bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-sectional transmission electron microscopy method and studies of implant damage in single crystal diamond
Authors: Hickey D. P. , Kuryliw E. , Siebein K. , Jones K. S. , Chodelka R. , Elliman R.
Published: July 2006

Few transmission electron microscopy (TEM) studies of single crystal diamond have been reported, most likely due to the time and difficulty involved in sample preparation. A method is described for creating a TEM cross section of single crystal diamond using a focused ion beam and in situ lift-out. The method results in samples approximately 10μm long by 3μm deep with an average thickness of 100–300nm. The total time to prepare a cross-sectional TEM sample of diamond is less than 5h. The method also allows for additional thinning to facilitate high resolution TEM imaging, and can be applied to oddly shaped diamond samples. This sample preparation technique has been applied to the study of ion implantation damage in single crystal diamond and its evolution upon annealing. High-pressure–high-temperature diamonds were implanted with Si+ at an energy of 1MeV and a temperature of 30°C. One sample, with a (110) surface, was implanted with a dose of 1×1014Sicm−2 and annealed at 950°C for 10 and 40min. No significant defect formation or evolution was discernible by cross-sectional transmission electron microscopy. Another sample, with a (100) orientation, was implanted with 1MeV at 1×1015Sicm−2 and annealed at 1050°C for 10min. Prior to annealing, a heavily damaged but still crystalline region was observed. Upon annealing, the sample showed no signs of conversion either to an amorphous form of carbon or to graphite. This is unexpected as the energy and dose are above the previously reported graphitization threshold for diamond. Higher annealing temperatures and possibly a high vacuum will be required for future study of defect formation, evolution, and phase transformations in ion-implanted single crystal diamond.
Inhomogeneous rarefaction of the process gas in a direct current magnetron sputtering system
Authors: Jimenez F. , Ekpe S. D. , Dew S. K.
Published: July 2006

The interactions between energetic particles and the sputter gas in a magnetron sputtering system have strong effects on the growth, structures, and properties of the film. These interactions result in inhomogeneous rarefaction of the gas in the space between target and substrate and affect both the transport of particles towards the substrate and the dynamics of the plasma. A hybrid Monte Carlo and fluid model is developed to simulate three-dimensional (3D) gas rarefaction due to the sputtering of metals in argon, neon, and krypton. The governing equations are solved iteratively in a 3D space with a nonuniform grid (octree). Collision events between the sputtered particles and the process gas are assumed as the dominant source of gas heating; however, the effect of the reflected neutrals is also included in the model. Gas rarefaction profiles have been predicted for different process conditions. Model results compare well with experimental ones. The extent of rarefaction depends on process conditions as well as the thermal conductivity of the gas. Materials with high sputtering yield, such as silver, show more rarefaction at a given cathode current than those with low sputtering yield, such as tungsten and aluminum. A higher sputtering yield means more sputtered atoms, thus more energy and momentum deposited in the gas. For a 75mm target at 300W and 10mTorr, a rarefaction of about 65% is obtained for the sputtering of Al in Ar gas, with the substrate plane located 10cm in front of the target.
High efficiency SiO2–TiO2 hybrid sol-gel antireflective coating for infrared applications
Authors: Brinley E. , Seal S. , Folks R. , Braunstein E. , Kramer L. , Seal S.
Published: July 2006

Sol-gel derived antireflective thin films were created for chalcogenide glass substrates in the 1.5–5μm wavelength range of infrared region. Presented herein is a preparation and characterization of the hybrid sol-gel created including particle size, refractive index, pH, and Fourier transform infrared FTIR transmission spectra. It is shown that an increase of not less than 8% and up to 25.1% transmission is achieved using sol-gel derived antireflective coatings.
Formation of nickel silicide and germanosilicide layers on Si(001), relaxed SiGe∕Si(001), and strained Si/relaxed SiGe∕Si(001) and effect of postthermal annealing
Authors: Ko J. H. , Jang C. H. , Kim S. H. , Song Y.-J. , Lee N. E.
Published: July 2006

This study compared the formation of nickel silicide or germanosilicide layers on various SiGe based heterostructures as well as the effects of the different annealing schemes (one-step versus two-step annealing) on the morphological, structural, and electrical properties. Uniform nickel silicide or germanosilicide layers were first formed by rapid thermal annealing of various heterostructures. The two-step annealing process of the samples first at 400°C (TA1) and subsequently at between 600 and 800°C (TA2) led to an increase in the sheet resistance, which was attributed to the formation of a high-resistivity NiSi2 phase, the agglomeration of the silicide or germanosilicide layers, and the formation of an amorphous interlayer between the silicide or germanosilicide layers. The lower sheet resistance of the silicide or germanosilicide layers formed on the relaxed-Si1−xGex (x=0.15)∕Si(001) substrates by two-step annealing compared with that of the samples formed on the strained Si/relaxed SiGe∕Si(001) and Si(001) was attributed to the suppression of the high-resistivity NiSi2 phase as well as the superior thermal stability of the germanosilicide layer formed on the relaxed Si1−xGex (x=0.15)∕Si(001). The amorphous interlayers formed in the samples annealed using two-step procedure appeared to suppress interface roughening between the silicide or germanosilicide and the SiGe layer presumably due to the reduced Ni and Ge diffusion rate. Here, an amorphous interlayer was formed, which was attributed to the large negative heat of mixing in Ni–Si–Ge systems during the phase transformation and grain growth.
X-ray photoemission spectroscopy and Fourier transform infrared characterizations of C60 states in C60 doped conducting polymers
Authors: Kato H. , Takemura S. , Iwasaki K. , Watanabe Y. , Nanba N. , Hiramatsu T. , Nishikawa O. , Taniguchi M.
Published: July 2006

