bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of Smad1 by MT1‐MMP contributes to tumor growth
Authors: Freudenberg Jaclyn A. , Chen Wen‐Tien
Published: April 2007

MT1‐MMP is a key integral membrane protease, which regulates tumor growth by cleaving extracellular matrix components, activating growth factors and receptors, and consequently, triggering downstream signals. To study what genes or pathways are mediated by endogenous MT1‐MMP during tumor growth in vivo, we stably suppressed endogenous MT1‐MMP in human tumor cells using RNA interference (RNAi). Tumor growth was significantly reduced in tumors derived from MT1‐MMP‐suppressed cells relative to control cells; the effect was rescued in cells engineered to re‐express MT1‐MMP expression. Gene expression profiling of cultured and tumor‐derived cells by DNA microarray and real‐time RT‐PCR revealed that Smad1 expression was upregulated in MT1‐MMP‐expressing cells and rapidly growing tumors; this was confirmed in 4 additional tumor cell lines. Furthermore, tumor growth of MT1‐MMP‐expressing cells was reduced when Smad1 was suppressed by RNAi. We also found that the active form, but not the latent form, of TGF‐β was capable in promoting Smad1 expression and 3D cell proliferation in MT1‐MMP‐suppressed cells. In addition, a dominant‐negative form of the TGF‐β Type II receptor reduced Smad1 expression in MT1‐MMP‐expressing cells. Thus, we propose that MT1‐MMP functions, in part, to promote tumor growth by inducing the expression of Smad1 via TGF‐β signaling. © 2007 Wiley‐Liss, Inc.
Protective effects of antioxidants on micronuclei induced by irradiated 9‐fluorenone/N,N‐dimethyl‐p‐toluidine in CHO cells
Authors: Li Yi‐Ching , Huang Fu‐Mei , Lee Shiuan‐Shinn , Lin Ruey‐Hseng , Chou Ming‐Yung , Chang Yu‐Chao
Published: April 2007

9‐Fluorenone (9F), the aromatic photosensitizer, is widely used as an initiator in visible‐light (VL) cured resin systems. There is growing concern that 9F may produce genetic damage by inducing mutation. In this study, 9F in the presence or absence of reducing agent N,N‐dimethyl‐p‐toluidine (DMT) with or without VL irradiation was analyzed for the induction of chromosomal aberrations indicated by micronuclei (MN) induced in CHO cells. Our data demonstrated that a dose‐related increase in the frequency of MN and prolonged cell cycles in 9F with or without DMT in the presence or absence of VL irradiation (p < 0.05). The rank orders with respect to genotoxicity and cytotoxicity were found to be as follows: 9F/DMT +VL > 9F/DMT = 9F + VL > 9F. To determine whether oxidative stress could modulate MN induced by 9F/DMT with or without VL irradiation in CHO cells, cells were pretreated with N‐acetyl‐L‐cysteine (NAC), ascorbic acid, and α‐tocopherol. The pretreatment with antioxidants could diminish not only the prolonged cell cycle but also the decreased frequency of MN which is induced by 9F with or without DMT in the presence or absence of VL irradiation in CHO cells (p < 0.05). Our findings provide the evidences for the induction of MN by 9F in the presence or absence of DMT with or without VL irradiation in CHO cells, indicating clastogenic activity of 9F/DMT in vitro. These antioxidants act as the antagonists against the genotoxicity and cytotoxicity of 9F/DMT. Thus, leaching photoinitiator and reducing agent might be contributing the sources of oxidative stress. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2008
Nmp4/CIZ contributes to fluid shear stress induced MMP‐13 gene induction in osteoblasts
Authors: Charoonpatrapong‐Panyayong Kanokwan , Shah Rita , Yang Jieping , Alvarez Marta , Pavalko Fredrick M. , Gerard‐O'Riley Rita , Robling Alexander G. , Templeton Evan , Bidwell Joseph P.
Published: April 2007

