bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser-scanning confocal vibrometer microscope: Theory and experiments
Authors: Rembe Christian , Dräbenstedt Alexander
Published: August 2006

In this article we present a new laser-scanning confocal microscope for vibration measurements in microscopic mechanical and biological structures. Our system can map out-of-plane vibrations with picometer amplitude resolution while the locus transverse and depth resolutions are in the submicrometer regime. We have achieved this performance by using the measurement beam of a heterodyne laser-Doppler vibrometer as the scanned laser beam of a confocal microscope. The power of the heterodyne carrier is a measurement of the detected light intensity. Therefore, the laser-scanning confocal laser-Doppler vibrometer microscope (CVM) can also be used as common confocal microscope to image and measure geometries of three-dimensional structures. The focus of this article is on the analysis of the transverse resolution, which cannot be adopted from other techniques. Our realized CVM allows vibration measurements up to 20MHz. The measured minimum 1∕e2-power spot diameter of 730nm enables vibration analysis of submicrometer structures. In this article we discuss the fundamental limits of this new microscope type and we demonstrate the results of our realized system.
Small-angle options of the upgraded ultrasmall-angle x-ray scattering beamline BW4 at HASYLAB
Authors: Roth S. V. , Döhrmann R. , Dommach M. , Kuhlmann M. , Kröger I. , Gehrke R. , Walter H. , Schroer C. , Lengeler B. , Müller-Buschbaum P.
Published: August 2006

We present the upgrade and present status of the ultrasmall-angle x-ray scattering (USAXS) beamline BW4 at the Hamburg Synchrotronstrahlungslabor. In order to extend the accessible scattering vector range, new small-angle setups have been established, making use of the high flux and small divergence of BW4. In standard transmission geometry using a beam size of B=400×400μm2 (horizontal×vertical), typical small-angle resolution ranges from dmax=90to650nm, depending on sample-to-detector distance. Additionally a new microfocus option has been established. This microfocus option allows reducing the sample size by one order of magnitude. Using parabolic beryllium compound refractive lenses, a new standard beam size of B=65×35μm2 (horizontal×vertical) can be provided. The μ-SAXS resolution is as high as dmax=150nm. Using μ-SAXS in combination with grazing incidence (μ-GISAXS) on a standard noble metal gradient multilayer, we prove the feasibility of μ-GISAXS experiments at a second generation source.
Relationship between thermodynamics and dynamics of supercooled liquids
Authors: Mittal Jeetain , Errington Jeffrey R. , Truskett Thomas M.
Published: August 2006

Diffusivity, a measure for how rapidly a fluid self-mixes, shows an intimate, but seemingly fragmented, connection to thermodynamics. On one hand, the “configurational” contribution to entropy (related to the number of mechanically stable configurations that fluid molecules can adopt) has long been considered key for predicting supercooled liquid dynamics near the glass transition. On the other hand, the excess entropy (relative to ideal gas) provides a robust scaling for the diffusivity of fluids above the freezing point. Here we provide, to our knowledge, the first evidence that excess entropy also captures how supercooling a fluid modifies its diffusivity, suggesting that dynamics, from ideal gas to glass, is related to a single, standard thermodynamic quantity.
Stability and phase separation in mixed self-assembled monolayers
Authors: Yaliraki S. N. , Longo Gabriel , Gale Ella , Szleifer I. , Ratner Mark A.
Published: August 2006

Recent single molecule experiments rely on the self-assembly of binary mixtures of molecules with very different properties in a stable monolayer, in order to probe the characteristics of the interspersed molecule of interest in a controlled environment. However, not all efforts at coassembly have been successful. To study systematically the behavior of such systems, we derive the free energy of multicomponent systems of rods with configurational degrees of freedom, localized on a surface, starting from a generalized van der Waals description. The molecular parameters are determined by geometrical factors of the molecules and by their pairwise van der Waals interactions computed using molecular mechanics. Applying the model to two experimental situations, we are able to use the stability analysis of the respective mixtures to explain why coassembly was successful in one set of experiments (carotene and alkanethiol) and not in another (benzenethiols and alkanethiol). We outline general guidelines for suitable choices of molecules to achieve coassembly.
Characterizing stress in ultrathin silicon wafers
Authors: Paul Indrajit , Majeed Bivragh , Razeeb Kafil M. , Barton John
Published: August 2006

The aim of this letter is to calculate the mechanical grinding induced bow and stress in ultrathin silicon wafers. The reverse leakage current of a p-n junction diode fabricated on a 4in. silicon wafer was measured for wafers thinned to various thicknesses. A correlation with the residual stress was obtained through band gap narrowing effect. The analytical results were compared with experimental bow measurements using a laser profiler. The bow in 50μm thick wafer was found to be less than 2mm using the current grinding process.
Binary eutectic clusters and glass formation in ideal glass-forming liquids
Authors: Lu Z. P. , Shen J. , Xing D. W. , Sun J. F. , Liu C. T.
Published: August 2006

In this letter, a physical concept of binary eutectic clusters in “ideal” glass-forming liquids is proposed based on the characteristics of most well-known bulk metallic glasses (BMGs). The authors approach also includes the treatment of binary eutectic clusters as basic units, which leads to the development of a simple but reliable method for designing BMGs more efficiently and effectively in these unique glass-forming liquids. As an example, bulk glass formers with superior glass-forming ability in the Zr–Ni–Cu–Al and Zr–Fe–Cu–Al systems were identified with the use of the strategy.
Model reaction studies on vanadium oxide nanostructures on Pd(111)
Authors: Kratzer M. , Surnev S. , Netzer F. P. , Winkler A.
Published: August 2006

