bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitroInhibition of CYP3A4 Metabolism and P‐Glycoprotein‐Mediated Transport by Trade Herbal Products
Authors: Hellum Bent H. , Nilsen Odd Georg
Published: March 2008

Abstract: Extracts of six commonly used commercially available herbal products, St. John's wort, common valerian, common sage,Ginkgo biloba,Echinacea purpureaand horse chestnut were investigated for theirin vitroinhibitory potential of CYP3A4 mediated metabolism and P‐glycoprotein efflux transport activity. C‐DNA baculovirus expressed CYP3A4 and Caco‐2 cells were used. Ketoconazole and verapamil were applied as positive control inhibitors, respectively. A validated high‐performance liquid chromatography methodology was used to quantify the formation of 6‐OH‐testosterone and scintillation counting was used to quantify the transport of3H‐digoxin. All the investigated herbs inhibited CYP3A4 activity. St. John's wort was the strongest inhibiting herb with an IC50value of 15.4 µg/ml, followed by common sage,Ginkgo biloba, common valerian, horse chestnut andEchinacea purpurea. All herbs also inhibited P‐glycoprotein activity.Ginkgo bilobawas the strongest inhibiting herb, inhibiting the net digoxin flux with an IC50value of 23.6 µg/ml, followed by St. John's wort, horse chestnut, common sage, common valerian andEchinacea purpurea. No correlation was found between the herbs inhibitory potentials towards CYP3A4 and P‐glycoprotein activities.Ginkgo biloba, horse chestnut and common sage, besides St. John's wort, are suggested candidates forin vivointestinal herb‐drug pharmacokinetic interactions.
Genetic approaches to sustainable pest management in sugar beet (Beta vulgaris)
Authors: Zhang C.‐L. , Xu D.‐C. , Jiang X.‐C. , Zhou Y. , Cui J. , Zhang C.‐X. , Chen D.‐F. , Fowler M.R. , Elliott M.C. , Scott N.W. , Dewar A.M. , Slater A.
Published: March 2008

Sugar beet (Beta vulgaris) is an important arable crop, traditionally used for sugar extraction, but more recently, for biofuel production. A wide range of pests, including beet cyst nematode (Heterodera schachtii), root‐knot nematodes (Meloidogyne spp.), green peach aphids (Myzus persicae) and beet root maggot (Tetanops myopaeformis), infest the roots or leaves of sugar beet, which leads to yield loss directly or through transmission of beet pathogens such as viruses. Conventional pest control approaches based on chemical application have led to high economic costs. Development of pest‐resistant sugar beet varieties could play an important role towards sustainable crop production while minimising environmental impact. Intensive Beta germplasm screening has been fruitful, and genetic lines resistant to nematodes, aphids and root maggot have been identified and integrated into sugar beet breeding programmes. A small number of genes responding to pest attack have been cloned from sugar beet and wild Beta species. This trend will continue towards a detailed understanding of the molecular mechanism of insect–host plant interactions and host resistance. Molecular biotechnological techniques have shown promise in developing transgenic pest resistance varieties at an accelerated speed with high accuracy. The use of transgenic technology is discussed with regard to biodiversity and food safety.
Fitting orbits to tidal streams
Authors: Binney James
Published: March 2008

Recent years have seen the discovery of many tidal streams through the Galaxy. Relatively straightforward observations of a stream allow one to deduce three phase-space coordinates of an orbit. An algorithm is presented that reconstructs the missing phase-space coordinates from these data. The reconstruction starts from assumed values of the Galactic potential and a distance to one point on the orbit, but with noise-free data the condition that energy be conserved on the orbit enables one to reject incorrect assumptions. The performance of the algorithm is investigated when errors are added to the input data that are comparable to those in published data for the streams of Pal 5. It is found that the algorithm returns distances and proper motions that are accurate to of the order of 1 per cent, and enables one to reject quite resonable but incorrect trial potentials. In practical applications, it will be important to minimize errors in the imput data, and there is considerable scope for doing this.
On the relation between the radial alignment of dark matter subhaloes and host mass in cosmological simulations
Authors: Knebe Alexander , Draganova Nadya , Power Chris , Yepes Gustavo , Hoffman Yehuda , Gottlöber Stefan , Gibson Brad K.
Published: March 2008

We explore the dependence of the radial alignment of subhaloes on the mass of the host halo they orbit in. As the effect is seen on a broad range of scales including massive clusters as well as galactic systems it only appears natural to explore this phenomenon by means of cosmological simulations covering the same range in masses. We have 25 well resolved host dark matter haloes at our disposal ranging from 1015h−1 M⊙ down to 1012h−1 M⊙ each consisting of order of a couple of million particles within the virial radius. We observe that subhaloes tend to be more spherical than isolated objects. Both the distributions of sphericity and triaxiality of subhaloes are Gaussian-distributed with peak values of 〈s〉≈ 0.80 and 〈T〉≈ 0.56, irrespective of host mass. Interestingly, we note that the radial alignment is independent of host halo mass and the distribution of cos θ (i.e. the angle between the major-axis Ea of each subhalo and the radius vector of the subhalo in the reference frame of the host) is well fitted by a simple power law P(cos θ) ∝ cos4θ with the same fitting parameters for all host haloes.
CONSID: A Toolbox for Contaminant Source Identification
Authors: Sun Alexander Y.
Published: March 2008