The expression of matrix metalloproteinase‐13 (MMP‐13), involved in bone turnover, is elevated in stretched MC3T3‐E1 osteoblast‐like cells. Strain‐mediated forces impact bone remodeling due in large part to the movement of fluid through the canalicular‐lacunar network. The resulting fluid shear stress (FSS) over the surface membranes of bone cells initiates bone remodeling. Although the nuclear events mediating putative FSS‐induced changes in osteoblast MMP‐13 transcription are unknown, previous studies with bone cells suggest an overlap between osteoblast FSS‐ and PTH‐induced signal response pathways. MMP‐13 PTH response is regulated by a 110 bp 5′ regulatory region, conserved across the mouse, rat, and human genes, that supports the binding of numerous transcription factors including Runx2, c‐fos/c‐jun, Ets‐1, and nuclear matrix protein 4/cas interacting zinc finger protein (Nmp4/CIZ) a nucleocytoplasmic shuttling trans‐acting protein that attenuates PTH‐driven transcription. Nmp4/CIZ also binds p130cas, an adaptor protein implicated in mechanotransduction. Here we sought to determine whether Nmp4/CIZ contributes to FSS‐induced changes in MMP‐13 transcription. FSS (12 dynes/cm2, 3–5 h) increased MMP‐13 promoter‐reporter activity approximately two‐fold in MC3T3‐E1 osteoblast‐like cells attended by a comparable increase in mRNA expression. This was accompanied by a decrease in Nmp4/CIZ binding to its cis‐element within the PTH response region, the mutation of which abrogated the MMP‐13 response to FSS. Interestingly, FSS enhanced Nmp4/CIZ promoter activity and induced p130cas nuclear translocation. We conclude that the PTH regulatory region of MMP‐13 also contributes to FSS response and that Nmp4/CIZ plays similar but distinct roles in mediating hormone‐ and FSS‐driven induction of MMP‐13 in bone cells. J. Cell. Biochem. 102: 1202–1213, 2007. © 2007 Wiley‐Liss, Inc.
Electrophysiological characterization of neural stem/progenitor cells during in vitro differentiation: Study with an immortalized neuroectodermal cell line
Authors: Jelitai M. , Anderová M. , Chvátal A. , Madarász E.
Published: April 2007

Despite the accumulating data on the molecular and cell biological characteristics of neural stem/progenitor cells, their electrophysiological properties are not well understood. In the present work, changes in the membrane properties and current profiles were investigated in the course of in vitro‐induced neuron formation in NE‐4C cells. Induction by retinoic acid resulted in neuronal differentiation of about 50% of cells. Voltage‐dependent Na+ currents appeared early in neuronal commitment, often preceding any morphological changes. A‐type K+ currents were detected only at the stage of network formation by neuronal processes. Flat, epithelial‐ like, nestin‐expressing progenitors persisted beside differentiated neurons and astrocytes. Stem/progenitor cells were gap junction coupled and displayed large, symmetrical, voltage‐independent currents. By the blocking of gap junction communication, voltage‐independent conductance was significantly reduced, and delayed‐rectifying K+ currents became detectable. Our data indicate that voltage‐independent symmetrical currents and gap junction coupling are characteristic physiological features of neural stem and progenitor cells regardless of the developmental state of their cellular environment. © 2007 Wiley‐Liss, Inc.
On the distribution of VOTAW's likelihood ratio criterion L for testing the bipolarity of a covariance matrix
Authors: Consul P. C.
Published: April 2007

In this paper the exact distribution function of Votaw's likelihood ratio criterion L has been obtained in the form of an infinite series by applying Mellin's transformation on the moments and then by using the asymptotic expansion for log Γ(x + h). The author has actually calculated the values of the constants for some particular cases and has shown that the first four or five terms give a high degree of accuracy. An expression for the Integral probability of the distribution has also been obtained.
On Certain Recurrence Relations
Authors: Srivastava Aruna , Gupta K. C.
Published: April 2007

In this paper first we establish six recurrence relations for the H‐function with the help of certain formulae concerning generalized BESSEL function. Later on, we obtain recurrence relations for MEIJER'S G‐function, GAUSS'S hypergeometric function and BESSEL function. On account of the general character of the H‐function, recurrence relations for other special functions can also be obtained as special cases of our results. Two well‐known results obtained earlier by Prof. MEIJER follow as special cases of our findings.
Über die Kreuzungszahl vollständiger, n‐geteilter Graphen
Authors: Harborth Heiko
Published: April 2007

Let K(x1, x2, ⃛, xn) be a graph without loops or multiple edges, the complement of which consists of n disjoint complete graphs of x1, x2, ⃛, xn vertices. In this paper a class of mappings of K(x1, ⃛, xn) onto the Euclidean plane is described. The minimum number of intersection points of edges for these mappings is determined. This number also involves an upper bound for the so‐called crossing number cr(x1, ⃛, xn), being the minimum number of intersection points of edges for all mappings of K(x1, ⃛, xn) onto the Euclidean plane (see (28)). Equality in (28) is conjectured.
On Certain Recurrence Relations II
Authors: Srivastava Aruna , Gupta K. C.
Published: April 2007