Deuterium desorption and reaction between deuterium and oxygen to water has been studied on ultrathin vanadium oxide structures prepared on Pd(111). The palladium sample was part of a permeation source, thus enabling the supply of atomic deuterium to the sample surface via the bulk. Different vanadium oxide films have been prepared by e-beam evaporation in UHV under oxygen atmosphere. The structure of these films was determined using low energy electron diffraction and scanning tunneling microscopy. The mean translational energy of the desorption and reaction products has been measured with a time-of-flight spectrometer. The most stable phases for monolayer and submonolayer VOx are particular surface-V2O3 and VO phases at 523 and 700K, respectively. Thicker films grow in the form of bulk V2O3. The mean translational energy of the desorbing deuterium species corresponds in all cases to the thermalized value. Apparent deviations from this energy distribution could be attributed to different adsorption/desorption and/or accommodation behaviors of molecular deuterium from the gas phase on the individual vanadium oxide films. The water reaction product shows a slightly hyperthermal mean translational energy, suggesting that higher energetic permeating deuterium contributes with higher probability to the water formation.
High performance thin-film flip-chip InGaN–GaN light-emitting diodes
Authors: Shchekin O. B. , Epler J. E. , Trottier T. A. , Margalith T. , Steigerwald D. A. , Holcomb M. O. , Martin P. S. , Krames M. R.
Published: August 2006

Data are presented on the operation of thin-film flip-chip InGaN∕GaN multiple-quantum-well light-emitting diodes (LEDs). The combination of thin-film LED concept with flip-chip technology is shown to provide surface brightness and flux output advantages over conventional flip-chip and vertical-injection thin-film LEDs. Performance characteristics of blue, white, and green thin-film flip-chip 1×1mm2 LEDs are described. Blue (∼441nm) thin-film flip-chip LEDs are demonstrated with radiance of 191mW∕mm2sr at 1A drive, more than two times brighter than conventional flip-chip LEDs. An encapsulated thin-film flip-chip blue LED lamp is shown to have external quantum efficiency of 38% at forward current of 350mA. A white lamp based on a YAG:Ce phosphor coated device exhibits luminous efficacy of 60lm∕W at 350mA with peak efficiency of 96lm∕W at 20mA and luminance of 38Mcd∕m2 at 1A drive current. Green (∼517nm) devices exhibit luminance of 37Mcd∕m2 at 1A.
Localized charge trapping due to adsorption in nanotube field-effect transistor and its field-mediated transport
Authors: Lin H. , Tiwari S.
Published: August 2006

Ambient adsorption is known to cause hysteretic behavior and irreproducible transport phenomena in carbon nanotubes and their corresponding field-effect transistors. The authors report that pulsed measurements, with a time constant below 500μs, provide reproducible characteristics of carbon nanotube field-effect transistor with minimal hysteresis. Transient measurements of fabricated devices in air reveal multiple time constants whose origins are linked to adsorption processes and the local electric field environment of the carbon nanotube surface. Additional measurements in vacuum allow them to further elaborate on distinct effects on device transport characteristics due to adsorption.
Self-synchronization in distributed Josephson junction arrays studied using harmonic analysis and power balance
Authors: Hassel J. , Grönberg L. , Helistö P. , Seppä H.
Published: August 2006

Power generation and synchronization in Josephson junction arrays have attracted attention for a long time stemming both from fundamental interest and from application potential. The authors study the array of junctions coupled to a distributed transmission line either driven by an external microwave signal or in a self-oscillating mode. The authors simplify the theoretical treatment in terms of harmonic analysis and power balance. The model explains large operation margins of superconductor-normal-superconductor and superconductor-insulator-normal-insulator-superconductor junction arrays. The authors also compare theory, experiments, and simulations of self-oscillating externally shunted superconductor-insulator-superconductor junction arrays.
Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects
Authors: Kupers Ron , Fumal Arnaud , de Noordhout Alain Maertens , Gjedde Albert , Schoenen Jean , Ptito Maurice
Published: August 2006

After loss of a particular sensory channel, the deprived cortex can be activated by inputs from other sensory modalities. It is not known whether activation of the rewired cortex evokes subjective experiences characteristic of that cortex or consistent with the rerouted sensory information. In a previous study, blind subjects were trained to perform visual tasks with a tongue display unit, a sensory substitution device that translates visual displays into electrotactile tongue stimulation. This cross-modal sensory stimulation activated their visual cortices. We now extend this finding by using transcranial magnetic stimulation to examine the perceptual correlates of training-induced plastic responses. We find that blind subjects proficient with the use of the tongue display unit report somatopically organized tactile sensations that are referred to the tongue when transcranial magnetic stimulation is applied over the occipital cortex. No such sensations were evoked in trained, blindfolded, seeing control subjects who performed the sensory substitution task equally well. These data show that the perceptual correlate of activity in a given cortical area reflects the characteristics of its novel sensory input source.
Dynamic redox control of NF-κB through glutaredoxin-regulated S-glutathionylation of inhibitory κB kinase β
Authors: Reynaert Niki L. , van der Vliet Albert , Guala Amy S. , McGovern Toby , Hristova Milena , Pantano Cristen , Heintz Nicholas H. , Heim John , Ho Ye-Shih , Matthews Dwight E. , Wouters Emiel F. M. , Janssen-Heininger Yvonne M. W.
Published: August 2006