Model‐based contaminant source identification plays an important role in effective site remediation. In this article, a contaminant source identification toolbox (CONSID) is introduced as a framework for solving contaminant source identification problems. It is known that the presence of various types of model uncertainties can severely undermine the performance of many existing source estimators. The current version of CONSID consists of two robust estimators for recovering source release histories under model uncertainty; one was developed in the deterministic framework and the other in the stochastic framework. To use the robust estimators provided in CONSID, the user is required to have only modest prior knowledge about the model uncertainty and be able to estimate the bound of model deviations resulting from the uncertainty. The toolbox is designed so that other source estimators can be added easily. A step‐by‐step guidance for using CONSID is described and an example is provided.
Implications of Rate‐Limited Mass Transfer for Aquifer Storage and Recovery
Authors: Culkin Sean L. , Singha Kamini , Day‐Lewis Frederick D.
Published: March 2008

Pressure to decrease reliance on surface water storage has led to increased interest in aquifer storage and recovery (ASR) systems. Recovery efficiency, which is the ratio of the volume of recovered water that meets a predefined standard to total volume of injected fluid, is a common criterion of ASR viability. Recovery efficiency can be degraded by a number of physical and geochemical processes, including rate‐limited mass transfer (RLMT), which describes the exchange of solutes between mobile and immobile pore fluids. RLMT may control transport behavior that cannot be explained by advection and dispersion. We present data from a pilot‐scale ASR study in Charleston, South Carolina, and develop a three‐dimensional finite‐difference model to evaluate the impact of RLMT processes on ASR efficiency. The modeling shows that RLMT can explain a rebound in salinity during fresh water storage in a brackish aquifer. Multicycle model results show low efficiencies over one to three ASR cycles due to RLMT degrading water quality during storage; efficiencies can evolve and improve markedly, however, over multiple cycles, even exceeding efficiencies generated by advection‐dispersion only models. For an idealized ASR model where RLMT is active, our simulations show a discrete range of diffusive length scales over which the viability of ASR schemes in brackish aquifers would be hindered.
Differentiation of the Local Structure Around Tryptophan 51 and 64 in Recombinant Human Erythropoietin by Tryptophan Phosphorescence
Authors: Kerwin Bruce A. , Aoki Kenneth H. , Gonelli Margherita , Strambini Giovanni B.
Published: March 2008

Recombinant human erythropoietin is a 4‐helix bundle, glycosylated cytokine containing three tryptophan residues at positions 51, 64 and 88 whose phosphorescence emission may represent a sensitive probe of the structure at multiple sites near or at the protein surface. This report characterizes the phosphorescence properties (spectral energy, thermal spectral relaxation and phosphorescence lifetime), from low temperature glasses to ambient temperature, of the native protein plus that of three single point mutation analogs where each Trp was replaced by Phe. The structural information inferred from the phosphorescence parameters was essentially in good agreement with the structure of the Escherichia coli‐produced nonglycosylated protein determined by nuclear magnetic resonance (Cheetham et al., Nat Struct Biol [1998] 5:861). The results showed that the fluorescence and phosphorescence spectra of the native protein were entirely due to independent contributions of Trp51 and Trp64 and that Trp88 was quenched under all conditions. The phosphorescence emissions of Trp51 and Trp64 were differentiated by their unique spectra at 77 K with Trp64 exhibiting an unusually blueshifted spectrum likely due to the attractive interaction of Arg110 and Lys116 with the ground state dipole of Trp64. In the native protein the room temperature phosphorescence lifetime of Trp64 was relatively short with a time of 1.62 ms whereas the lifetime of Trp51 was five‐fold longer. Characterization of the single point mutation analogs showed that each lifetime was composed of multiple components revealing the presence of multiple stable conformations of the protein at these surface sites.
Probability Integrals of the MultivariatetDistribution
Authors: Nadarajah Saralees , Kotz Samuel
Published: March 2008

Results on probability integrals of multivariatetdistributions are reviewed. The results discussed include: Dunnett and Sobel's probability integrals, Gupta and Sobel's probability integrals, John's probability integrals, Amos and Bulgren's probability integrals, Steffens' non‐central probabilities, Dutt's probability integrals, Amos' probability integral, Fujikoshi's probability integrals, probabilities of cone, probabilities of convex polyhedra, probabilities of linear inequalities, maximum probability content, and Monte Carlo evaluation.
Econometric Causality
Authors: Heckman James J.
Published: March 2008

This paper presents the econometric approach to causal modelling. It is motivated by policy problems. New causal parameters are defined and identified to address specific policy problems. Economists embrace a scientific approach to causality and model the preferences and choices of agents to infer subjective (agent) evaluations as well as objective outcomes. Anticipated and realized subjective and objective outcomes are distinguished. Models for simultaneous causality are developed. The paper contrasts the Neyman–Rubin model of causality with the econometric approach.
Anomalies in the Foundations of Ridge Regression
Authors: Jensen Donald R. , Ramirez Donald E.
Published: March 2008

Errors persist in ridge regression, its foundations, and its usage, as set forth inHoerl & Kennard (1970)and elsewhere. Ridge estimators need not be minimizing, nor a prospective ridge parameter be admissible. Conventional estimators are not LaGrange's solutions constrained to fixed lengths, as claimed, since such solutions are singular. Of a massive literature on estimation, prediction, cross–validation, choice of ridge parameter, and related issues, little emanates from constrained optimization to include inequality constraints. The problem traces to a misapplication of LaGrange's Principle, unrecognized singularities, and misplaced links between constraints and ridge parameters. Alternative principles, based on condition numbers, are seen to validate both conventional ridge andsurrogate ridgeregression to be defined. Numerical studies illustrate that ridge regression as practiced often exhibits pathologies it is intended to redress.
Mutual regulation of EBV LMP1 and CD99 in the pathogenesis of EBV‐associated Hodgkin lymphomas
Authors: Min Hye Sook , Lee Im‐Soon , Park Seong Hoe
Published: March 2008