The aim of this paper is to obtain five interesting and new recurrence relations for KAMPÉ‐DE‐FÉRIET function. On account of the general nature of this function, recurrence relations for generalized hypergeometric function follow as special cases of the main results. Corresponding recurrence relations for 2F2 have also been recorded. These recurrence relations are quite interesting and have not been recorded so far. Later on we obtain interesting and new recurrence relations involving 1F2 from the earlier mentioned relations for 2F2 with the help of confluence principle. Finally by specializing the parameters we obtain various interesting recurrence relations for BESSEL function and hypergeometric function 1F2. Some of the recurrence relations recorded in this paper may find application in Physics and Applied Mathematics. The special cases of our results yield known recurrence formulae for various special functions.
Extensions of an Euler's Integral Through Statistical Techniques
Authors: Mathai A. M. , Saxena R. K.
Published: April 2007

Extensions of the Euler's integral ([4], p. 59 (10)) are given in this article. A statistical technique is used to derive the results. The exact density of a product of n stochastically independent Beta variates is obtained through two different methods, namely, through algebraic trans formations and through a moment sequence. From the unique existence of the density function, a number of results are obtained by equating the density obtained by the two methods. The technique developed in this article can be used in other situations as well.
Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC)
Authors: Zietarska Magdalena , Maugard Christine M. , Filali‐Mouhim Abdelali , Alam‐Fahmy Mona , Tonin Patricia N. , Provencher Diane M. , Mes‐Masson Anne‐Marie
Published: April 2007

Epithelial ovarian cancer (EOC) cell lines are useful tools for the molecular and biological characterization of ovarian cancer. The use of an in vitro multidimensional (3‐D) culture model recapitulates some of the growth conditions encountered by tumor cells in vivo. Here we describe a molecular comparison of spheroid based 3D EOC models versus monolayer cultures and xenografts using cell lines from malignant ovarian tumors (TOV‐21G and TOV‐112D) and ascites (OV‐90) previously established and characterized in our laboratory. Gene expression analyses of the three models were performed using the Affymetrix HG‐U133A high density DNA array. Cluster analysis identified a set of genes that stratified expression profiles from the EOC cell lines grown as spheroids and xenografts from that of monolayer cultures. The gene expression analysis results were validated by Q‐PCR analyses on an independent set of RNAs. Differential expression observed for theS100A6gene between the monolayer, spheroid cultures and xenografts was confirmed at the protein level by immunohistochemistry. The analysis was extended to various ovarian tumor tissues using an EOC tissue array. This result represents an example of a gene that, if studied in vitro, is more representative of the in vivo disease in a 3D model rather than the monolayer culture. Identification of genes in spheroid models that mimic the in vivo tumor gene expression patterns may allow a better understanding of the community effect observed in human disease that is determined by direct or indirect interactions of cells with their environment or other surrounding cells. © 2007 Wiley‐Liss, Inc.
Morphology and ultrastructure of differentiating three‐dimensional mammalian skeletal muscle in a collagen gel
Authors: Rhim Caroline , Lowell Dorothy A. , Reedy Mary C. , Slentz Dorothy H. , Zhang Sarah J. , Kraus William E. , Truskey George A.
Published: April 2007

Because previous studies of three‐dimensional skeletal muscle cultures have shown limited differentiation, the goal of this study was to establish conditions that would produce mature sarcomeres in a mammalian‐derived skeletal muscle construct. We evaluated the differentiation of bioartificial muscles generated from C2C12 myoblasts in a collagen gel cultured under steady, passive tension for up to 36 days. Staining for alpha‐actinin, myosin, and F‐actin indicated the presence of striated fibers as early as 6 days post‐differentiation. Electron microscopy at 16 days post‐differentiation revealed multinucleated myotubes with ordered, striated myofibers. At 33 days, the cultures contained collagen fibers and showed localization of paxillin at the fiber termini, suggesting that myotendinous junctions were forming. The present study demonstrates mature muscle synthesis in a three‐dimensional system using a pure mammalian myoblast cell line. Our results suggest that this culture model can be used to evaluate the effects of various mechanical and biochemical cues on muscle development under normal and pathological conditions. Muscle Nerve, 2007
The role of the printed answer in programmed instruction
Authors: Geis George L. , Jacobs William , Spencer Dwight , Nielsen Susan
Published: April 2007