The transcription factor NF-κB, a central regulator of immunity, is subject to regulation by redox changes. We now report that cysteine-179 of the inhibitory κB kinase (IKK) β-subunit of the IKK signalosome is a central target for oxidative inactivation by means of S-glutathionylation. S-glutathionylation of IKK-β Cys-179 is reversed by glutaredoxin (GRX), which restores kinase activity. Conversely, GRX1 knockdown sensitizes cells to oxidative inactivation of IKK-β and dampens TNF-α-induced IKK and NF-κB activation. Primary tracheal epithelial cells from
Glrx1
-deficient mice display reduced NF-κB DNA binding, RelA nuclear translocation, and MIP-2 (macrophage inflammatory protein 2) and keratinocyte-derived chemokine production in response to LPS. Collectively, these findings demonstrate the physiological relevance of the S-glutathionylation–GRX redox module in controlling the magnitude of activation of the NF-κB pathway.
Molecular basis for the herbicide resistance of Roundup Ready crops
Authors: Funke Todd , Han Huijong , Healy-Fried Martha L. , Fischer Markus , Schönbrunn Ernst
Published: August 2006

The engineering of transgenic crops resistant to the broad-spectrum herbicide glyphosate has greatly improved agricultural efficiency worldwide. Glyphosate-based herbicides, such as Roundup, target the shikimate pathway enzyme 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase, the functionality of which is absolutely required for the survival of plants. Roundup Ready plants carry the gene coding for a glyphosate-insensitive form of this enzyme, obtained from
Agrobacterium
sp. strain CP4. Once incorporated into the plant genome, the gene product, CP4 EPSP synthase, confers crop resistance to glyphosate. Although widely used, the molecular basis for this glyphosate-resistance has remained obscure. We generated a synthetic gene coding for CP4 EPSP synthase and characterized the enzyme using kinetics and crystallography. The CP4 enzyme has unexpected kinetic and structural properties that render it unique among the known EPSP synthases. Glyphosate binds to the CP4 EPSP synthase in a condensed, noninhibitory conformation. Glyphosate sensitivity can be restored through a single-site mutation in the active site (Ala-100–Gly), allowing glyphosate to bind in its extended, inhibitory conformation.
Heat-shock transcription factor (HSF)-1 pathway required for
Caenorhabditis elegans
immunity
Authors: Singh Varsha , Aballay Alejandro
Published: August 2006

Innate immunity comprises physical barriers, pattern-recognition receptors, antimicrobial substances, phagocytosis, and fever. Here we report that increased temperature results in the activation of a conserved pathway involving the heat-shock (HS) transcription factor (HSF)-1 that enhances immunity in the invertebrate
Caenorhabditis elegans
. The HSF-1 defense response is independent of the p38 MAPK/PMK-1 pathway and requires a system of chaperones including small and 90-kDa inducible HS proteins. In addition, HSF-1 is needed for the effects of the DAF-2 insulin-like pathway in defense to pathogens, indicating that interacting pathways control stress response, aging, and immunity. The results also show that HSF-1 is required for
C. elegans
immunity against
Pseudomonas aeruginosa
,
Salmonella enterica
,
Yersinia pestis
, and
Enterococcus faecalis
, indicating that HSF-1 is part of a multipathogen defense pathway. Considering that several coinducers of HSF-1 are currently in clinical trials, this work opens the possibility that activation of HSF-1 could be used to boost immunity to treat infectious diseases and immunodeficiencies.
PEAPOD
regulates lamina size and curvature in
Arabidopsis
Authors: White Derek W. R.
Published: August 2006

Although a complex pattern of interspersed cell proliferation and cell differentiation is known to occur during leaf blade development in eudicot plants, the genetic mechanisms coordinating this growth are unclear. In
Arabidopsis
, deletion of the
PEAPOD
(
PPD
) locus increases leaf lamina size and results in dome-shaped rather than flat leaves. Siliques are also altered in shape because of extra lamina growth. The curvature of a Δ
ppd
leaf reflects the difference between excess growth of the lamina and a limitation to the extension capacity of its perimeter. Excess lamina growth in Δ
ppd
plants is due to a prolonged phase of dispersed meristematic cell (DMC) proliferation (for example, the meristemoid and procambium cells that form stomatal stem cells and vascular cells, respectively) during blade development. The
PPD
locus is composed of two homologous genes,
PPD1
and
PPD2
, which encode plant-specific putative DNA-binding proteins. Overexpression of
PPD
reduces lamina size by promoting the early arrest of DMC proliferation during leaf and silique development. Therefore, by regulating the arrest of DMC proliferation, the
PPD
genes coordinate tissue growth, modulate lamina size, and limit curvature of the leaf blade. I propose a revised model of leaf development with two cell-cycle arrest fronts progressing from the tip to the base: the known primary front, which determines arrest of general cell proliferation, followed by a secondary front that involves
PPD
and arrests DMC division.
A2A adenosine receptor protects tumors from antitumor T cells
Authors: Ohta Akio , Gorelik Elieser , Prasad Simon J. , Ronchese Franca , Lukashev Dmitriy , Wong Michael K. K. , Huang Xiaojun , Caldwell Sheila , Liu Kebin , Smith Patrick , Chen Jiang-Fan , Jackson Edwin K. , Apasov Sergey , Abrams Scott , Sitkovsky Michail
Published: August 2006

