as a function of the characteristics and choices of their neighbors.
Crystal structure of apo-calmodulin bound to the first two IQ motifs of myosin V reveals essential recognition features
Authors: Houdusse Anne , Gaucher Jean-François , Krementsova Elena , Mui Suet , Trybus Kathleen M. , Cohen Carolyn
Published: December 2006

A 2.5-Å resolution structure of calcium-free calmodulin (CaM) bound to the first two IQ motifs of the murine myosin V heavy chain reveals an unusual CaM conformation. The C-terminal lobe of each CaM adopts a semi-open conformation that grips the first part of the IQ motif (IQxxxR), whereas the N-terminal lobe adopts a closed conformation that interacts more weakly with the second part of the motif (GxxxR). Variable residues in the IQ motif play a critical role in determining the precise structure of the bound CaM, such that even the consensus residues of different motifs show unique interactions with CaM. This complex serves as a model for the lever arm region of many classes of unconventional myosins, as well as other IQ motif-containing proteins such as neuromodulin and IQGAPs.
Inhibition of MAPK stimulates the Ca
2+
-dependent big-conductance K channels in cortical collecting duct
Authors: Li Dimin , Wang Zhijian , Sun Peng , Jin Yan , Lin Dao-Hong , Hebert Steven C. , Giebisch Gerhard , Wang Wen-Hui
Published: December 2006

The kidney plays a key role in maintaining potassium (K) homeostasis. K excretion is determined by the balance between K secretion and absorption in distal tubule segments such as the connecting tubule and cortical collecting duct. K secretion takes place by K entering principal cells (PC) from blood side through Na
+
, K
+
-ATPase and being secreted into the lumen via both ROMK-like small-conductance K (SK) channels and Ca
2+
-activated big-conductance K (BK) channels. K reabsorption occurs by stimulation of apical K/H-ATPase and inhibition of K recycling across the apical membrane in intercalated cells (IC). The role of ROMK channels in K secretion is well documented. However, the importance of BK channels in mediating K secretion is incompletely understood. It has been shown that their activity increases with high tubule flow rate and augmented K intake. However, BK channels have a low open probability and are mainly located in IC, which lack appropriate transporters for effective K secretion. Here we demonstrate that inhibition of ERK and P38 MAPKs stimulates BK channels in both PC and IC in the cortical collecting duct and that changes in K intake modulate their activity. Under control conditions, BK channel activity in PC was low but increased significantly by inhibition of both ERK and P38. Blocking MAPKs also increased channel open probability of BK in IC and thereby it may affect K backflux and net K absorption Thus, modulation of ERK and P38 MAPK activity is involved in controlling net K secretion in the distal nephron.
Antigen Presenting Cells and Stromal Cells Trigger Human Natural Killer Lymphocytes to Autoreactivity: Evidence for the Involvement of Natural Cytotoxicity Receptors (NCR) and NKG2D
Authors: Poggi Alessandro , Zocchi Maria Raffaella
Published: December 2006

Human natural killer (NK) lymphocytes should not damage autologous cells due to the engagement of inhibitory receptor superfamily (IRS) members by HLA‐I. Nevertheless, NK cells kill self cells expressing low levels or lacking HLA‐I, as it may occur during viral infections (missing‐self hypothesis). Herein, we show that human NK cells can be activated upon binding with self antigen presenting cells or stromal cells despite the expression of HLA‐I. Indeed, NK cells can kill and produce pro‐inflammatory and regulating cytokines as IFN‐γ, TNF‐α and IL10 during interaction with autologous dendritic cells or bone marrow stromal cells or skin fibroblasts. The killing of antigen presenting and stromal cells is dependent on LFA1/ICAM1 interaction. Further, the natural cytotoxicity receptors (NCR) NKp30 and NKp46 are responsible for the delivery of lethal hit to DC, whereas NKG2D activating receptor, the ligand of the MHC‐related molecule MIC‐A and the UL16 binding protein, is involved in stromal cell killing. These findings indicate that different activating receptors are involved in cell to self cell interaction. Finally, NK cells can revert the veto effect of stromal cells on mixed lymphocyte reaction further supporting the idea that NK cells may alter the interaction between T lymphocytes and microenvironment leading to autoreactivity.
Towards a Coronavirus‐Based HIV Multigene Vaccine
Authors: Eriksson Klara K. , Makia Divine , Maier Reinhard , Ludewig Burkhard , Thiel Volker
Published: December 2006