Using a variety of programmed materials, this series of studies showed that students observed available answers in the program far less than 100% of the time. Answer observing was found to be correlated with student error on the related frame. The view that the printed answer in a program is always a reinforcer for the preceding response(s) is severely questioned.
CASINO V2.42—A Fast and Easy‐to‐use Modeling Tool for Scanning Electron Microscopy and Microanalysis Users
Authors: Drouin Dominique , Couture Alexandre Réal , Joly Dany , Tastet Xavier , Aimez Vincent , Gauvin Raynald
Published: April 2007

Monte Carlo simulations have been widely used by microscopists for the last few decades. In the beginning it was a tedious and slow process, requiring a high level of computer skills from users and long computational times. Recent progress in the microelectronics industry now provides researchers with affordable desktop computers with clock rates greater than 3 GHz. With this type of computing power routinely available, Monte Carlo simulation is no longer an exclusive or long (overnight) process. The aim of this paper is to present a new user‐friendly simulation program based on the earlier CASINO Monte Carlo program. The intent of this software is to assist scanning electron microscope users in interpretation of imaging and microanalysis and also with more advanced procedures including electron‐beam lithography. This version uses a new architecture that provides results twice as quickly. This program is freely available to the scientific community and can be downloaded from the website: www.gel.usherb.ca/casino. SCANNING 29: 000‐000, 2007. © 2007 Wiley Periodicals, Inc.
Mantel‐haenszel statistics and direct standardization
Authors: Woolson Robert F. , Bean Judy A.
Published: April 2007

This paper demonstrates that the Mantel‐Haenszel chi‐square statistic may be employed to test the equality of two directly standardized rates. For certain epidemiological applications, this eliminates the need for special computer programs to contrast two directly standardized rates. Furthermore, since the weights are determined entirely by the data there is the advantage of avoiding the selection of an external standard population. Data analysts who compare two groups of rates with the Mantel‐Haenszel chi‐square statistic may view this statistic as a comparative measure of two directly adjusted rates.
The design of a sequential clinical trial for the comparison of two lung cancer treatments
Authors: Jones D. R. , Newman C. E. , Whitehead J.
Published: April 2007

The steps in designing a controlled trial to evaluate a new treatment for inoperable carcinoma of the bronchus are described. The principal outcome measure is survival time from treatment allocation, and the duration of the trial is determined by application of the sequential logrank test. The detailed determination of the stopping rule and the arrangements for analyses are described.
Age, period and cohort models applied to cancer mortality rates
Authors: Osmond C. , Gardner M. J.
Published: April 2007

We develop the application of age, period and cohort models to the representation of tables of age‐ and period‐specific rates. A derivation is given by way of a familiar graphical technique. The identifiability problem is discussed, identification techniques are reviewed and a new approach is recommended that is based upon the success of the three two‐variable submodels. Other constraints are introduced that enhance interpretation. Examples are given for two sites of cancer. This approach is contrasted with other methods designed to demonstrate trends. Finally, standard errors of the parameters and tests of goodness of fit are discussed.
The use of background data in the analysis of covariance
Authors: Shirley Eryl A. C.
Published: April 2007

The advantages and disadvantages of using extraneous information about the relationship between variate and covariate in analysis of covariance are examined. The problem is considered both theoretically and by a simulation study. It is found that the usefulness of extraneous information in increasing the precision of analysis of covariance can be assessed using simple formulae.
The role of randomization in clinical trials
Authors: Armitage Peter
Published: April 2007

Random assignment of treatments is an essential feature of experimental design in general and clinical trials in particular. It provides broad comparability of treatment groups and validates the use of statistical methods for the analysis of results. Various devices are available for improving the balance of prognostic factors across treatment groups. Several recentt initiatives to diminish the role of randomization are seen as being potentially misleading. Randomization is entirely compatible with medical ethics in circumstances when the treatment of choice is not clearly identified.
On the standard error of the probability of a particular diagnosis
Authors: Machin D. , Dennis N. R. , Tippett P. A. , Andrews V.
Published: April 2007