Conducting polymer polythiophene (PT) film incorporated with C60 was prepared by electrochemical doping and diffusing injection methods. Charge transfer and the molecule-chain interaction were investigated by x-ray photoemission spectroscopy (XPS). Vibration states of the doped C60 and polymer backbone in the hybrid films were also investigated by fourier transform infrared (FTIR) reflaction absorption spectroscopy and FTIR transmission. The XPS spectral profile of the electrochemically doped sample was different from that of the casting sample, which reflects the different dopant-chain interactions in polymer films. The higher binding peaks appearing in the C 1s spectra correspond to C60 and its charged states doped in the polymer, which are closely connected with threefold t1u lowest unoccupied molecular orbital and fivefold hu higest occupied molecular orbital. FTIR transmission measurements clarified that C60 molecules were doped in the polymer film using both electrochemical doping and casting, as characteristic peaks due to the vibration modes of C60 were observed. The C60 peaks observed in the spectra for electrochemical doping and casting samples differed, which reflects the different doping states of C60. The results of XPS and FTIR suggest the conductive state of PT may be controlled by changing the ionic states of C60.
Evolution of film temperature during magnetron sputtering
Authors: Shaginyan L. R. , Han J. G. , Shaginyan V. R. , Musil J.
Published: July 2006

We report on the results of measurements of the temperature TFsurf which developed on the surface of films deposited by magnetron sputtering of chromium and copper targets on cooling and non-cooling silicon substrates. The TFsurf and substrate temperature (Ts) were simultaneously measured using high-resolution IR camera and thermocouple, respectively. We revealed that the TFsurf steeply grows, keeps constant when it achieves saturation level, and rapidly drops to the value of the Ts after stopping the deposition. At the same time, the Ts either does not change for the case of cooling substrate or increases to a certain level for noncooling substrate. However, in both cases the Ts remains several times lower than the TFsurf. The TFsurf is proportional to the flux of energy delivered to the growth surface by sputtered atoms and other fast particles, weakly depends on the depositing metal and can achieve several hundreds of °C. This phenomenon is explained by a model assuming formation of a hot thin surface layer (HTSL) on the top of the growing film, which exists only during film deposition and exhibits extremely low thermal conductivity. Due to this unique property the temperature TFsurf of HTSL is several times higher than the Ts. Variations in the TFsurf fairly correlate with structure changes of Cr films along thickness investigated in detail previously.
Stress evolution as a function of substrate bias in rf magnetron sputtered yttria-stabilized zirconia films
Authors: Piascik Jeffrey R. , Thompson Jeffrey Y. , Bower Christopher A. , Stoner Brian R.
Published: July 2006

An increase in compressive stress was observed in rf magnetron sputtered yttria-stabilized zirconia thin films upon exposure to ambient conditions (25°C and 75% relative humidity). This increase was attributed to absorption of water molecules into intergranular pores. It was shown that increasing substrate bias power disrupted columnar grain growth and reduced the percent change in compressive stress when exposed to ambient environments. Transmission electron microscopy confirmed a reduction in intergranular porosity for substrate bias depositions but an increase in lateral defects. These defects are hypothesized to be stress-induced microcracks caused by a tetragonal to monoclinic phase transformation.
Integrated active transient thermography for rapid nondestructive analysis of sputtering target bond integrity
Authors: Wickersham C. E.
Published: July 2006

Integrated active transient thermography is described and used to evaluate bond integrity of sputtering targets. In integrated active transient thermography one surface of a bonded target-backing plate assembly is rapidly heated while an infrared camera captures the time dependence of the surface temperature distribution on the opposite side. Bond defects inhibit heat transfer between the backing plate and the target, causing a slower rate of surface temperature rise in areas with poor bond integrity. Finite element models of the heat flow in the target assembly are used to establish the expected temperature rise for a perfectly bonded target assembly. A bond integrity map that is independent of the target assembly geometry, analysis time, applied power, and material is obtained by dividing the difference between the integrated finite element model generated map and the integrated experimental bond integrity map by the integrated finite element map. Measurement time for a commercial sized sputtering target assembly is only 50s.
Extreme ultraviolet binary phase gratings: Fabrication and application to diffractive optics
Authors: Salmassi F. , Naulleau P. P. , Gullikson E. M. , Olynick D. L. , Liddle J. A.
Published: July 2006