Human immunodeficiency virus (HIV) infection represents one of the major health threats in the developing world. The costly treatment of infected individuals with multiple highly efficient anti‐HIV drugs is only affordable in industrialized countries. Thus, an efficient vaccination strategy is required to prevent the further spread of the infection. The molecular biology of coronaviruses and particular features of the human coronavirus 229E (HCoV 229E) indicate that HCoV 229E‐based vaccine vectors can become a new class of highly efficient vaccines. First, the receptor of HCoV 229E, human aminopeptidase N (hAPN or CD13) is expressed mainly on human dendritic cells (DCs) and macrophages indicating that targeting of HCoV 229E‐based vectors to professional antigen presenting cells can be achieved by receptor‐mediated transduction. Second, HCoV 229E structural genes can be replaced by multiple transcriptional units encoding various antigens. These virus‐like particles (VLPs) containing HCoV 229E‐based vector RNA have the ability to transduce human DCs and to mediate heterologous gene expression in these cells. Finally, coronavirus infections are associated with mainly respiratory and enteric diseases, and natural transmission of coronaviruses occurs via mucosal surfaces. In humans, HCoV 229E causes common cold by infecting the upper respiratory tract. HCoV 229E infections are mainly encountered in children and re‐infection occurs frequently in adults. It is thus most likely that pre‐existing immunity against HCoV 229E will not significantly impact on the vaccination efficiency if HCoV 229E‐based vectors are used in humans.
Safety and Efficacy of Vaccination Against Influenza in Patients With Rheumatoid Arthritis
Authors: Elkayam Ori
Published: December 2006

Vaccination against influenza is currently recommended for patients with rheumatoid arthritis (RA). The safety and efficacy of vaccination in patients suffering from rheumatic diseases is still a matter of debate. This review summarizes the studies performed on the safety and immunogenicity of influenza vaccination in patients with RA as well as the rheumatic complications of the vaccine in otherwise healthy persons. Several trials have shown that the vaccine induces an adequate humoral response and does not induce clinical exacerbation of RA. Rheumatic complications (mainly vasculitis) following influenza vaccination in the general population are scarce.
Apoptosis and Redistribution of the Ro Autoantigen in Balb/c Mouse Like in Subacute Cutaneous Lupus Erythematosus
Authors: Herrera-Esparza Rafael , Villalobos Ricardo , Bollain-y-Goytia Juan-Jose , Ramírez-Sandoval Roxana , Sánchez-Rodriguez Sergio H. , Pacheco-Tovar Guadalupe , Avalos-Diaz Esperanza
Published: December 2006

In subacute cutaneous lupus eryhematosus (SCLE) the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac‐DEVD‐CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5–30 mJ/cm2) equivalent to a moderate to severe sunburn. Animals were injected with monoclonal anti‐Ro antibodies from SCLE patients. Apoptosis was also induced by anti‐Fas antibody injection. Skin samples were examined by direct immunofluoresence, by TUNEL, and the expression of caspase 3 by RT‐PCR. Major findings of present studies were: 1. UVB irradiation and anti‐Fas induced apoptosis of keratinocytes. 2. Apoptosis redistribute the Ro antigen on cell surface and is better triggered by Ro antibody. 3. The caspase 3 inhibitor Ac‐DEVD‐CMK decreases the availability of Ro autoantigen in epidermis and prevents deposition of anti‐Ro. In conclusion, the caspase pathway would be blocked to avoid anti‐Ro deposition along skin; this finding would be a prospect in the treatment of SCLE patients.
Genetic Basis of Sjögren′s Syndrome. How Strong is the Evidence?
Authors: Anaya Juan-Manuel , Delgado-Vega Angélica María , Castiblanco John
Published: December 2006