Approximate standard errors of the probability of a particular diagnosis are given for the predictive and estimative methods described by Aitchison and Dunsmore.1 An example used in the detection of carriers of Duchenne muscular dystrophy (DMD) is given for illustration.
Discriminant analysis based on multivariate response curves: A descriptive approach to dynamic allocation
Authors: Albert Adelin
Published: April 2007

We examine the problem of discriminating between two groups in the context of multivariate response curves observed over a specified time interval. We propose a descriptive solution for the case where one can determine the response curves by linear interpolation between successive observations. Unlike most previously reported methods that use only the current multivariate observation, our approach accounts for the history of the process. Moreover the method has the potential advantage of being applicable dynamically, as one observes the multivariate response curve. Finally, the method demonstrates simplicity and flexibility, two important features for successful, routine, clinical application.
Determining reference (‘normal’) limits in medicine: An application
Authors: Bezemer P. D. , Netelenbos J. C. , Mulder C. , Theune J. A. , Stamhuis I. H. , Straus J. P.
Published: April 2007

We provide an account of a study to assess reference limits for eight routine laboratory determinations at the Academic Hospital of the Free University, Amsterdam and emphasize methodological issues rather than results. We argue that reference limits have use mainly in the first phase of the diagnostic process. Reference and target populations should be grossly comparable, and therefore patients (after slight selection) could well serve as references. However, we found major differences between in and out‐patients, so we suggest that this factor, together with age and sex, be taken into account. To arrive at reliable limits, the size of the reference sample should be at least 100. Laboratory reports should provide percentiles, which enable a more flexible decision than do fixed limits.
The analysis using genstat of anaemia, sugar intake and Quetelet's index as prognostic indicators in women
Authors: Campbell M. J.
Published: April 2007

I describe methods of analysing possible aetiological factors in a follow‐up survey, all of which are possible to carry out using the statistical package GENSTAT. A high haemoglobin level carried a significantly increased risk of ischaemic heart disease, and a low one an increased risk of cancer. Smoking was also an important factor. The increased risk was reasonably constant over time. Sugar intake and Quetelet's index did not significantly affect the relative risk.
Tests for interaction in epidemiologic studies: A review and a study of power
Authors: Greenland Sander
Published: April 2007

Tests for statistical interaction have come into increasing use in epidemiologic analysis, with most based on either an additive or multiplicative model for joint effects. Further procedures have been proposed for testing the goodness‐of‐fit and comparing the fit of the latter models. This paper reviews the relationships between the various tests and model comparison methods, and, for the special case of two dichotomous risk factors, presents asymptotic power functions for tests of additivity and multiplicativity. For a range of sample sizes and factor effects, the powers of the tests are computed using both the asymptotic power function and simulation studies. The powers of the tests are very low in several commonly encountered situations. In addition, convergence to the asymptotic distribution appears slow for some of the statistics. The results also indicate that likelihood comparison procedures can provide a useful adjunct to the classical hypothesis‐testing approach.
Comparison of models for survival data
Authors: Oakes David
Published: April 2007

Many mathematical representations are possible both for the frequency distribution of survival time and for the effect on that distribution of explanatory variables. A short review is given of the main types of model, the techniques available for model choice, the consequences of assuming a particular form and methods for assessing goodness of fit. Effects of model misspecification are discussed briefly.
Regression modelling strategies for improved prognostic prediction
Authors: Harrell Frank E. , Lee Kerry L. , Califf Robert M. , Pryor David B. , Rosati Robert A.
Published: April 2007

Regression models such as the Cox proportional hazards model have had increasing use in modelling and estimating the prognosis of patients with a variety of diseases. Many applications involve a large number of variables to be modelled using a relatively small patient sample. Problems of overfitting and of identifying important covariates are exacerbated in analysing prognosis because the accuracy of a model is more a function of the number of events than of the sample size.

We used a general index of predictive discrimination to measure the ability of a model developed on training samples of varying sizes to predict survival in an independent test sample of patients suspected of having coronary artery disease. We compared three methods of model fitting: (1) standard ‘step‐up’ variable selection, (2) incomplete principal components regression, and (3) Cox model regression after developing clinical indices from variable clusters. We found regression using principal components to offer superior predictions in the test sample, whereas regression using indices offers easily interpretable models nearly as good as the principal components models. Standard variable selection has a number of deficiencies.
Approaches to sample size estimation in the design of clinical trials—a review
Authors: Donner Allan
Published: April 2007