Diffractive optics play an important role in a variety of fields such as astronomy, microscopy, and lithography. In the extreme ultraviolet region of the spectrum they have been difficult to make due to the extremely precise control required of their surface structure. We have developed a robust fabrication technique that achieves the required topographic control through the deposition of a thin film of Si on a Cr etch stop. We have fabricated binary phase gratings using this approach that have an efficiency of 80% of the theoretical maximum. This technique could be applicable to similar binary phase structures requiring precise topography control.
Effect of grain orientation on tantalum magnetron sputtering yield
Authors: Zhang Z. , Kho Ling , Wickersham C. E.
Published: July 2006

The differential sputter yields of tantalum grains during argon ion magnetron sputtering were measured and found to correlate with the atomic packing density in the uppermost atomic layer. Grains with their (110) planes aligned within 15° of the sputtering surface had the highest sputtering yield (0.95at./ion at 400eV). Simultaneously, grains oriented so that their (111) planes were within 15° of the sputtering surface had sputtering yields of around two times lower (0.47at./ion at 400eV). These results are consistent with the surface sputtering rather than the channeling model. A correlation was found between the number of free atoms on the surface as determined using a facetted surface model and the measured sputtering yield.
The Influence of a Sense of Time on Human Development
Authors: Carstensen Laura L.
Published: June 2006

The subjective sense of future time plays an essential role in human motivation. Gradually, time left becomes a better predictor than chronological age for a range of cognitive, emotional, and motivational variables. Socioemotional selectivity theory maintains that constraints on time horizons shift motivational priorities in such a way that the regulation of emotional states becomes more important than other types of goals. This motivational shift occurs with age but also appears in other contexts (for example, geographical relocations, illnesses, and war) that limit subjective future time.
MC1R
Germline Variants Confer Risk for
BRAF
-Mutant Melanoma
Authors: Landi Maria Teresa , Bauer Jürgen , Pfeiffer Ruth M. , Elder David E. , Hulley Benjamin , Minghetti Paola , Calista Donato , Kanetsky Peter A. , Pinkel Daniel , Bastian Boris C.
Published: June 2006

Germline variants in
MC1R
, the gene encoding the melanocortin-1 receptor, and sun exposure increase risk for melanoma in Caucasians. The majority of melanomas that occur on skin with little evidence of chronic sun-induced damage (non-CSD melanoma) have mutations in the
BRAF
oncogene, whereas in melanomas on skin with marked CSD (CSD melanoma) these mutations are less frequent. In two independent Caucasian populations, we show that
MC1R
variants are strongly associated with
BRAF
mutations in non-CSD melanomas. In this tumor subtype, the risk for melanoma associated with
MC1R
is due to an increase in risk of developing melanomas with
BRAF
mutations.
Lhx2 Maintains Stem Cell Character in Hair Follicles
Authors: Rhee Horace , Polak Lisa , Fuchs Elaine
Published: June 2006

During embryogenesis, stem cells are set aside to fuel the postnatal hair cycle and repair the epidermis after injury. To define how hair follicle stem cells are specified and maintained in an undifferentiated state, we developed a strategy to isolate and transcriptionally profile embryonic hair progenitors in mice. We identified Lhx2 as a transcription factor positioned downstream of signals necessary to specify hair follicle stem cells, but upstream from signals required to drive activated stem cells to terminally differentiate. Using gain- and loss-of-function studies, we uncovered a role for Lhx2 in maintaining the growth and undifferentiated properties of hair follicle progenitors.
Fishing Rights and Race Relations
Authors: Winter Nicholas J. G.
Published: June 2006

Prejudice in Politics
. Group Position, Public Opinion, and the Wisconsin Treaty Rights Dispute.
By Lawrence D. Bobo and Mia Tuan
. Harvard University Press, Cambridge, MA, 2006. 288 pp. $40, £25.95, €36.90. ISBN 0-674-01329-8.

Exploring how racial prejudice shapes the fate of political claims of a minority group, the authors discuss the controversy that surrounded the efforts of Wisconsin's Chippewa Indians to assert their traditional fishing and hunting rights.
Phosphate Starvation Induces the Sporulation Killing Factor of
Bacillus subtilis
Authors: Allenby Nicholas E. E. , Watts Carys A. , Homuth Georg , Prágai Zoltán , Wipat Anil , Ward Alan C. , Harwood Colin R.
Published: June 2006

Bacillus subtilis
produces and exports a peptide sporulation killing factor (SkfA) that induces lysis of sibling cells.
skfA
is part of the
skf
operon (
skfA-H
), which is responsible for immunity to SkfA, as well as for production and export of SkfA. Here we report that transcription of
skfA
is markedly induced when cells of
B. subtilis
are subjected to phosphate starvation. The role of PhoP in regulation of the
skf
operon was confirmed by in vitro gel shift assays, which showed that this operon is a new member of the PhoP regulon. A putative stem-loop structure in the
skfA-skfB
intergenic region is proposed to act as a stabilizer of an
skfA
-specific transcript.
Genetic Evidence for the Requirement of RecA Loading Activity in SOS Induction after UV Irradiation inEscherichia coli
Authors: Ivančić-Baće Ivana , Vlašić Ignacija , Salaj-Šmic Erika , Brčić-Kostić Krunoslav
Published: June 2006