The A2A adenosine receptor (A2AR) has been shown to be a critical and nonredundant negative regulator of immune cells in protecting normal tissues from inflammatory damage. We hypothesized that A2AR also protects cancerous tissues by inhibiting incoming antitumor T lymphocytes. Here we confirm this hypothesis by showing that genetic deletion of A2AR in the host resulted in rejection of established immunogenic tumors in ≈60% of A2AR-deficient mice with no rejection observed in control WT mice. The use of antagonists, including caffeine, or targeting the A2 receptors by siRNA pretreatment of T cells improved the inhibition of tumor growth, destruction of metastases, and prevention of neovascularization by antitumor T cells. The data suggest that effects of A2AR are T cell autonomous. The inhibition of antitumor T cells via their A2AR in the adenosine-rich tumor microenvironment may explain the paradoxical coexistence of tumors and antitumor immune cells in some cancer patients (the “Hellstrom paradox”). We propose to target the hypoxia→adenosine→A2AR pathway as a cancer immunotherapy strategy to prevent the inhibition of antitumor T cells in the tumor microenvironment. The same strategy may prevent the premature termination of immune response and improve the vaccine-induced development of antitumor and antiviral T cells. The observations of autoimmunity during melanoma rejection in A2AR-deficient mice suggest that A2AR in T cells is also important in preventing autoimmunity. Thus, although using the hypoxia→adenosine→A2AR pathway inhibitors may improve antitumor immunity, the recruitment of this pathway by selective drugs is expected to attenuate the autoimmune tissue damage.
The role of hydrophobic interactions in initiation and propagation of protein folding
Authors: Dyson H. Jane , Wright Peter E. , Scheraga Harold A.
Published: August 2006

Globular proteins fold by minimizing the nonpolar surface that is exposed to water, while simultaneously providing hydrogen-bonding interactions for buried backbone groups, usually in the form of secondary structures such as α-helices, β-sheets, and tight turns. A primary thermodynamic driving force for the formation of globular structure is thus the sequestration of nonpolar groups, but the correlation between the parts of proteins that are observed to fold first (termed folding initiation sites) and the “hydrophobicity” (as customarily defined) of the amino acids in these regions has been quite weak. It has previously been noted that many amino acid side chains contain considerable nonpolar sections, even if they also contain polar or charged groups. For example, a lysine side chain contains four methylenes, which may undergo hydrophobic interactions if the charged ε-NH
3
+
group is salt-bridged or hydrogen-bonded. Folding initiation sites might therefore contain not only accepted “hydrophobic” amino acids, but also larger charged side chains. Recent experiments on the folding of mutant apomyoglobins provides corroboration for models based on the hypothesis that folding initiation sites arise from hydrophobic interactions. A near-perfect correlation was observed between the areas of the molecule that are present in the burst-phase kinetic intermediate and both the free energy of formation of hydrophobic initiation sites and the parameter “average area buried upon folding,” which pinpoints large side chains, even those containing charged or polar portions. These results provide a putative mechanism for the control of protein-folding initiation and growth by polar/nonpolar sequence propensity alone.
Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: Role of the BMP-4 gene
Authors: Bowers Robert R. , Kim Jae Woo , Otto Tamara C. , Lane M. Daniel
Published: August 2006

Previous studies showed that exposure of C3H10T1/2 stem cells to bone morphogenetic protein-4 (BMP-4) produced cells that convert into adipocytes at high frequency when treated with differentiation inducers. In the present investigation, an independent approach shows that BMP-4 is required for stable commitment of pluripotent stem cells to the adipocyte lineage. Exposure of proliferating 10T1/2 stem cells to 5-azacytidine, a potent DNA methylation inhibitor, gave rise to a subpopulation of cells that can be cloned and that have the capacity to undergo conversion into adipocytes upon treatment with terminal differentiation inducers. Detailed studies performed with a cloned committed subline, the A33 line, verified stable adipocyte lineage determination in the absence of exogenous BMP-4. Remarkably, this cell line expresses and secretes BMP-4 during proliferation in the same time window that exogenous BMP-4 must be added to naïve 10T1/2 cells to induce maximal adipocyte commitment. Furthermore, exposure of A33 cells to noggin, a naturally occurring BMP-4–binding antagonist, during this critical time window blocks subsequent differentiation. The role of BMP-4 in adipocyte lineage commitment is further strengthened by gene expression profiling of proliferating 10T1/2 stem cells and A33 preadipocytes. These findings revealed changes in the molecular circuitry, specifically coordinated changes in the expression of members of the BMP-4 signaling pathway, that distinguish A33 preadipocytes from uncommitted parental 10T1/2 stem cells. Together, these studies provide compelling evidence for the participation of BMP-4 in adipocyte lineage determination.
Electro‐Acupuncture in Relieving Labor Pain
Authors: Qu Fan , Zhou Jue
Published: August 2006