Sjögren′s syndrome (SS) is a late‐onset chronic autoimmune disease (AID) affecting the exocrine glands, mainly the salivary and lachrymal. Genetic studies on twins with primary SS have not been performed, and only a few case reports describing twins have been published. The prevalence of primary SS in siblings has been estimated to be 0.09% while the reported general prevalence of the disease is approximately 0.1%. The observed aggregation of AIDs in families of patients with primary SS is nevertheless supportive for a genetic component in its etiology. In the absence of chromosomal regions identified by linkage studies, research has focused on candidate gene approaches (by biological plausibility) rather than on positional approaches. Ancestral haplotype 8.1 as well as TNF, IL10 and SSA1 loci have been consistently associated with the disease although they are not specific for SS. In this review, the genetic component of SS is discussed on the basis of three known observations: (a) age at onset and sex‐dependent presentation, (b) familial clustering of the disease, and (c) dissection of the genetic component. Since there is no strong evidence for a specific genetic component in SS, a large international and collaborative study would be suitable to assess the genetics of this disorder.
Mechanisms of Dyslipoproteinemias in Systemic Lupus Erythematosus
Authors: Borba Eduardo F. , Carvalho Jozelio F. , Bonfá Eloísa
Published: December 2006

Autoimmunity and inflammation are associated with marked changes in lipid and lipoprotein metabolism in SLE. Autoantibodies and cytokines are able to modulate lipoprotein lipase (LPL) activity, a key enzyme in lipid metabolism, with a consequent “lupus pattern” of dyslipoproteinemia characterized by elevated levels of very low‐density lipoprotein cholesterol (VLDL) and triglycerides (TG) and lower high‐density lipoprotein cholesterol (HDL) levels. This pattern favors an enhanced LDL oxidation with a subsequent deleterious foam cell formation. Autoantibodies and immunocomplexes may aggravate this oxidative injury by inducing accumulation and deposition of oxLDL in endothelial cells. Drugs and associated diseases usually magnify the close interaction of these factors and further promote the proatherogenic environment of this disease.
Promiscuous Gene Expression in the Thymus: The Root of Central Tolerance
Authors: Magalhães Danielle A. R. , Silveira Eduardo L. V. , Junta Cristina M. , Sandrin-Garcia Paula , Fachin Ana Lucia , Donadi Eduardo A. , Sakamoto-Hojo Elza T. , Passos Geraldo A. S.
Published: December 2006

The thymus is a complex organ with an epithelium formed by two main cell types, the cortical thymic epithelial (cTECs) and medullary thymic epithelial cells (mTECs), referred to as stroma. Immature thymocytes arising from the bone marrow, macrophages and dendritic cells also populate the thymus. Thymocytes evolve to mature T cells featuring cell differentiation antigens (CDs), which characterize the phenotypically distinct stages, defined as double‐negative (DN), double positive (DP) and single positive (SP), based on expression of the coreceptors CD4 and CD8. The thymus is therefore implicated in T cell differentiation and during development into T cells thymocytes are in close association with the stroma. Recent evidence showed that mTECs express a diverse set of genes coding for parenchymal organ specific proteins. This phenomenon has been termed promiscuous gene expression (PGE) and has led to the reconsideration of the role of the thymus in central T cell tolerance to self‐antigens, which prevents autoimmunity. The evidence of PGE is causing a reanalysis in the scope of central tolerance understanding. We summarize the evidence of PGE in the thymus, focusing particularly the use of cDNA microarray technology for the broad characterization of gene expression and demarcation of PGE emergence during thymus ontogeny.
NK Cells and Type 1 Diabetes
Authors: Rodacki Melanie , Milech Adolpho , de Oliveira José Egídio Paulo
Published: December 2006