The SOS response inEscherichia coliresults in the coordinately induced expression of more than 40 genes which occurs when cells are treated with DNA-damaging agents. This response is dependent on RecA (coprotease), LexA (repressor), and the presence of single-stranded DNA (ssDNA). A prerequisite for SOS induction is the formation of a RecA-ssDNA filament. Depending on the DNA substrate, the RecA-ssDNA filament is produced by either RecBCD, RecFOR, or a hybrid recombination mechansim with specific enzyme activities, including helicase, exonuclease, and RecA loading. In this study we examined the role of RecA loading activity in SOS induction after UV irradiation. We performed a genetic analysis of SOS induction in strains with a mutation which eliminates RecA loading activity in the RecBCD enzyme (recB1080allele). We found that RecA loading activity is essential for SOS induction. In therecB1080mutant RecQ helicase is not important, whereas RecJ nuclease slightly decreases SOS induction after UV irradiation. In addition, we found that therecB1080mutant exhibited constitutive expression of the SOS regulon. Surprisingly, this constitutive SOS expression was dependent on the RecJ protein but not on RecFOR, implying that there is a different mechanism of RecA loading for constitutive SOS expression.
Alanine Dehydrogenase Activity Is Required for Adequate Progression of Phycobilisome Degradation during Nitrogen Starvation in
Synechococcus elongatus
PCC 7942
Authors: Lahmi Roxane , Sendersky Eleonora , Perelman Alexander , Hagemann Martin , Forchhammer Karl , Schwarz Rakefet
Published: June 2006

Degradation of the cyanobacterial light-harvesting antenna, the phycobilisome, is a general acclimation response that is observed under various stress conditions. In this study we identified a novel mutant of
Synechococcus elongatus
PCC 7942 that exhibits impaired phycobilisome degradation specifically during nitrogen starvation, unlike previously described mutants, which exhibit aberrant degradation under nitrogen, sulfur, and phosphorus starvation conditions. The phenotype of the new mutant, AldΩ, results from inactivation of
ald
(encoding alanine dehydrogenase). AldΩ is deficient in transcription induction of a number of genes during nitrogen starvation. These genes include the “general nutrient stress-related” genes,
nblA
and
nblC
, the products of which are essential for phycobilisome degradation. Furthermore, transcripts of several specific nitrogen-responsive genes accumulate at lower levels in AldΩ than in the wild-type strain. In contrast,
ald
inactivation did not decrease the accumulation of transcripts during sulfur starvation. Transcription of
ald
is induced upon nitrogen starvation, which is consistent with the ability of wild-type cells to maintain a low cellular content of alanine under these conditions. Unlike wild-type cells, AldΩ accumulates alanine upon nitrogen starvation. Our analyses suggest that alanine dehydrogenase activity is necessary for an adequate cellular response to nitrogen starvation. Decomposition of alanine may be required to provide a sufficient amount of ammonia. Furthermore, the accumulated alanine, or a related metabolite, may interfere with the cues that modulate acclimation during nitrogen starvation. Taken together, our results provide novel information regarding cellular responses to nitrogen starvation and suggest that mechanisms related to nitrogen-specific responses are involved in modulation of a general acclimation process.
Regulation of LiaRS-Dependent Gene Expression inBacillus subtilis: Identification of Inhibitor Proteins, Regulator Binding Sites, and Target Genes of a Conserved Cell Envelope Stress-Sensing Two-Component System
Authors: Jordan Sina , Junker Anja , Helmann John D. , Mascher Thorsten
Published: June 2006

The regulatory network of the cell envelope stress response inBacillus subtilisinvolves both extracytoplasmic function σ-factors and two-component signal transducing systems. One such system, LiaRS, responds to cell wall antibiotics that interfere with the undecaprenol cycle and to perturbation of the cytoplasmic membrane. It is encoded by the last two genes of theliaIHGFSRlocus. Here, we analyzed the expression of two LiaR-dependent operons,liaIHGFSRandyhcYZ-yhdA, and characterized a palindromic sequence required for LiaR-dependent activation. Since induction of the strongliaIpromoter leads to bothliaIHandliaIHGFRStranscripts, LiaR is positively autoregulated. Systematic deletion analysis of theliaIoperon revealed that LiaF is a potent negative regulator of LiaR-dependent gene expression: a nonpolarliaFdeletion led to constitutive activation of both characterized LiaR-dependent promoters. TheliaFgene is conserved in both sequence and genomic context in theFirmicutesgroup of gram-positive bacteria, located directly upstream ofliaSRorthologs. LiaH, a homolog ofEscherichia coliphage shock protein A, also plays a more subtle role in negatively modulating the bacitracin-inducible expression from LiaR-dependent promoters. Our results support a model in which the LiaFRS module integrates both positive and negative feedback loops to transduce cell envelope stress signals.
GlpD and PlsB Participate in Persister Cell Formation in
Escherichia coli
Authors: Spoering Amy L. , Vulić Marin , Lewis Kim
Published: June 2006