To study the efficacy of electro‐acupuncture for the relief of labor pain, and to build a better understanding of how electro‐acupuncture might influence the neuroendocrine system, 36 primiparas were randomly divided into an electro‐acupuncture group and a control group. Assessments of pain intensity and degree of relaxation during labor were analyzed. The differences between the electro‐acupuncture group and the control group on the concentration of β‐endorphin (β‐EP) and 5‐hydroxytryptamine (5‐HT) in the peripheral blood were compared. The electro‐acupuncture group was found to exhibit a lower pain intensity and a better degree of relaxation than the control group (p = 0.018; p = 0.031). There existed a significant difference in the concentration of β‐EP and 5‐HT in the peripheral blood between the two groups at the end of the first stage (p = 0.037; p = 0.030). Electro‐acupuncture was found to be an effective alternative or complementary therapy in the relief of pain during labor. The benefit of electro‐acupuncture for relieving labor pain may be based on the mechanism of producing a synergism of the central nervous system (CNS) with a direct impact on the uterus through increasing the release of β‐EP and 5‐HT into the peripheral blood.
What Works in Strategic Partnerships for Children: a Research Review
Authors: Percy‐Smith Janie
Published: August 2006

Strategic partnerships have a key role to play in delivering the government's ‘Every Child Matters’ agenda. There is a developing body of research and other evidence and practice‐informed literature about what works in relation to partnership working. Drawing on a research review commissioned by Barnardos on strategic partnership working for children, this study summarises research findings from a number of sectors relating to the development, delivery and review of effective partnerships. Although there is widespread consensus within the research on the factors contributing to effective partnership processes, there is, currently, relatively little evidence that partnerships lead to positive outcomes for children and young people. © 2006 The Author(s). Journal compilation © National Children's Bureau.
Hormonal change and cytokine mRNA expression in peripheral blood mononuclear cells during the development of canine autoimmune thyroiditis
Authors: Choi E-W , Shin I-S , Bhang D-H , Lee D-H , Bae B-K , Kang M-S , Kim D-Y , Hwang C-Y , Lee C-W , Youn H-Y
Published: August 2006

To elucidate the hormonal change and alteration in cytokine expression in peripheral blood mononuclear cells (PBMC) during the early stage of autoimmune thyroiditis, we have developed a canine model of this disease, in which normal dogs were immunized with bovine thyroglobulin (Tg) and/or canine thyroid extract. Serum samples were collected weekly, anti-canine Tg antibody was measured by enzyme-linked immunosorbent assay (ELISA) and thyroid stimulating hormone (TSH) and total T4 levels by radioimmunoassay. We also assayed T lymphocyte proliferation in response to Tg, as well as measuring cytokine mRNA by semiquantitative reverse transcription–polymerase chain reaction (RT–PCR). All six dogs immunized with bovine Tg had both canine Tg autoantibody and anti-T4 antibody. When the sample from the highest TgAA titre time-point was compared with baseline the expression of mRNA encoding the Th1-type cytokine such as interferon (IFN)-γ, interleukin (IL)-18 and IL-15 was increased during the development of autoimmune thyroiditis. Expression of the Th2-type cytokine, IL-6 showed minimal change and IL-4 expression was not detected in any of the samples. Expression of the T suppressive cytokine, IL-10 and transforming growth factor (TGF)-β was increased in the presence of antigen stimulation. These findings suggest that, although autoimmune thyroiditis is an organ-specific autoimmune disease, systemic cytokine mRNA expression is also changed.
The impact on histopathology practice of new human tissue legislation in the UK
Authors: Underwood J C E
Published: August 2006

The undisclosed or unauthorized retention of tissue from autopsies in the UK and elsewhere has caused considerable public concern and much distress to some families. Histopathologists involved in these cases have also been discomfited. These events have exposed deficiencies in prevailing legislation, principally in the Human Tissue Act 1961 and the Coroners Rules 1984. New human tissue legislation comes into force in the UK in September 2006. The Human Tissue Act 2004 and the Human Tissue (Scotland) Act 2006 make it unlawful to remove, store and use tissue from the dead without appropriate authority. The Human Tissue Act 2004, which does not apply in Scotland, also prohibits the removal, storage and use of tissue from living individuals for purposes specified in the Act unless appropriate consent has been obtained. The Coroners (Amendment) Rules 2005, which came into force in June 2005, introduced new arrangements for dealing with the retention of tissue from bodies undergoing coroner's autopsies. This new legislative regime is intended to create a climate in which pathologists, patients and the public can have confidence that tissue is used appropriately and, when necessary, with proper authority or valid consent. However, other than in Scotland, there may be unintended consequences arising from restrictions on archiving, for audit and diagnostic review, tissue samples from coronial autopsies.
Histopathological characteristics of metastasizing squamous cell carcinoma of the skin and lips
Authors: Quaedvlieg P J F , Creytens D H K V , Epping G G , Peutz‐Kootstra C J , Nieman F H M , Thissen M R T M , Krekels G A
Published: August 2006

Aims:  The reported incidence of metastasis from squamous cell carcinoma (SCC) of the skin and lip varies between 0.5% and 16%. Clinical and histopathological criteria have been proposed to identify tumours that may have an increased risk of metastasis. The aim of this study was to define such high‐risk tumours, especially since the incidence of SCC of the skin is increasing.