Despite considerable progress over the last decade, Hodgkin lymphoma (HL) remains a malignant tumor of unknown pathogenesis. The role of Epstein‐Barr virus (EBV) and the activation of transcription factor NF‐κB have been noted in the tumorigenesis of classic HL. Recently, a distinctive interaction between CD99 and the EBV viral latent membrane protein 1 (LMP1) was observed in the process of the malignant transformation of EBV‐infected B cells. It was previously reported that CD99 expression is negatively regulated by LMP1, subsequently generating cells with Hodgkin and Reed‐Sternberg (HRS) cell phenotype. Interestingly, several pieces of evidence have been recently revealed the presence of mutual regulation between CD99 and LMP1, which may assist in determining HL pathogenesis. In this review, the roles of CD99 and LMP1 in the generation of the HRS cell, a tumor cell of HL, will be discussed. We also suggest that CD99 and LMP1 interaction in an in vivo system may provide new insight into the understanding of the molecular mechanism of HL.
Carbonic anhydrase II gene upregulation and tumorigenesis in Lewis lung carcinoma‐bearing mice
Authors: Seok Seung‐Hyeok , Baek Min‐Won , Lee Hui‐Young , Kim Dong‐Jae , Cho Kiho , Park Jae‐Hak
Published: March 2008

Background and aims: The carbonic anhydrases (CA), a family of metalloenzymes, play an important role in catalyzing the equilibration of carbon dioxide (CO2) and carbonic acid (H2CO3). CAs are involved in many physiological process connected with respiration and transport of CO2/bicarbonate (HCO3‐). CA inhibitors have been investigated in a variety of tumors. The role of CAs in tumorigenesis is controversial, especially in relation to the expression of CA isoenzymes between normal and malignant cells. This study was performed to elucidate the correlation of CA in the regulation of the transplant acceptance in the mice model. Methods: A rejection rate of 16.7% for transplantation, 1 × 106 cells by subcutaneous injection in the axillary region, of wild‐type Lewis lung carcinoma (LLC) cells was observed in syngeneic C57BL/6 mice. We hypothesize that the rejection is caused by the regulation of multiple genes. Differential display was performed to identify the response of genes to the rejection. Results: Initial characterization of differentially amplified products demonstrated that carbonic anhydrase II (CAII) mRNA was differently regulated in the spleens of mice bearing LLC and the spleens of non‐LLC bearing mice. RT‐PCR analysis of the mouse spleens suggested that expression of CAII was significantly increased in mice bearing LLC, when compared to non‐LLC bearing mice. Conclusions: The results indicated that CAII expression may be involved in the transplant acceptance and growth of LLC cells in the mouse model. To our knowledge, this is the first demonstration of the different of mRNA expression levels of CAII in LLC‐transplanted mice.
Pathology of lupus nephritis is better classified by the International Society of Nephrology‐Renal Pathology Society system
Authors: Seo Jinwon , Do In‐Gu , Park Eun Su , Kwon Ghee Young , Ko Young Hyeh
Published: March 2008

Background and aims: The goal of this study was to assess the diagnostic value of the new International Society of Nephrology‐Renal Pathology Society (ISN‐RPS) classification system for lupus nephritis (LN). Methods: We reviewed 170 biopsy specimens according to the WHO and the ISN‐RPS systems. Results: The frequencies of class I, class II, class III, class IV, class V, and class VI LN for the WHO/ISN‐RPS systems were 0.6%/1.8%, 2.4%/2.4%, 28.2%/24.7%, 52.4%/60%, 14.7%/9.4%, and 1.8%/1.8%, respectively. Class‐switch events occurred in 22 cases, with 12 cases switched from class III under the WHO system to class IV under the ISN‐RPS system. Class IV‐S LN showed a higher frequency of fibrinoid necrosis than IV‐G LN (P = 0.003), but endocapillary proliferation was more pronounced in class IV‐G than class IV‐S (P = 0.003). The frequency of coexistent class V LN was higher in class III LN than class IV LN (P = 0.008). The interobserver reproducibility of the ISN/RPS system was better (κ = 0.76) than that of the WHO system (κ = 0.33). Conclusions: Interobserver reproducibility for the ISN‐RPS system for lupus nephritis is greater than for the WHO system. The prognostic value of class IV‐S, IV‐G, and coexistent class V should be verified by future study.
Cutaneous hemangiosarcoma in a German Shepherd dog
Authors: Park Jin‐Kyu , Goo Moon‐Jung , Hong Il‐Hwa , Yang Hai‐Jie , Yuan Dong‐Wei , Lee Hye‐Rim , Han Jung‐Youn , Jeong Kyu‐Shik
Published: March 2008