Type 1 diabetes (T1D) is characterized by an immuno‐mediated progressive destruction of the pancreatic β cells. Due to the ability of NK cells to kill target cells as well as to interact with antigen‐presenting and T cells, it has been suggested that they could be involved in one or multiple steps of the immune‐mediated attack that leads to T1D. Abnormalities in the frequency and activity of NK cells have been described both in animal models and patients with T1D. Some of these alterations are linked to its onset while others seem to be a consequence of the disease. Here, we discuss the main characteristics of NK cells and review the studies that investigated the role of NK cells in T1D, both in mouse models and humans.
Quality of Life in Systemic Lupus Erythematosus
Authors: Panopalis Pantelis , Clarke Ann E.
Published: December 2006

Systemic lupus erythematosus (SLE) is a pervasive disease with wide‐ranging effects on physical, psychological and social well‐being. As such, a comprehensive assessment of SLE should include several different outcomes, such as quality of life (QoL) and economic costs, in addition to measures of disease activity and damage. In fact, disease effects on QoL are often considered of greater overall importance to patients. Two approaches have been used in the measurement of QoL: generic questionnaires and disease‐specific questionnaires. Generic questionnaires are designed to be used across various conditions and populations, whereas disease‐specific questionnaires are designed to measure outcomes in one specific disease or condition. The most commonly used measure of QoL is the Medical Outcomes Study Short Form 36 (SF‐36), which is a generic measure that is applicable in a variety of conditions, including SLE. Recently, SLE‐specific measures have been developed that may prove to be more responsive than generic measures. The hope is that improved outcome measures will allow for better assessment of SLE and eventually facilitate drug development and improve patient care.
Identification of Patients With Early Rheumatoid Arthritis: Challenges and Future Directions
Authors: Orozco Catalina , Olsen Nancy J.
Published: December 2006

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis that affects the adult population. Early diagnosis and treatment are the cornerstones to prevent joint damage and avoid long‐term costs and disability. This article reviews the limitations of the currently available tools for the evaluation of patients with early arthritis, including clinical assessment, serologic markers and imaging modalities. It also discusses gene expression analysis, a newer and potentially promising approach to the early diagnosis of RA.
The Wnt Signaling Antagonist Kremen1 is Required for Development of Thymic Architecture
Authors: Osada Masako , Ito Emi , Fermin Hector A. , Vazquez-Cintron Edwin , Venkatesh Tadmiri , Friedel Roland H. , Pezzano Mark
Published: December 2006

Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs). Kremen1 (Krm1) is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk) by competing for the lipoprotein receptor‐related protein (LRP)‐6 co‐receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2) stage and continuing until the CD4+CD8+(DP) stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1− / − mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5) Keratin 8+(K8) stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2‐fold increase in canonical Wnt signaling in TEC lines derived from krm1− / − mice, when compared with krm1+ / + derived TEC lines. Fluorescence activated cell sorting (FACS) analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1+EpCAM+) and medullary (UEA‐1+ EpCAMhi) epithelial subsets, within the krm1− / − thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1− / − mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.
Mel-18, a Polycomb Group Protein, Regulates Cell Proliferation and Senescence via Transcriptional Repression of Bmi-1 and c-Myc Oncoproteins
Authors: Guo Wei-Jian , Datta Sonal , Band Vimla , Dimri Goberdhan P.
Published: December 2006