Bacterial populations produce dormant persister cells that are resistant to killing by all antibiotics currently in use, a phenomenon known as multidrug tolerance (MDT). Persisters are phenotypic variants of the wild type and are largely responsible for MDT of biofilms and stationary populations. We recently showed that a
hipBA
toxin/antitoxin locus is part of the MDT mechanism in
Escherichia coli
. In an effort to find additional MDT genes, an
E. coli
expression library was selected for increased survival to ampicillin. A clone with increased persister production was isolated and was found to overexpress the gene for the conserved aerobic
sn
-glycerol-3-phosphate dehydrogenase GlpD. The GlpD overexpression strain showed increased tolerance to ampicillin and ofloxacin, while a strain with
glpD
deleted had a decreased level of persisters in the stationary state. This suggests that GlpD is a component of the MDT mechanism. Further genetic studies of mutants affected in pathways involved in
sn
-glycerol-3-phosphate metabolism have led to the identification of two additional multidrug tolerance loci,
glpABC
, the anaerobic
sn
-glycerol-3-phosphate dehydrogenase, and
plsB
, an
sn
-glycerol-3-phosphate acyltransferase.
Constitutive Activation of Two-Component Response Regulators: Characterization of VirG Activation inAgrobacterium tumefaciens
Authors: Gao Rong , Mukhopadhyay Aindrila , Fang Fang , Lynn David G.
Published: June 2006

Response regulators are the ultimate modulators in two-component signal transduction pathways. The N-terminal receiver domains generally accept phosphates from cognate histidine kinases to control output. VirG for example, the response regulator of the VirA/VirG two-component system inAgrobacterium tumefaciens, mediates the expression of virulence genes in response to plant host signals. Response regulators have a highly conserved structure and share a similar conformational activation upon phosphorylation, yet the sequence and structural features that determine or perturb the cooperative activation events are ill defined. Here we use VirG and the unique features of theAgrobacteriumsystem to extend our understanding of the response regulator activation. Two previously isolated constitutive VirG mutants, VirGN54D and VirGI77V/D52E, provide the foundation for our studies. In vivo phosphorylation patterns establish that VirGN54D is able to accumulate phosphates from small-molecule phosphate donors, such as acetyl phosphate, while the VirGI77V/D52E allele carries conformational changes mimicking the active conformation. Further structural alterations on these two alleles begin to reveal the changes necessary for response regulator activation.
Molecular Characterization of
Pantoea stewartii
subsp.
stewartii
HrpY, a Conserved Response Regulator of the Hrp Type III Secretion System, and its Interaction with the
hrpS
Promoter
Authors: Merighi Massimo , Majerczak Doris R. , Zianni Michael , Tessanne Kimberly , Coplin David L.
Published: June 2006

Pantoea stewartii
subsp.
stewartii
is a bacterial pathogen of corn. Its pathogenicity depends on the translocation of effector proteins into host cells by the Hrp type III secretion system. We previously showed by genetic analysis that the HrpX sensor kinase and the HrpY response regulator are at the head of a complex cascade of regulators controlling
hrp/hrc
secretion and
wts
effector genes. This cascade also includes the HrpS response regulator and the HrpL alternative sigma factor. These regulators are shared among many important plant pathogens in the genera
Pantoea
,
Erwinia
, and
Pseudomonas
. In this study, we dissect the regulatory elements in the
hrpS
promoter region, using genetic and biochemical approaches, and show how it integrates various environmental signals, only some of which are dependent on phosphorylation of HrpY. Primer extension located the transcriptional start site of
hrpS
at a σ
70
promoter 601 bp upstream of the open reading frame. Electrophoretic mobility shift assays and DNase I footprinting analysis demonstrated that HrpY binds to conserved regulatory elements immediately adjacent to this promoter, and its binding affinity was increased by phosphorylation at D57. A consensus sequence for the two direct repeats bound by HrpY is proposed. Deletion analysis of the promoter region revealed that both the HrpY binding site and additional sequences farther upstream, including a putative integration host factor binding site, are required for
hrpS
expression. This finding suggests that other unknown regulatory proteins may act cooperatively with HrpY.
Microvascular proliferation in congenital vascular malformations of skin and soft tissue
Authors: Meijer-Jorna Lorine B , van der Loos Chris M , de Boer Onno J , van der Horst Chantal M A M , van der Wal Allard C
Published: July 2006

Background:Congenital vascular malformations (VMs) are mass-forming lesions that usually progress slowly, but may become symptomatic because of episodes of sudden growth and pain, particularly those with a substantial component of arteriovenous shunting.

Aim:To systematically investigate the features of microvascular proliferation in a large series of surgically treated VMs.

Methods:107 resection specimens of clinically and histologically well-documented VMs were screened for the presence and extent of microvascular proliferation, based on morphological parameters, microvessel density (MVD), mast cell density (MCD) and proliferative activity (Ki-67 labelling index) of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). The extent of microvascular proliferation was correlated with the histological type of VM and clinical characteristics of patients.

Results:Microvascular proliferation was observed in 32 (30%) of all VMs, of which 30 cases seemed to be arteriovenous malformations. MVD in areas of microvascular proliferation was 282 (186)/mm2vs 13 (9)/mm2in areas with mature vessels. Both ECs and VSMCs in these areas showed high Ki-67 labelling indexes (mean (SD) 15 (18) and 17 (24)/mm2, respectively). In all lesions, a positive correlation was found between MCD and MVD. Age, sex and location of VM had no predictive value for the occurrence of microvascular proliferation. However, if present, the involved tissue areas were larger and the proliferative activity of EC was higher in male patients than in female patients.