Methods and results:  Histopathological features of metastasized skin and lip tumours and a matched group of non‐metastasizing tumours were reassessed. Characteristics studied were: tumour width, excision margins, histological subtype, Clark level, Breslow depth, tumour differentiation, inflammation, perineural and angio‐invasive growth, ulceration and desmoplasia. Data were statistically analysed separately for skin and labial lesions. Desmoplasia, Clark level, Breslow depth, maximum diameter, angio‐invasion, grading, perineural invasion, plasma cells and eosinophilic inflammatory response proved to be statistically significantly related to metastasis of skin tumours. Breslow depth, plasma cells and grading appeared to be statistically significantly related to metastasis of SCC of the lips.

Conclusions:  A typical metastatic SCC showed: a tumour width of at least 15 mm, a vertical tumour thickness (= Breslow) of at least 2 mm, less differentiation, presence of desmoplasia and an inflammatory response with eosinophils and plasma cells.
Apoptosis and extracellular matrix remodelling in human silicosis
Authors: Delgado L , Parra E R , Capelozzi V L
Published: August 2006

Aims:  Silicosis is a chronic occupational disease caused by the inhalation of free crystalline silica particles which produce inflammation and tissue destruction followed by remodelling of the extracellular matrix. Apoptosis has been implicated in the development of the initial inflammation that triggers the remodelling process. Our aim was to elucidate the importance of Fas‐ligand (Fas‐L) in this disorder and to study the relationship between Fas‐L and several other inflammatory and fibrotic remodelling markers.

Methods and results:  We analysed 23 lung biopsies from silicotic patients and five controls, quantifying Fas‐L and Bcl‐2 expression by inflammatory cells as well as mast cells and collagen and elastic fibres. We used immunohistochemistry and morphometry to evaluate the amount of Fas‐L and Bcl‐2. Our analysis revealed that the silicotic lung stage was significantly related to Fas‐L, mast cell and extracellular matrix remodelling. Fas‐L expression was inversely associated with mast cells, collagen/elastic deposition and the silicotic lung.

Conclusion:  Fas‐L, mast cell staining and collagen/elastic fibre quantities in silicotic lungs are strongly related to silicosis progression.
Diagnostic value of markers M2A, OCT3/4, AP‐2γ, PLAP and c‐KIT in the detection of extragonadal seminomas
Authors: Biermann K , Klingmüller D , Koch A , Pietsch T , Schorle H , Büttner R , Zhou H
Published: August 2006

Aims:  To compare the suitability of new seminoma markers including transcription factors AP‐2γ, OCT3/4 and M2A for detection of metastatic and extragonadal seminomas with the two well‐known markers c‐KIT and PLAP.

Materials and methods:  The immunohistochemical distribution of PLAP, c‐KIT, M2A, AP‐2γ and OCT3/4 was examined in two pineal germinomas, 28 metastatic seminomas and 10 of their testicular primaries. Evaluation of specificity was achieved by additional tissue array studies on 75 malignancies other than germ cell tumours (GCT). Clinical data including serum PLAP were available in 18 patients.

Results:  Compared with other markers, significantly better staining results were observed with antibodies to M2A and AP‐2γ in all seminomatous GCT. In contrast, the staining pattern with antibodies to c‐KIT, PLAP and OCT3/4 was variable or absent. The lowest specificity was obtained with c‐KIT, which was expressed in a variety of non‐GCT. The only M2A+ mesothelioma expressed no other seminoma markers. No correlation between serum PLAP level and tissue PLAP expression was found.

Conclusions:  M2A and AP‐2γ are the most sensitive markers for seminoma metastases or primary extragonadal seminomas. Combination of these markers provides highly specific and clear results for detection of a seminomatous GCT.
Nuclear maspin detection in renal cell tumours: possible diagnostic role and correlation with p53 status
Authors: Blandamura S , Giacomelli L , Leo G , Segato P , Ninfo V
Published: August 2006

Aim:  To investigate the presence of maspin in renal tumours in an attempt to improve our understanding of the underlying mechanism of renal carcinogenesis and for diagnostic purposes.

Methods and results:  We examined 122 renal neoplasms of varying histological types and immunohistochemically investigated maspin and p53 expression. All clear cell carcinomas (CC) were negative for maspin, whereas oncocytomas (OC), papillary renal cell carcinomas (PC), chromophobe carcinomas (CPC) and, at least focally, collecting duct carcinomas (CDC) stained positively. We found that p53 positivity had a statistically significant correlation with metastasis (P = 0.009) in CC and maspin showed a significant inverse correlation with the presence of metastasis in PC and CDC (P = 0.02).

Conclusions:  The detection of maspin may be useful for differential diagnostic purposes and suggests a different underlying mechanism in the development of the various histological types of renal carcinomas.
IGFII and MIB1 immunohistochemistry is helpful for the differentiation of benign from malignant adrenocortical tumours
Authors: Schmitt A , Saremaslani P , Schmid S , Rousson V , Montani M , Schmid D M , Heitz Ph U , Komminoth P , Perren A
Published: August 2006

Aims:  The differentiation of adrenocortical carcinomas from adenomas may be difficult based on morphology alone. Differential expression of insulin‐like growth factor (IGF) II and cyclin‐dependent kinase (CDK) 4 has recently been described in these tumours. The aim of this study was to investigate the diagnostic usefulness of these markers immunohistochemically.