A mass taken from the right mandibular region of a 9‐year‐old female German Shepherd dog was presented for histopathological examination. Grossly, the surgically resected 7 × 5 cm mass was dark reddish, poorly circumscribed and had infiltrated the mandibular bone. The cut surface of the mass was characterized by dark reddish parts and multi focal whitish components. Microscopically, the mass revealed locally extensive necrotic lesions with infiltration of inflammatory cells, multifocal hemorrhagic lesions and numerous hemosiderin laden macrophages. Numerous neovascular structures had been formed by atypical neoplastic tumor cells – themselves composed of undifferentiated round, ovoid, and spindle shaped neoplastic cells with pleomorphic, hyperchromatic, large nucleus and scant cytoplasm. The mass also showed abundant mitotic figures, invasions of the neovascular structures by neoplastic epitheloid tumor cells and adjacent tissue, characteristic of malignancy. The neoplastic tumor cells forming neovascular structures originated from vascular endothelial cells, therefore, the tumor was diagnosed as canine cutaneous hemangiosarcoma.
Liquid‐based cytology provides higher diagnostic accuracy than conventional Papanicolaou smears in uterine cervical cytology
Authors: Joo Hee Jae , Lee Jeongmin , Song Sang Yong , Hong Sung Ran , Jin So‐Young , Gong Gyungyub , Park Rae‐Woong , Lee Kwang Gil
Published: March 2008

Background and aims: The objective of this study was to evaluate diagnostic accuracy and cytomorphological quality of MonoPrep2 (MP) (a manual liquid‐based cytology preparation system) in comparison with the conventional Papanicolaou smear (CP) in cervical cancer screening. Methods: Six departments of pathology in university hospitals, and one pathology laboratory center, in Korea were included in the study. Retrospective analysis of 795 patients in whom CP, MP or both CP and MP with cervical biopsy had been performed was undertaken. A total of 33 cases were unsatisfactory for evaluation. A total of 933 cervical specimens (290 CP, 301 MP, and 171 CP & MP) were enrolled. Among of them, 461 cases of CP and 472 cases of MP were correlated with histopathological diagnoses. Results: Diagnostic accuracy by MP was greater than CP in all parameters including sensitivity (92.7% versus 90.2%), specificity (87.2% versus 66.2%), positive likelihood ratio (7.23 versus 2.67) and negative likelihood ratio (0.08 versus 0.15). There was marked decrease in the ratio of atypical squamous cells of undetermined significance to low‐grade squamous intraepithelial lesions. Conclusions: MP provides higher diagnostic accuracy when compared with CP. MP is an easy and economic preparation with high‐quality results, making the technique useful in primary screening for cervical cytology.
Spontaneous coronary artery dissection as a cause of sudden, unexpected death
Authors: Han Man‐Hoon , Nam Sang‐Chul , Kim Young‐Su , Lee Sang‐Han
Published: March 2008

Two cases of sudden unexpected death due to spontaneous coronary artery dissection are reported, retrieved from a series of forensic autopsies of 3300 cases since 1997. The first case was a 52‐year‐old man who had no previous health problem but cardiomegaly and atherosclerosis in coronary arteries. The dissection was found between the intima and the media at the proximal and mid‐portion of the left anterior descending coronary artery, 6.6cm in segment. The second case was a 39‐year‐old woman who had a history of hypertension and an intrauterine device. The dissection was also found between the intima and the media of the mid‐portion of the left anterior descending coronary artery, 8.7cm in segment. There was no myocardial infarct probably due to the hyperacute nature of this coronary obstruction. No significant predispositions were noted although hypertension and the intrauterine device may have causal association. Both reported cases present previously healthy adults who experienced sudden, unexpected death.
Antimicrobial Resistance of Salmonella enterica Isolates from Apparently Healthy and Clinically Ill Finishing Pigs in Spain
Authors: García‐Feliz C. , Collazos J. A. , Carvajal A. , Herrera S. , Echeita M. A. , Rubio P.
Published: March 2008

This study was the first conducted in Spain to evaluate the occurrence of antimicrobial resistance and multi‐resistance in Salmonella isolates recovered from finishing pigs from Spanish swine farms distributed over the whole country. For this purpose, 290 Salmonella isolates recovered from apparently healthy finishing pigs in a farm‐based cross‐sectional study and 192 Salmonella isolates recovered from faecal samples of finishing pigs suffering from diarrhoea were investigated. Resistance to a panel of 17 antimicrobials was determined using a broth microdilution technique. Resistance was a common finding and was detected in 90.3% of the Salmonella isolates from apparently healthy finishing pigs and 95.3% of the Salmonella isolates from clinically diseased finishing pigs. Resistance was particularly high among isolates of serogroup B and serovars Typhimurium and its monophasic variant S. 4,5,12:i:‐. Higher frequencies of resistance were found to tetracycline, sulphamethoxazole, streptomycin, spectinomycin, ampicillin, chloramphenicol and trimethoprim‐sulphamethoxazole. Less than 10% of the isolates were resistant to amoxicillin/clavulanic acid, neomycin, cephalotin, apramycin and gentamicin. Resistance to ciprofloxacin, colistin and ceftiofur was rare (under 1%). Multi‐resistance, defined as resistance to four or more drugs, was detected in more than 50% of the isolates. Although multi‐resistance was particularly frequent among isolates of S. Typhimurium, it was also high among other serovars as Bredeney and the S. Typhimurium monophasic variant. 4,5,12:i:‐.
Physiological differences between neurons in layer 2 and layer 3 of primary visual cortex (V1) of alert macaque monkeys
Authors: Gur Moshe , Snodderly D. Max
Published: March 2008