Polycomb group (PcG) protein Bmi-1 is an important regulator of cell proliferation. It regulates cellular senescence and proliferation of cells via the transcriptional repression of INK4a/ARF locus and other target genes. Here, we report that Mel-18, a PcG ring finger protein (PCGF) transcriptionally down-regulates Bmi-1. Furthermore, the expression of Bmi-1 and Mel-18 inversely correlates in proliferating and senescent human fibroblasts. Bmi-1 down-regulation by Mel-18 results in accelerated senescence and shortening of the replicative life span in normal human cells. Importantly, using promoter-reporter, chromatin immunoprecipitation, and quantitative real-time primary transcript RT-PCR assays, and an RNA interference approach, we demonstrate that Bmi-1 is a bona fide target of c-Myc oncoprotein. Finally, our data suggest that Mel-18 regulates Bmi-1 expression during senescence via down-regulation of c-Myc. These studies link c-Myc and polycomb function in cell proliferation and senescence.
Regulation of Myosin II Dynamics by Phosphorylation and Dephosphorylation of Its Light Chain in Epithelial Cells
Authors: Watanabe Toshiyuki , Hosoya Hiroshi , Yonemura Shigenobu
Published: December 2006

Nonmuscle myosin II, an actin-based motor protein, plays an essential role in actin cytoskeleton organization and cellular motility. Although phosphorylation of its regulatory light chain (MRLC) is known to be involved in myosin II filament assembly and motor activity in vitro, it remains unclear exactly how MRLC phosphorylation regulates myosin II dynamics in vivo. We established clones of Madin Darby canine kidney II epithelial cells expressing MRLC-enhanced green fluorescent protein or its mutants. Time-lapse imaging revealed that both phosphorylation and dephosphorylation are required for proper dynamics of myosin II. Inhibitors affecting myosin phosphorylation and MRLC mutants indicated that monophosphorylation of MRLC is required and sufficient for maintenance of stress fibers. Diphosphorylated MRLC stabilized myosin II filaments and was distributed locally in regions of stress fibers where contraction occurs, suggesting that diphosphorylation is involved in the spatial regulation of myosin II assembly and contraction. We further found that myosin phosphatase or Zipper-interacting protein kinase localizes to stress fibers depending on the activity of myosin II ATPase.
msHOT: modifying Hudson's ms simulator to incorporate crossover and gene conversion hotspots
Authors: Hellenthal Garrett , Stephens Matthew
Published: December 2006

Summary: We have incorporated both crossover and gene conversion hotspots into an existing coalescent-based program for simulating genetic variation data for a sample of chromosomes from a population.

Availability: The source code for msHOT is available at , along with accompanying instructions.

Contact:  hellenth@stats.ox.ac.uk
ADP_EM: fast exhaustive multi-resolution docking for high-throughput coverage
Authors: Garzón José Ignacio , Kovacs Julio , Abagyan Ruben , Chacón Pablo
Published: December 2006

Motivation: Efficient fitting tools are needed to take advantage of a fast growth of atomic models of protein domains from crystallography or comparative modeling, and low-resolution density maps of larger molecular assemblies. Here, we report a novel fitting algorithm for the exhaustive and fast overlay of partial high-resolution models into a low-resolution density map. The method incorporates a fast rotational search based on spherical harmonics (SH) combined with a simple translational scanning.

Results: This novel combination makes it possible to accurately dock atomic structures into low-resolution electron-density maps in times ranging from seconds to a few minutes. The high-efficiency achieved with simulated and experimental test cases preserves the exhaustiveness needed in these heterogeneous-resolution merging tools. The results demonstrate its efficiency, robustness and high-throughput coverage.

Availability:  

Contact:  pablo@cib.csic.es

Supplementary information: Supplementary data are available at Bioinformatics online.
Protective Effect of Adhatoda vascia Nees against Radiation‐Induced Damage at Cellular, Biochemical and Chromosomal Levels in Swiss Albino Mice
Authors: Kumar Meenal , Samarth Ravindra , Kumar Madhu , Selvan Senthamil R. , Saharan Begraj , Kumar Ashok
Published: December 2006