Methods and results:  We examined 22 benign and 17 malignant adrenocortical tumours and compared IGFII and CDK4 expression with known immunohistochemical as well as morphological criteria of malignancy. Thirteen of 17 carcinomas showed immunohistochemical reactivity for IGFII, whereas all adenomas but one were negative. Intense CDK4 expression was detected in 11 of 17 carcinomas but was present in only three of 22 adenomas. The MIB1 index was > 5% in 14 of 16 carcinomas and was < 5% in all adenomas but one. The combination of IGFII immunohistochemistry with MIB1 index led to high sensitivity and specificity in detecting adrenocortical carcinomas.

Conclusions:  IGFII and MIB1 are helpful immunohistochemical markers to predict malignancy in adrenocortical neoplasms. These markers can be used in addition to clinical, gross and morphological features to establish a diagnosis in difficult cases.
Mechanisms of major histocompatibility complex class II‐restricted processing and presentation of the V antigen of Yersinia pestis
Authors: Shim Ho‐Ki , Musson Julie A. , Harper Helen M. , McNeill Hesta V. , Walker Nicola , Flick‐Smith Helen , Von Delwig Alexei , Williamson E. Diane , Robinson John H.
Published: August 2006

We mapped mouse CD4 T‐cell epitopes located in three structurally distinct regions of the V antigen of Yersinia pestis. T‐cell hybridomas specific for epitopes from each region were generated to study the mechanisms of processing and presentation of V antigen by bone‐marrow‐derived macrophages. All three epitopes required uptake and/or processing from V antigen as well as presentation to T cells by newly synthesized major histocompatibility complex (MHC) class II molecules over a time period of 3–4 hr. Sensitivity to inhibitors showed a dependence on low pH and cysteine, serine and metalloproteinase, but not aspartic proteinase, activity. The data indicate that immunodominant epitopes from all three structural regions of V antigen were presented preferentially by the classical MHC class II‐restricted presentation pathway. The requirement for processing by the co‐ordinated activity of several enzyme families is consistent with the buried location of the epitopes in each region of V antigen. Understanding the structure–function relationship of multiple immunodominant epitopes of candidate subunit vaccines is necessary to inform choice of adjuvants for vaccine delivery. In the case of V antigen, adjuvants designed to target it to lysosomes are likely to induce optimal responses to multiple protective T‐cell epitopes.
Historical biogeographical patterns of the species of Bursera (Burseraceae) and their taxonomic implications
Authors: Espinosa David , Llorente Jorge , Morrone Juan J.
Published: August 2006

Aim  The plant genus Bursera, with 104 species of trees and shrubs, has been used as a model for biogeographical analyses because of its high species richness and large number of endemic species. The biogeographical patterns of Bursera and their implications for its phylogenetic classification are reviewed in order that some hypotheses on the historical biogeography of tropical Mexico can be proposed.

Location  Bursera is found in the south‐western USA, most of Mexico, mainly below 1700 m elevation in tropical forests, with some species in xeric shrublands, diversifying along the Pacific slope, Central America, and north‐western South America. A few species occur on the Galapagos and Revillagigedo archipelagos, some of which are endemics, whereas in the Antilles species are distributed extensively, with several endemics in the Bahamas, Cuba, Jamaica, and Hispaniola.

Methods  Data from specimens in herbaria and the literature were used to construct a matrix of 104 species in 160 areas. Distributional patterns of the species of Bursera were inferred applying track analysis, parsimony analysis of endemicity (PAE), and Brooks parsimony analysis (BPA).

Results  Track analysis revealed four individual tracks: (1) a circum‐Caribbean track, comprising species of the Bursera simaruba species group; (2) an Antillean track, including species that have been transferred to Commiphora based on their pollen traits; (3) a Mexican Pacific track, including species of the B. fragilis, B. microphylla, and B. fagaroides species groups, called ‘cuajiotes’; and (4) a Neotropical Pacific track, including the two species groups assigned to section Bullockia, in which the individual track of the Bursera copallifera species group is nested within the track of the B. glabrifolia species group. The four tracks overlap in a node in the Mexican Pacific slope, where they are highly diversified. PAE allowed us to identify 22 areas of endemism: 12 in Mexico (11 along the Mexican Pacific slope), six in the Antilles, two in Central America, one in South America, and one in the Galapagos. The general area cladogram obtained by BPA has two main clades: one includes the greater Antilles; and the other, 12 Mexican areas of endemism.

Main conclusions  Bursera fragilis, B. microphylla, and B. fagaroides species groups can be treated together as a new section within Bursera, sect. Quaxiotea, because they are segregated from the other groups of sect. Bursera based on morphological, anatomical, molecular and geographical evidence.
Effects of hydroxyurea on malaria, parasite growth and adhesion in experimental models
Authors: PINO P. , TAOUFIQ Z. , BRUN M. , TEFIT M. , FRANETICH J. F. , CICERON L. , KRISHNAMOORTHY R. , MAZIER D.
Published: August 2006

We recently raised concern over using hydroxyurea (HU) in the treatment of sickle cell disease in areas endemic for malaria, becauseit up‐regulates the endothelial surface expression of ICAM‐1, a major receptor for Plasmodium falciparum‐infected erythrocytes in the brain. Using human in vitro models of cerebral malaria, we evaluated the interaction of HU with parasites and demonstrated that HU pretreatment increased the number of infected red blood cells adhering to the endothelium, but did not increase endothelial apoptosis. Moreover, using an experimental cerebral malaria model, HU pretreatment was found to prevent significantly mice from developing neurological syndrome by inhibiting parasite growth, opening potential therapeutic avenues.
Secondary syphilis after liver transplantation: case report and review of the literature
Authors: Wolf Sabine C. , Kempf Volkhard A.J. , Tannapfel Andrea , Petersen Peter , Risler Teut , Brehm Bernhard R.
Published: August 2006