Conclusions:Recognition of microvascular proliferation as a not uncommon feature, congenital arteriovenous malformations provide new insight into the growth behaviour and vascular composition of these lesions.
Endobronchial ultrasound-guided fine-needle aspiration and liquid-based thin-layer cytology
Authors: Wallace W A H , Monaghan H M , Salter D M , Gibbons M A , Skwarski K M
Published: July 2006

Background:Optimal management of patients with lung cancer requires accurate cell typing of tumours and staging at the time of diagnosis. Endobronchial ultrasound-guided lymph node aspiration as a method of diagnosing and staging lung cancer is a relatively new technique.

Aim:To report the use of liquid-based-thin-layer cytology for the processing and reporting of these specimens.

Methods:The specimens obtained from 80 patients were processed using the ThinPrep system, with the remainder of the samples being processed as a cell block.

Results:40 of the 81 procedures yielded malignant cells (30 non-small cell carcinoma, 8 small-cell carcinoma and 2 combined small-cell carcinoma/non-small-cell carcinoma). The cell blocks were found to contain sufficient material to allow the immunohistochemical characterisation of tumour cells with a range of antibodies.

Conclusion:The use of liquid-based-thin-layer cytological techniques provides high-quality specimens for diagnostic purposes. When used in conjunction with cell blocks, sufficient material may be obtained to allow immunohistochemical studies to confirm the tumour cell type. Given the current move towards centralisation of pathology services, this approach gives the pathologist high-quality specimens without the need for direct onsite support at the time of the procedure.
Improved clonality assessment in germinal centre/post-germinal centre non-Hodgkin’s lymphomas with high rates of somatic hypermutation
Authors: Catherwood Mark A , Gonzalez David , Patton Caroline , Dobbin Edwina , Venkatraman Lakshmi , Alexander H Denis
Published: July 2006

Background:PCR detects clonal rearrangements of the Ig gene in lymphoproliferative disorders. False negativity occurs in germinal centre/post-germinal centre lymphomas (GC/PGCLs) as they display a high rate of somatic hypermutation (SHM), which causes primer mismatching when detecting Ig rearrangements by PCR.

Aims:To investigate the degree of SHM in a group of GC/PGCLs and assess the rate of false negativity when using BIOMED-2 PCR when compared with previously published strategies.

Methods:DNA was isolated from snap-frozen tissue from 49 patients with GC/PGCL (23 diffuse large B cell lymphomas (DLBCLs), 26 follicular lymphomas (FLs)) and PCR-amplified for complete (VDJH), incomplete (DJH) and Igκ/λ rearrangements using the BIOMED-2 protocols, and compared with previously published methods using consensus primers. Germinal centre phenotype was defined by immunohistochemistry based on CD10, Bcl-6 and MUM-1.

Results:Clonality detection by amplifying Ig rearrangements using BIOMED-2 family-specific primers was considerably higher than that found using consensus primers (74% DLBCL and 96% FL vs 69% DLBCL and 73% FL). Addition of BIOMED-2 DJH rearrangements increased detection of clonality by 22% in DLBCL. SHM was present in VDJH rearrangements from all patients with DLBCL (median (range) 5.7% (2.5–13.5)) and FL (median (range) 5.3% (2.3–11.9)) with a clonal rearrangement.

Conclusions:Use of BIOMED-2 primers has significantly reduced the false negative rate associated with GC/PGCL when compared with consensus primers, and the inclusion of DJH rearrangements represents a potential complementary target for clonality assessment, as SHM is thought not to occur in these types of rearrangements.
Prognostic significance of mucins in colorectal cancer with different DNA mismatch-repair status
Authors: Lugli A , Zlobec I , Baker K , Minoo P , Tornillo L , Terracciano L , Jass J R
Published: July 2006

Background:Expression of mucin antigen MUC1 and down regulation of MUC2 are associated with adverse prognosis in colorectal cancer (CRC), but their prognostic significance with respect to differing DNA mis- match repair (MMR) status is poorly understood.

Objective:To determine the prognostic significance of MUC1 and MUC2 in CRC with different MMR statuses.

Methods:Using the tissue microarray (TMA) technique, a series of 1420 unselected, non-consecutive CRC resections was subdivided into three groups: (1) MMR-proficient; (2) MLH1-negative; and (3) presumed hereditary non-polyposis colon cancer (HNPCC). Immunohistochemical analysis of MUC1 and MUC2 expression (>0%) and loss (0%) was performed, and the results were correlated with clinicopathological parameters.

Results:In MMR-proficient CRC, MUC1 expression was more frequently found in tumours with higher tumour stage (p = 0.004) and higher tumour grade (p = 0.041) and loss of MUC2 was associated with higher tumour stage (p = 0.028), node stage (p = 0.001), presence of vascular invasion (p = 0.028) and worse survival (p = 0.034). In MLH1-negative CRC, MUC2 loss was associated with the presence of lymph node metastasis (p = 0.028) and worse survival (p = 0.015), but there was no association between MUC1 expression and clinicopathological features. In presumed HNPCC, MUC1 expression and MUC2 loss were not associated with clinicopathological parameters.