The physiological literature does not distinguish between the superficial layers 2 and 3 of the primary visual cortex even though these two layers differ in their cytoarchitecture and anatomical connections. To distinguish layer 2 from layer 3, we have analysed the response characteristics of neurons recorded during microelectrode penetrations perpendicular to the cortical surface. Extracellular responses of single neurons to sweeping bars were recorded while macaque monkeys performed a fixation task. Data were analysed from penetrations where cells could be localized to specific depths in the cortex. Although the most superficial cells (depth, 145–371 μm; presumably layer 2) responded preferentially to particular stimulus orientations, they were less selective than cells encountered immediately beneath them (depth, 386–696 μm; presumably layer 3). Layer 2 cells had smaller spikes, higher levels of ongoing activity, larger receptive field activating regions, and less finely tuned selectivity for stimulus orientation and length than layer 3 cells. Direction selectivity was found only in layer 3. These data suggest that layer 3 is involved in generating and transmitting precise, localized information about image features, while the lesser selectivity of layer 2 cells may participate in top‐down influences from higher cortical areas, as well as modulatory influences from subcortical brain regions.
Tomography-Based Determination of the Effective Thermal Conductivity of Fluid-Saturated Reticulate Porous Ceramics
Authors: Petrasch Jörg , Schrader Birte , Wyss Peter , Steinfeld Aldo
Published: March 2008

The effective thermal conductivity of reticulate porous ceramics (RPCs) is determined based on the 3D digital representation of their pore-level geometry obtained by high-resolution multiscale computer tomography. Separation of scales is identified by tomographic scans at 30μm digital resolution for the macroscopic reticulate structure and at 1μm digital resolution for the microscopic strut structure. Finite volume discretization and successive over-relaxation on increasingly refined grids are applied to solve numerically the pore-scale conduction heat transfer for several subsets of the tomographic data with a ratio of fluid-to-solid thermal conductivity ranging from 10−4 to 1. The effective thermal conductivities of the macroscopic reticulate structure and of the microscopic strut structure are then numerically calculated and compared with effective conductivity model predictions with optimized parameters. For the macroscale reticulate structure, the models by Dul’nev, Miller, Bhattachary and Boomsma and Poulikakos, yield satisfactory agreement. For the microscale strut structure, the classical porosity-based correlations such as Maxwell’s upper bound and Loeb’s models are suitable. Macroscopic and microscopic effective thermal conductivities are superimposed to yield the overall effective thermal conductivity of the composite RPC material. Results are limited to pure conduction and stagnant fluids or to situations where the solid phase dominates conduction heat transfer.
Experimental Validation of Analytical Solutions for Vertical Flat Plate of Finite Thickness Under Natural-Convection Cooling
Authors: Yadav Vipin , Kant Keshav
Published: March 2008

The analytical solution for a vertical heated plate subjected to conjugate heat transfer due to natural convection at the surface and conduction below is presented. The heated surface is split into two regions; the uniform heat flux region toward upstream and remaining fraction as the uniform wall temperature region. The fractional areas under the two regions are considered variable. Adopting thermally thin wall regime approximation, the possible solutions were investigated and found to satisfactorily deal with longitudinal conduction and temperature variation in the transverse direction. A test setup was developed and the experiments were conducted to obtain relevant data for comparison with the analytical solutions. The ranges for Rayleigh number and heat conduction parameter (α) during various test conditions were 2×108–6×108, and 0.001–1, respectively. The limiting solutions for stipulated conditions are analyzed and compared with experimental data. Reasonable agreement is observed between the experimental and analytical results.
Studies on Optimum Distribution of Fins in Heat Sinks Filled With Phase Change Materials
Authors: Saha S. K. , Srinivasan K. , Dutta P.
Published: March 2008

This paper deals with phase change material (PCM), used in conjunction with thermal conductivity enhancer (TCE), as a means of thermal management of electronic systems. Eicosane is used as PCM, while aluminium pin or plate fins are used as TCE. The test section considered in all cases is a 42×42mm2 base with a TCE height of 25mm. An electrical heater at the heat sink base is used to simulate the heat generation in electronic chips. Various volumetric fractions of TCE in the conglomerate of PCM and TCE are considered. The case with 8% TCE volume fraction was found to have the best thermal performance. With this volume fraction of TCE, the effects of fin dimension and fin shape are also investigated. It is found that a large number of small cross-sectional area fins is preferable. A numerical model is also developed to enable an interpretation of experimental results.
A Model for Neuronal Competition During Development
Authors: Deppmann Christopher D. , Mihalas Stefan , Sharma Nikhil , Lonze Bonnie E. , Niebur Ernst , Ginty David D.
Published: March 2008

We report that developmental competition between sympathetic neurons for survival is critically dependent on a sensitization process initiated by target innervation and mediated by a series of feedback loops. Target-derived nerve growth factor (NGF) promoted expression of its own receptor TrkA in mouse and rat neurons and prolonged TrkA-mediated signals. NGF also controlled expression of brain-derived neurotrophic factor and neurotrophin-4, which, through the receptor p75, can kill neighboring neurons with low retrograde NGF-TrkA signaling whereas neurons with high NGF-TrkA signaling are protected. Perturbation of any of these feedback loops disrupts the dynamics of competition. We suggest that three target-initiated events are essential for rapid and robust competition between neurons: sensitization, paracrine apoptotic signaling, and protection from such effects.
Oncogenic
CARD11
Mutations in Human Diffuse Large B Cell Lymphoma
Authors: Lenz Georg , Davis R. Eric , Ngo Vu N. , Lam Lloyd , George Thaddeus C. , Wright George W. , Dave Sandeep S. , Zhao Hong , Xu Weihong , Rosenwald Andreas , Ott German , Muller-Hermelink Hans Konrad , Gascoyne Randy D. , Connors Joseph M. , Rimsza Lisa M. , Campo Elias , Jaffe Elaine S. , Delabie Jan , Smeland Erlend B. , Fisher Richard I. , Chan Wing C. , Staudt Louis M.
Published: March 2008

Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. In the least curable (ABC) subtype of DLBCL, survival of the malignant cells is dependent on constitutive activation of the nuclear factor–κB (NF-κB) signaling pathway. In normal B cells, antigen receptor–induced NF-κB activation requires CARD11, a cytoplasmic scaffolding protein. To determine whether CARD11 contributes to tumorigenesis, we sequenced the
CARD11
gene in human DLBCL tumors. We detected missense mutations in 7 of 73 ABC DLBCL biopsies (9.6%), all within exons encoding the coiled-coil domain. Experimental introduction of CARD11 coiled-coil domain mutants into lymphoma cell lines resulted in constitutive NF-κB activation and enhanced NF-κB activity upon antigen receptor stimulation. These results demonstrate that
CARD11
is a bona fide oncogenein DLBCL, providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy.
Linked Reactivity at Mineral-Water Interfaces Through Bulk Crystal Conduction
Authors: Yanina Svetlana V. , Rosso Kevin M.
Published: March 2008

The semiconducting properties of a wide range of minerals are often ignored in the study of their interfacial geochemical behavior. We show that surface-specific charge density accumulation reactions combined with bulk charge carrier diffusivity create conditions under which interfacial electron transfer reactions at one surface couple with those at another via current flow through the crystal bulk. Specifically, we observed that a chemically induced surface potential gradient across hematite (α-Fe
2
O
3
) crystals is sufficiently high and the bulk electrical resistivity sufficiently low that dissolution of edge surfaces is linked to simultaneous growth of the crystallographically distinct (001) basal plane. The apparent importance of bulk crystal conduction is likely to be generalizable to a host of naturally abundant semiconducting minerals playing varied key roles in soils, sediments, and the atmosphere.
Clinical importance of the presence of giant cells in temporal arteritis
Authors: Armstrong A T , Tyler W B , Wood G C , Harrington T M
Published: March 2008

Background:

The clinical significance of giant cells seen on temporal artery biopsy in temporal arteritis is unknown.

Aim:

To help define the prognostic value of the presence of giant cells in temporal arteritis.

Methods:

The clinical course of all patients with biopsy proven temporal arteritis from 1994 to 2004 was reviewed. The 92 patients were divided into those with giant cells (GC) (n = 76) seen on biopsy and those with no giant cells (NGC) (n = 16). Clinical findings were compared between groups. An additional analysis combined results with a previous study at the same institution to compare occurrence of blindness.

Results:

The GC group had a higher proportion of polymyalgia rheumatica (PMR) (36.8%) compared to the NGC group (12.5%) (p = 0.059). There was no significant difference in patient age, sex, sedimentation rate, or presenting symptoms. The length of time treated with corticosteroids and relapse rate was nearly identical for both groups. When combining data with the previous study, in the GC group 21/109 (19%) developed blindness, while only 2/34 (6%) became blind in the NGC group (p = 0.11).

Conclusion:

The presence of giant cells is not a significant factor in determining treatment or clinical progression of temporal arteritis. However, results showed the GC group to have three times the occurrence of blindness and PMR compared to the NGC group. Although the differences were not significant, this analysis suggests an association with giant cells and more aggressive disease.
Aortic stent grafts
Authors: Soor G S , Chakrabarti M O , Abraham J R , Leong S W , Vukin I , Lindsay T , Butany J
Published: March 2008

Abdominal aortic aneurysms (AAAs) occur when weakened areas of the abdominal aortic wall result in a ballooning of the blood vessel. Attributed risk factors include smoking, atherosclerosis and hypertension. Traditionally, AAAs were treated with open surgery, involving a large abdominal incision and the placement of a synthetic graft. The introduction of endovascular aneurysm repair (EVAR) however, proved to have many advantages over open repair, chief among which is a lower perioperative morbidity and mortality rate. EVAR is likely to continue to evolve and the complications associated with this procedure will likely continue to decrease. In the meantime, the benefit of the continued, detailed analyses of explanted devices is twofold: (1) for future development of new devices; and (2) cognisance of complications that arise with any new device. This review is a guide to the many FDA approved stents which are commercially available, and those likely to become available following clinical trials.
The histological diagnosis of leprosy type 1 reactions: identification of key variables and an analysis of the process of histological diagnosis
Authors: Lockwood D N J , Lucas S B , Desikan K V , Ebenezer G , Suneetha S , Nicholls P
Published: March 2008

Background:

Type 1 leprosy reactions (T1R) are a major inflammatory complication of leprosy affecting 30% of patients with borderline leprosy, but there has been no diagnostic evaluation of the histological diagnosis of this entity.

Methods:

In a prospective study based in India, skin biopsies were taken from 99 patients with clinically diagnosed T1R and 52 non-reactional controls. These were assessed histologically by four histopathologists whose assessments were then compared.

Results:

Reactions were under-diagnosed, with 32–62% of clinically diagnosed reactions being given a histological diagnosis. The pathologists showed good specificities (range 72% to 93%) but much poorer sensitivities (range 42% to 78%). The most commonly reported histological features of TIR were cell maturity, oedema and giant cells. Five key variables were identified that the pathologists used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant cell numbers, dermal oedema and HLA-DR expression. A predictive model for the diagnosis of T1R was developed using stepwise logistic regression analysis, with clinical diagnosis of reaction as an outcome, and then identification of the key variables that each pathologist used in making the diagnosis of T1R. 34–53% of the variation between pathologists could be accounted for. The four pathologists used a similar diagnostic model and for all of them their estimations of epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma fraction were significant variables in the diagnosis of T1R. Each pathologist then added in variables that were specific to themselves.