Extract of Adhatoda vasica (L) Nees leaves has been used for treatment of various diseases and disorders in Ayurved and Unani medicine. Modulatory effect of ethanolic extract of A. vasica (L) Nees against radiation‐induced changes in terms of histological alterations in testis, reduced glutathione (GSH), lipid peroxidation (LPO), acid and alkaline phosphatases levels, and chromosomal alterations in Swiss albino mice was studied at various post‐irradiation intervals between 1 and 30 days. Mice exposed to 8 Gy radiation showed radiation‐induced sickness including marked changes in histology of testis and chromosomal aberrations in bone marrow cells with 100% mortality within 22 days. When ethanolic leaf extract of A. vasica was given orally at a dose of 800 mg kg−1 body weight per mouse for 15 consecutive days and then exposed to radiation, death of Adhatoda‐pretreated irradiated mice was reduced to 70% at 30 days. The radiation dose reduction factor was 1.43. There was significantly lesser degree of damage to testis tissue architecture and various cell populations including spermatogonia, spermatids and Leydig cells. Correspondingly, a significant decrease in the LPO and an increase in the GSH levels were observed in testis and liver of Adhatoda‐pretreated irradiated mice. Similarly, a significant decrease in level of acid phosphatase and increase in level of alkaline phosphatase were observed. Adhatoda pretreatment significantly prevented radiation‐induced chromosomal damage in bone marrow cells. The study suggests that Adhatoda plant extract has significant radioprotective effects on testis that warrants further mechanistic studies aimed at identifying the role of major ingredients in the extract.
Novel retrotransposon analysis reveals multiple mobility pathways dictated by hosts
Authors: Ichiyanagi Kenji , Nakajima Ryo , Kajikawa Masaki , Okada Norihiro
Published: December 2006

Autonomous non-long-terminal-repeat retrotransposons (NLRs) proliferate by retrotransposition via coordinated reactions of target DNA cleavage and reverse transcription by a mechanism called target-primed reverse transcription (TPRT). Whereas this mechanism guarantees the covalent attachment of the NLR and its target site at the 3′ junction, mechanisms for the joining at the 5′ junction have been conjectural. To better understand the retrotransposition pathways, we analyzed target–NLR junctions of zebrafish NLRs with a new method of identifying genomic copies that reside within other transposons, termed “target analysis of nested transposons” (TANT). Application of the TANT method revealed various features of the zebrafish NLR integrants; for example, half of the integrants carry extra nucleotides at the 5′ junction, which is in stark contrast to the major human NLR, LINE-1. Interestingly, in a cell culture assay, retrotransposition of the zebrafish NLR in heterologous human cells did not bear extra 5′ nucleotides, indicating that the choice of the 5′ joining pathway is affected by the host. Our results suggest that several pathways exist for NLR retrotransposition and argue in favor of host protein involvement. With genomic sequence information accumulating exponentially, our data demonstrate the general applicability of the TANT method for the analysis of a wide variety of retrotransposons.
Intra- and interpopulation genotype reconstruction from tagging SNPs
Authors: Paschou Peristera , Mahoney Michael W. , Javed Asif , Kidd Judith R. , Pakstis Andrew J. , Gu Sheng , Kidd Kenneth K. , Drineas Petros
Published: December 2006

The optimal method to be used for tSNP selection, the applicability of a reference LD map to unassayed populations, and the scalability of these methods to genome-wide analysis, all remain subjects of debate. We propose novel, scalable matrix algorithms that address these issues and we evaluate them on genotypic data from 38 populations and four genomic regions (248 SNPs typed for ∼2000 individuals). We also evaluate these algorithms on a second data set consisting of genotypes available from the HapMap database (1336 SNPs for four populations) over the same genomic regions. Furthermore, we test these methods in the setting of a real association study using a publicly available family data set. The algorithms we use for tSNP selection and unassayed SNP reconstruction do not require haplotype inference and they are, in principle, scalable even to genome-wide analysis. Moreover, they are greedy variants of recently developed matrix algorithms with provable performance guarantees. Using a small set of carefully selected tSNPs, we achieve very good reconstruction accuracy of “untyped” genotypes for most of the populations studied. Additionally, we demonstrate in a quantitative manner that the chosen tSNPs exhibit substantial transferability, both within and across different geographic regions. Finally, we show that reconstruction can be applied to retrieve significant SNP associations with disease, with important genotyping savings.
Synthetic biology projects in vitro
Authors: Forster Anthony C. , Church George M.
Published: December 2006