Conclusions:Mucins have a prognostic significance in sporadic CRC, but not in hereditary CRC. Loss of MUC2 is an adverse prognostic factor in MMR-proficient and MLH1-negative CRC, whereas MUC1 expression is associated with tumour progression in MMR-proficient CRC only.
Do French lay people and health professionals find it acceptable to breach confidentiality to protect a patient’s wife from a sexually transmitted disease?: Figure 1
Authors: Guedj M , Sastre M T Muñoz , Mullet E , Sorum P C
Published: June 2006

Objective:To determine under what conditions lay people and health professionals find it acceptable for a physician to breach confidentiality to protect the wife of a patient with a sexually transmitted disease (STD).

Methods:In a study in France, breaching confidentiality in 48 scenarios were accepted by 144 lay people, 10 psychologists and 7 physicians. The scenarios were all possible combinations of five factors: severity of the disease (severe, lethal); time taken to discuss this with (little time, much time); intent to inform the spouse about the disease (none, one of these days, immediately); intent to adopt protective behaviours (no intent, intent); and decision to consult an expert in STDs (yes, no), 2×2×3×2×2. The importance and interactions of each factor were determined, at the group level, by performing analyses of variance and constructing graphs.

Results:The concept of breaching confidentiality to protect a wife from her husband’s STD was favoured much more by lay people and psychologists than by physicians (mean ratings 11.76, 9.28 and 2.90, respectively, on a scale of 0–22). The patient’s stated intentions to protect his wife and to inform her of the disease had the greatest impact on acceptability. A cluster analysis showed groups of lay participants who found breaching confidentiality “always acceptable” (n = 14), “depending on the many circumstances” (n = 87), requiring “consultation with an expert” (n = 30) and “never acceptable (n = 13)”.

Conclusions:Most people in France are influenced by situational factors when deciding if a physician should breach confidentiality to protect the spouse of a patient infected with STD.
Privacy and patient–clergy access: perspectives of patients admitted to hospital
Authors: Erde E , Pomerantz S C , Saccocci M , Kramer-Feeley V , Cavalieri T A
Published: June 2006

Background:For patients admitted to hospital both pastoral care and privacy or confidentiality are important. Rules related to each have come into conflict recently in the US. Federal laws and other rules protect confidentiality in ways that countermand hospitals’ methods for facilitating access to pastoral care. This leads to conflicts and poses an unusual type of dilemma—one of conflicting values and rights. As interests are elements necessary for establishing rights, it is important to explore patients’ interests in privacy compared with their desire for attention from a cleric.

Aim:To assess the willingness of patients to have their names and rooms included on a list by religion, having that information given to clergy without their consent, their sense of privacy violation if that were done and their views about patients’ privacy rights.

Methods and participants:179 patients, aged 18–92 years, admitted to hospital in an acute care setting, were interviewed and asked about their preferences for confidentiality and pastoral support.

Results:Most (57%) patients did not want to be listed by religion; 58% did not think hospitals should give lists to clergy without their consent and 84% welcomed a visit by their own clergy even if triggered from a hospital list.

Conclusions:Values related to confidentiality or privacy and pastoral care were found to be inconsistent and more complicated than expected. Balancing the right to privacy and the value of religious support continue to present a challenge for hospitals. Patients’ preferences support the importance of providing balance in a way that protects rights while offering comprehensive services.
Authorship of research papers: ethical and professional issues for short-term researchers
Authors: Newman A , Jones R
Published: June 2006

Although the International Committee of Medical Journal Editors has published clear guidance on the authorship of scientific papers, short-term contract research workers, who perform much of the research that is reported in the biomedical literature, are often at a disadvantage in terms of recognition, reward and career progression. This article identifies several professional, ethical and operational issues associated with the assignment of authorship, describes how a university department of primary care set about identifying and responding to the concerns of its contract research staff on authorship and describes a set of guidelines that were produced to deal with the ethical and professional issues raised. These guidelines include directions on how authorship should be negotiated and allocated and how short-term researchers can begin to develop as authors. They also deal with the structures required to support an equitable system, which deals with the needs of short-term researchers in ways that are realistic in the increasingly competitive world of research funding and publication, and may offer a model for more formal guidelines that could form part of institutional research policy.
Rural and non-rural differences in membership of the American Society of Bioethics and Humanities: Table 1
Authors: Nelson William , Weeks William B
Published: June 2006

Objective:To determine whether bioethicists are distributed along a rural-to-urban continuum in a way that reflects potential need of those resources as determined by the general population, hospital facilities and hospital beds.

Methods:US members of a large, multidisciplinary professional society, the American Society of Bioethics and Humanities (ASBH), the US population, hospital facilities and hospital beds were classified across a four-tier rural-to-urban continuum. The proportion of each group in rural settings was compared with that in urban settings, and odds ratios were calculated with 95% confidence intervals.

Results:Although 91% of ASBH members live or work in urban settings, only 66% of the US population did so. In contrast, 2% of ASBH members live or work in rural settings compared with 13% of the population. ASBH members were 10.7 times (95% CI 6.6 to 17.3) as likely to be represented in urban than in rural settings when compared with the general population, 25.6 times (95% CI 15.8 to 41.5) and 6.9 times (95% CI 4.3 to 11.1) as likely with regard to hospital facilities and hospital beds, respectively.