Conclusions:

This study has identified T1R as being under-diagnosed in comparison with clinical assessments. Key variables for diagnosing T1R were established. This comparative masked study highlights the need for such studies in other inflammatory conditions.
A quality assurance exercise to evaluate the accuracy and reproducibility of chromogenic in situ hybridisation for HER2 analysis in breast cancer
Authors: Di Palma S , Collins N , Bilous M , Sapino A , Mottolese M , Kapranos N , Schmitt F , Isola J
Published: March 2008

Background:

Chromogenic in situ hybridisation (CISH) is an alternative to immunohistochemistry or FISH for the assessment of HER2 oncogene status in breast cancer. Although CISH is being used increasingly in routine diagnostics, there are no established inter-laboratory quality assurance programmes for this test.

Methods:

The reproducibility of HER2 CISH analysis was assessed when performed by seven different centres that use the test routinely in diagnostic service.

Results:

The results from 28 cases showed overall concordance of 98.5% (192/195 tests; κ coefficient 0.91). One of the discrepancies was due to the invasive carcinoma having been cut out in the sections received by two of the centres, and the other two were in the non-amplified/equivocal/low-amplified category.

Conclusion:

This is believed to be the first report of a quality assurance study assessing laboratories that use HER2 CISH routinely in clinical diagnostics. The results show that CISH is a robust technique providing a suitable assay for the frontline testing of HER2 status in breast cancer.
Vacuum assisted stereotactic guided mammotome biopsies in the management of screen detected microcalcifications: experience of a large breast screening centre
Authors: Kumaroswamy V , Liston J , Shaaban A M
Published: March 2008

Aim:

To evaluate the usefulness of vacuum assisted stereotactic guided mammotome biopsy in the diagnostic management of screen detected calcifications and to rationalise its use versus diagnostic excision.

Methods:

The first 100 mammotome biopsies preceded by a conventional needle core biopsy (NCB) were identified from the database of Leeds/Wakefield Breast Screening Service. The histological diagnosis on NCB and mammotome were reviewed and compared with the surgical histological diagnosis if excision had been performed.

Results:

Using mammotome, diagnoses were changed in 74 of the 100 cases. In 66 cases a definitive diagnosis (B2 or B5) was obtained. The incidence of inadequate/unsatisfactory (B1) biopsies was reduced from 36% to 9%. In 34 cases mammotome was not helpful in arriving at a definite diagnosis (B1/B3/B4). All cases diagnosed as malignant with mammotome were proven to have in situ or invasive malignancy on excision except for one case of ductal carcinoma in situ fully excised by mammotome. There was one false negative case of in-situ carcinoma with a prior benign (B2) mammotome diagnosis. Almost half the NCB uncertain (B3) cases required excision as the mammotome biopsies were also uncertain (B3). The majority were flat epithelial atypia and atypical intraductal proliferation.

Conclusions:

Mammotome biopsy is particularly useful for further assessment of an inadequate (B1) or suspicious (B4) NCB diagnosis. Diagnostic surgical excision remains the method of choice for managing atypical/uncertain lesions (B3).
High expression of Polycomb group protein EZH2 predicts poor survival in salivary gland adenoid cystic carcinoma
Authors: Vékony H , Raaphorst F M , Otte A P , van Lohuizen M , Leemans C R , van der Waal I , Bloemena E
Published: March 2008

Background:

The prognosis of adenoid cystic carcinoma (ACC), a malignant salivary gland tumour, depends on clinicopathological parameters. To decipher the biological behaviour of ACC, and to identify patients at risk of developing metastases, additional markers are needed.

Methods:

Expression of the cell cycle proteins p53, cyclin D1, p16INK4a, E2F1 and Ki-67, together with the Polycomb group (PcG) proteins BMI-1, MEL-18, EZH2 and EED was investigated immunohistochemically 21 formalin-fixed, paraffin-embedded primary ACCs in relation to tumour characteristics.

Results:

ACC revealed significantly increased expression of the cell cycle proteins compared to normal salivary tissue (n = 17). Members of the two PcG complexes displayed mutually exclusive expression in normal salivary gland tissue, with BMI-1 and MEL-18 being abundantly present. In ACC, this expression pattern was disturbed, with EZH2 and EED showing significantly increased expression levels. In univariate analysis, presence of recurrence, poor differentiation and high EZH2 levels (>25% immunopositivity) significantly correlated with unfavourable outcome. ACCs with high proliferative rate (>25% Ki-67 immunopositivity) significantly correlated with high levels of EZH2 and p16. Only the development of recurrence was an independent prognostic factor of survival in multivariate analysis.