Abstract:  Syphilitic disease is uncommon, but its incidence has increased worldwide in the last few years. An unusual manifestation of secondary syphilis after orthotopic liver transplantation is described which confirms that lues should be considered in patients with immune deficiency and abnormal liver function tests.
Remnant liver regeneration and spleen volume changes after living liver donation: influence of the middle hepatic vein
Authors: Chen Tai‐Yi , Chen Chao‐Long , Huang Tung‐Liang , Tsang Leo Leung‐Chit , Wang Chih‐Chi , Wang Shih‐Ho , Yang Chin‐Hsiang , Concejero Allan M , Cheng Yu‐Fan
Published: August 2006

Abstract: Background and objectives: Graft harvest with or without the middle hepatic vein (MHV) affects venous return and function of the remaining liver. The aims of this study are to compare the remnant liver volume and spleen changes in the donors of different types of graft harvest and to evaluate the influence of resection with or without the MHV on the remnant liver volume regeneration, spleen volume change and serum total bilirubin.

Patients and methods:A total of 165 donors were grouped according to the type of graft harvest: 88 donors underwent left lateral segmentectomy (LLS), 10 donors underwent extend LLS or left lobectomy (LL), and 67 donors underwent right lobectomy (RL). Groups LLS and LL were later combined as group LH (left hepatectomy, n = 98). There were 68 men and 97 women. The mean age was 32.9 ± 8.1 yr. The total liver volume (LV) and spleen volume (S1) before graft harvest, graft weight (GW), regenerated liver volume (LV6m) and spleen volume (S2) six months post‐donation were calculated.

Results: There were no significant differences in the regenerated liver volume six months postoperation (LV6m) and recovery ratio (LV6m/LV × 100%) among the different groups, albeit significant smaller LV6min both groups compared with the initial liver volume was noted. Postoperative spleen volume (S2), average spleen ratio (S2/S1) and spleen change ratio were significantly larger and higher in group RL than in group LH. A significant increase in spleen volume was noted in both groups six months after graft harvest. A significantly higher TB in group RL (4.1 ± 1.7 mg/dL, range: 1.4–8.5 mg/dL) was noted compared with that of group LH (1.6 ± 1.0 mg/dL, range: 0.7–6.2 mg/dL).

Conclusion:There was a significant increase in the regenerated remnant liver and splenic volumes six months postoperation in all types of hepatectomy following living donor hepatectomy, and there was no difference in the mean TB levels among donors whether the MHV was included or not in the graft.
The use of a micro‐bubble contrast agent to allow visualization of the biliary tree
Authors: Roberts John P. , Neill Anne , Goldstein Ruth
Published: August 2006

Abstract:  Micro‐bubble contrast agents have been used as contrast agents in the vascular system to allow visualization of blood flow by ultrasound. We examined the use of this type of contrast agent for visualization of bile duct by ultrasound. A laparotomy was performed on a domestic farm pig and the common bile duct was cannulated with a 20 gauge catheter. The contrast agent, perflutren lipid microspheres (Definity), was injected in different dilutions. Sonographic images were obtained by scanning directly on the pig liver. The use of the micro‐bubble contrast in the biliary system provided excellent visualization of the bile duct down to ducts as small as fifth‐order branches and demonstrated bile ducts <2 mm. The use of micro‐bubble contrast agents in the biliary tree may allow for real‐time imaging of the bile duct and could be helpful in living donor liver transplantation.
A systematic review of barriers in access to renal transplantation among African Americans in the United States
Authors: Navaneethan Sankar D. , Singh Sonal
Published: August 2006

Abstract:  Background:  African‐American patients with end‐stage renal disease are less likely than white patients to undergo renal transplantation. The development of strategies to address this disparity requires an evidence‐based understanding of the barriers that impede access to renal transplantation among African Americans in the United States.

Methods:  In September 2005, we searched MEDLINE, EMBASE, and CENTRAL for articles that identified the barriers that impeded African Americans’ access to renal transplantation. Two reviewers independently extracted relevant data from the included studies. Barriers were broadly divided under two categories: (i) patient‐related barriers; and (ii) healthcare‐related barriers.

Results:  We obtained 76 potentially relevant articles of which 11 studies were included in the final review. Several patient‐related barriers – personal and cultural beliefs about transplantation, lower socioeconomic status and levels of education, and healthcare‐related barriers – physician perception about survival of African Americans post‐transplantation, inadequate transplant work‐up despite being referred, and HLA‐mismatching were identified at different stages of the transplantation process. Personal and cultural beliefs of African‐American patients were consistently identified as patient‐related barriers among several studies. Physicians’ perception about post‐transplantation survival of African Americans was the most commonly identified healthcare‐related barrier.

Conclusions:  A wide spectrum of patient‐related barriers including their personal and cultural beliefs about transplantation and several healthcare‐related barriers at different stages of the transplant process impedes access to renal transplantation among African Americans in the United States. A multisectoral approach focusing on these barriers needs to be evaluated to reduce disparities in renal transplantation in the United States.