Conclusions:Using various comparisons it was found that ASBH members are under-represented in rural as compared with urban settings. Although not all bioethicists are ASBH members, these findings suggest that the availability of professional bioethical resources may be inadequate in rural America. The disparities that were found may have considerable effect on ethics scholarship, research, ethical committees and education, and adds to the argument that rural American communities are under-served.
Non-commercial clinical trials of a medicinal product: can they survive the current process of research approvals in the UK?: Table 1
Authors: Sheard L , Tompkins C N E , Wright N M J , Adams C E
Published: June 2006

Over recent years, considerable attention has been paid to the National Health Service (NHS) research governance and ethics approvals process in the UK. New regulations mean that approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) is now also needed for conducting all clinical trials. Practical experience of gaining MHRA and sponsorship approval has yet to be described and critically explored in the literature. Our experience, from start to finish, of applying for these four approvals for a multicentre randomised controlled trial of two licensed drugs for opiate detoxification in the prison setting is described here. In addition, the implications of the approvals process for research projects, particularly clinical trials, in terms of time and funding, and also indirect implications for NHS patients are discussed. Inconsistencies are discussed and suggestions that could improve and streamline the overall process are made. The current approvals process could now be hindering non-commercial clinical trials, leading to a loss of important evidence-based medical information.
Exercise metaboreflex activation and endothelial function impairment in atrial fibrillation
Authors: Guazzi Marco , Berti Marco , Belletti Sebastiano , Reina Giuseppe , Guazzi Maurizio D.
Published: July 2006

Exercising muscle hypoperfusion stimulates afferents (metaboreceptors) involved in the regulation of ventilation. Atrial fibrillation (AF), particularly when combined with diseases causing endothelial (ED) impairment, such as hypertension (HP) and diabetes mellitus (DM), depresses the ED activity and enhances exercise hyperventilation. The relationship between these two functions and the underlying mechanisms have not been explored previously. In lone AF or AF associated with HP or DM (12 subjects in each cohort), we investigated the brachial artery flow-mediated dilatation (ED function) and ventilation during the recovery phase of handgrip (metaboreflex) exercise for subjects receiving placebo or oral vitamin C (double-blind crossover), both before and after cardioversion (CV) to sinus rhythm. Baseline ED impairment was increasingly more severe and the ergoreflex activity more pronounced in AF + HP and AF + DM compared with lone AF. Vitamin C and CV significantly improved both flow-mediated dilatation and metaboreflex activity in lone AF and AF + HP, and vitamin C did not produce any additive effect when administered after CV. In AF + DM, neither vitamin C nor CV was effective. This study provides the following information: AF generates oxidative injury, which is less when the arrhythmia is lone AF and greater when the arrhythmia is associated with HP. In DM, the oxidative injury generated by AF is refractory to a rather weak antioxidant, like vitamin C, or the baseline damage is such as to prevent any additive influence of AF. In AF, a cause-effect link exists between ED dysfunction and metaboreflex activity. Ventilatory advantages of CV seem to be inversely related with the extension of the underlying ED oxidative impairment.
Left ventricular myofilament dysfunction in rat experimental hypertrophy and congestive heart failure
Authors: Belin Rashad J. , Sumandea Marius P. , Kobayashi Tomoyoshi , Walker Lori A. , Rundell Veronica L. , Urboniene Dalia , Yuzhakova Milana , Ruch Stuart H. , Geenen David L. , Solaro R. John , de Tombe Pieter P.
Published: July 2006

It is currently unclear whether left ventricular (LV) myofilament function is depressed in experimental LV hypertrophy (LVH) or congestive heart failure (CHF). To address this issue, we studied pressure overload-induced LV hypertrophy (POLVH) and myocardial infarction-elicited congestive heart failure (MICHF) in rats. LV myocytes were isolated from control, POLVH, and MICHF hearts by mechanical homogenization, skinned with Triton, and attached to micropipettes that projected from a sensitive force transducer and high-speed motor. A subset of cells was treated with either unphosphorylated, recombinant cardiac troponin (cTn) or cTn purified from either control or failing ventricles. LV myofilament function was characterized by the force-[Ca2+] relation yielding Ca2+-saturated maximal force (Fmax), myofilament Ca2+ sensitivity (EC50), and cooperativity (Hill coefficient, nH) parameters. POLVH was associated with a 35% reduction in Fmax and 36% increase in EC50. Similarly, MICHF resulted in a 42% reduction in Fmax and a 30% increase in EC50. Incorporation of recombinant cTn or purified control cTn into failing cells restored myofilament Ca2+ sensitivity toward levels observed in control cells. In contrast, integration of cTn purified from failing ventricles into control myocytes increased EC50 to levels observed in failing myocytes. The Fmax parameter was not markedly affected by troponin exchange. cTnI phosphorylation was increased in both POLVH and MICHF left ventricles. We conclude that depressed myofilament Ca2+ sensitivity in experimental LVH and CHF is due, in part, to a decreased functional role of cTn that likely involves augmented phosphorylation of cTnI.