Conclusions:

Expression of PcG complexes and of essential cell cycle proteins is highly deregulated in ACC. Also, EZH2 expression has prognostic relevance in this malignancy.
Transient receptor potential vanilloid 4 mediates protease activated receptor 2-induced sensitization of colonic afferent nerves and visceral hyperalgesia
Authors: Sipe Walter E. B. , Brierley Stuart M. , Martin Christopher M. , Phillis Benjamin D. , Cruz Francisco Bautista , Grady Eileen F. , Liedtke Wolfgang , Cohen David M. , Vanner Stephen , Blackshaw L. Ashley , Bunnett Nigel W.
Published: March 2008

Protease-activated receptor (PAR2) is expressed by nociceptive neurons and activated during inflammation by proteases from mast cells, the intestinal lumen, and the circulation. Agonists of PAR2 cause hyperexcitability of intestinal sensory neurons and hyperalgesia to distensive stimuli by unknown mechanisms. We evaluated the role of the transient receptor potential vanilloid 4 (TRPV4) in PAR2-induced mechanical hyperalgesia of the mouse colon. Colonic sensory neurons, identified by retrograde tracing, expressed immunoreactive TRPV4, PAR2, and calcitonin gene-related peptide and are thus implicated in nociception. To assess nociception, visceromotor responses (VMR) to colorectal distension (CRD) were measured by electromyography of abdominal muscles. In TRPV4+/+ mice, intraluminal PAR2 activating peptide (PAR2-AP) exacerbated VMR to graded CRD from 6–24 h, indicative of mechanical hyperalgesia. PAR2-induced hyperalgesia was not observed in TRPV4−/− mice. PAR2-AP evoked discharge of action potentials from colonic afferent neurons in TRPV4+/+ mice, but not from TRPV4−/− mice. The TRPV4 agonists 5′,6′-epoxyeicosatrienoic acid and 4α-phorbol 12,13-didecanoate stimulated discharge of action potentials in colonic afferent fibers and enhanced current responses recorded from retrogradely labeled colonic dorsal root ganglia neurons, confirming expression of functional TRPV4. PAR2-AP enhanced these responses, indicating sensitization of TRPV4. Thus TRPV4 is expressed by primary spinal afferent neurons innervating the colon. Activation of PAR2 increases currents in these neurons, evokes discharge of action potentials from colonic afferent fibers, and induces mechanical hyperalgesia. These responses require the presence of functional TRPV4. Therefore, TRPV4 is required for PAR2-induced mechanical hyperalgesia and excitation of colonic afferent neurons.
Differential mechanisms of hepatic vascular dysregulation with mild vs. moderate ischemia-reperfusion
Authors: Lee Sang Ho , Culberson Cathy , Korneszczuk Katarzyna , Clemens Mark G.
Published: March 2008

Endotoxemia produces hepatic vascular dysregulation resulting from inhibition of endothelin (ET)-stimulated NO production. Mechanisms include overexpression of caveolin-1 (Cav-1) and altered phosphorylation of endothelial nitric oxide (NO) synthase (NOS; eNOS) in sinusoidal endothelial cells. Since ischemia-reperfusion (I/R) also causes vascular dysregulation, we tested whether the mechanisms are the same. Rats were exposed to either mild (30 min) or moderate (60 min) hepatic ischemia in vivo followed by reperfusion (6 h). Livers were harvested and prepared into precision-cut liver slices for in vitro analysis of NOS activity and regulation. Both I/R injuries significantly abrogated both the ET-1 (1 μM) and the ETB receptor agonist (IRL-1620, 0.5 μM)-mediated stimulation of NOS activity. 30 min I/R resulted in overexpression of Cav-1 and loss of ET-stimulated phosphorylation of Ser1177 on eNOS, consistent with an inflammatory response. Sixty-minute I/R also resulted in loss of ET-stimulated Ser1177 phosphorylation, but Cav-1 expression was not altered. Moreover, expression of ETB receptors was significantly decreased. This suggests that the failure of ET to activate eNOS following 60-min I/R is associated with decreased protein expression consistent with ischemic injury. Thus hepatic vascular dysregulation following I/R is mediated by inflammatory mechanisms with mild I/R whereas ischemic mechanisms dominate following more severe I/R stress.
Progressive nature of chronic mitral regurgitation and the role of tissue Doppler-derived indexes
Authors: Neilan Tomas G. , Ton-Nu Thanh-Thao , Kawase Yoshiaki , Yoneyama Ryuichi , Hoshino Kozo , del Monte Federica , Hajjar Roger J. , Picard Michael H. , Levine Robert A. , Hung Judy
Published: March 2008

The aim of this study was to determine whether severe mitral regurgitation (MR) is progressive and whether tissue-Doppler (TD)-derived indexes can detect early left ventricular (LV) dysfunction in chronic severe MR. Percutaneous rupture of mitral valve chordae was performed in pigs ( n = 8). Before MR (baseline), immediately after MR (post-MR), and at 1 and 3 mo after MR, cardiac function was assessed using conventional and TD-derived indexes. The severity of MR was quantified using regurgitant fraction and effective regurgitant orifice area (EROA). In all animals, MR was severe. On follow-up, the LV dilated progressively over time, but LV ejection fraction did not decrease. With the increase in LV dimensions, the forward stroke volume remained unchanged, but the mitral annular dimensions, EROA, and regurgitant fraction increased (EROA = 41 ± 2 and 51 ± 2 mm2 post-MR and at 3 mo, respectively, P < 0.01). Peak systolic myocardial velocities, strain, and strain rate increased acutely post-MR and remained elevated at 1 mo but declined by 3 mo (anterior strain rate = 2.9 ± 0.1 and 2.4 ± 0.2 s−1 post-MR and at 3 mo, respectively, P < 0.001). Therefore, in a chronic model of MR, serial echocardiography demonstrated that MR begets MR and that those TD-derived indexes that initially increased post-MR decreased to baseline before any changes in LV ejection fraction.