Advances in the in vitro synthesis and evolution of DNA, RNA, and polypeptides are accelerating the construction of biopolymers, pathways, and organisms with novel functions. Known functions are being integrated and debugged with the aim of synthesizing life-like systems. The goals are knowledge, tools, smart materials, and therapies.
Death potentially secondary to sub‐Tenon's block
Authors: Quantock C. L. , Goswami T.
Published: December 2006

An 82‐year‐old ASA 2 patient underwent routine sub‐Tenon's block for cataract surgery. One minute after injection of the local anaesthetic, the patient had a generalised tonic‐clonic seizure and developed refractory ventricular fibrillation; subsequent resuscitation was unsuccessful. With no evidence for intravascular injection, the lack of structural brain abnormalities, and the most striking feature on post mortem examination being severe triple vessel coronary artery disease, it was concluded that this was primarily cardiac in origin; however, the possibility of brainstem anaesthesia should also be considered.
Availability of comparative trials for the assessment of new medicines in the European Union at the moment of market authorization
Authors: Van Luijn Johan C. F. , Gribnau Frank W. J. , Leufkens Hubert G. M.
Published: December 2006

What is already known about this subject

• The assessment of the added therapeutic value of new medicines with a new active substance is hampered by the lack of appropriate comparative information.

• Though the extent of this information gap is generally perceived as substantial, it has not been quantified.

What this study adds

• Information from active controlled trials was available in less than half of the new medicines studied, constituting a significant hurdle for evidence‐based decisionmaking on the use of new medicines in initial years following market introduction.

Aims

To investigate the availability of information about premarketing randomized active‐control trials (RaCTs) involving medicines with a new active substance at the moment of market authorization in the European Union.

Methods

Information was obtained from the EMEA European Public Assessment Reports and the MEDLINE and EMBASE databases.

Results

Between 1999 and 2005, 48% of recently approved medicines (n = 122) had been studied in comparison with existing medicines at the moment of market authorization. About one‐third of these trials were published and publicly available at that moment.

Conclusions

For most new medicines evidence‐based assessment of the (added) therapeutic value is not really possible at the moment of market authorization.
Chronic constipation: advances in management
Authors: Wald A.
Published: December 2006

Abstract  Only a relatively small percentage of clinically constipated patients seek medical attention and most can be managed satisfactorily with conservative measures. This review mainly addresses those patients who have refractory or difficult‐to‐manage functional constipation who are referred to gastrointestinal specialists. Areas of review include insights into pathophysiology, the utility of diagnostic testing and the author's opinions concerning available pharmacologic agents, the role of behavioural therapies and the indications for surgical interventions in this heterogeneous group of patients.
Short hepatic vein reconstruction in biliary atresia patients with absent inferior vena cava
Authors: Dulundu Ender , Sugawara Yasuhiko , Kaneko Junichi , Kishi Yoji , Akamatsu Nobuhisa , Matsui Yuichi , Kokudo Norihiro , Makuuchi Masatoshi
Published: December 2006

Abstract:  Liver transplantation in patients with biliary atresia and polysplenia syndrome requires some technical adjustments. During eight yr, 75 biliary atresia patients underwent living donor liver transplantation. Of these, two patients were complicated by absent inferior vena cava with azygos continuation. Both patients received hemi‐liver grafts with short hepatic veins. Outflow was reconstructed using a cryopreserved vena cava. In both patients, the short hepatic vein was anastomosed to the vein graft end‐to‐end and the end of the vein graft was anastomosed with the common orifices of recipient's hepatic veins. Both of the patients survived the operation with satisfactory graft function. A hemi‐liver graft with short hepatic veins can be used for patients with biliary atresia with inferior vena cava agenesia using the current technique.