Over the last decade, considerable interest has focused on sample size estimation in the design of clinical trials. The resulting literature is scattered over many textbooks and journals. This paper presents these methods in a single review and comments on their application in practice.
Validity and treatment dilution in zelen's single consent design
Authors: McHugh R.
Published: April 2007

Employing randomization theory, this note examines the manner in which a clinical trial employing Zelen's randomized consent design yields an estimated treatment effect free of selection bias. We also examine the concept of ‘treatment dilution’ in this design.
Goodness‐of‐fit based confidence intervals for estimates of the size of a closed population
Authors: Regal Ronald R. , Hook Ernest B.
Published: April 2007

Methods for estimating the size of a closed population often consist of fitting some model (e.g. a log‐linear model) to data with a missing cell corresponding to the members of the population missed by all reporting sources. Although the use of the asymptotic standard error is the usual method for forming confidence intervals for the population total, the sample sizes are not always large enough to produce valid confidence intervals. We propose a method for forming confidence intervals based upon changes in a goodness‐of‐fit statistic associated with changes in trial values of the population total.
A measure to aid in the interpretation of published clinical trials
Authors: Begg Colin B.
Published: April 2007

The published literature contains numerous reports of clinical studies. A problem in their interpretation is that studies in which the observed efficacy of the treatment is high are much more likely to be reported than those in which the observed efficacy is average or poor. This phenomenon has had the consequence of generally discrediting the reliability of the literature, especially that of non‐randomized studies.

In this paper a model is developed which permits estimation of the potential magnitude by which the reported efficacy of a treatment might be inflated. This quantity is termed the publication bias. The magnitude of the bias depends on the sample size of the study and the number of similar studies conducted concurrently. Tabulated values of the bias are presented, permitting easy computation.

The new measure may have potential use for physicians in clinical decision making in that it characterizes the reliability of results from a specific published study, especially when there are no definitive randomized studies. However, correction of publication bias in this manner is not a substitute for a well controlled or a randomized study. The technique merely assists in the interpretation of available evidence from the literature. Moreover, it must be used with due caution in recognition of the assumptions and approximations involved in the calculation.
Note on interval estimation of the difference between proportions from correlated series
Authors: Hsieh Chung‐Cheng
Published: April 2007

This paper presents a procedure for estimating the confidence interval of the difference between proportions in paired observations. As an extension of McNemar's test, this large sample interval estimation procedure uses a variance estimator obtained at the limit and is not conditional on the number of discordant pairs.
On the use of the logistic model in prospective studies
Authors: Halperin Max , Abbott Robert D. , Blackwelder William C. , Jacobowitz Ronald , Gordon And K. K. Lan , Verter Joel I. , Wedel Hans
Published: April 2007

We describe the usual statistical concepts and consequent appropriate simulations of a prospective study for the simple case of a single risk variable and an assumed logistic model. We examine the simulations of Lilienfeld and Pyne,1 and show that they are seriously flawed. Contrary to those authors' claims, the estimates of parameters by the Walker‐Duncan technique are both accurate and reliable.
Prognostic factors from a randomized clinical trial in resected lung cancer
Authors: Chastang Claude , Lebeau Bernard , Charpak Yves , Decroix Guy
Published: April 2007

Prognostic information has three main uses: prediction of the course of evolution of disease, decisions about treatment and limitation of complementary tests. Using data from a randomized controlled clinical trial of immunotherapy in resected lung cancer, we identified factors of prognostic importance. In particular we demonstrated that a time‐consuming and expensive cell‐mediated immunity test is not of prognostic value. Our cooperative group decided to cancel this test in the routine examination of patients with resected lung cancer. Disease stage was confirmed as the main prognostic factor.
Correspondence analysis in a study of the clinical evolution of uncomplicated chronic relapsing alcoholic pancreatitis
Authors: Micciolo R. , Vantini I. , Cavallini G. , Piubello W. , Talamini G. , Benini L. , Scuro L. A.
Published: April 2007

This paper gives an example of the use of correspondence analysis in a study of the risk factors of surgery in uncomplicated chronic relapsing alcoholic pancreatitis (UCRAP) where censored observations are present. Ninety‐seven patients were admitted to a long‐term follow‐up project on the clinical evolution of UCRAP. During follow‐up 61 patients underwent surgery, while the observations for the remaining 36 patients were censored. Correspondence analysis was performed on three prognostic variables, selected by a preliminary univariate analysis. A supplementary variable indicating the state of each patient at a particular time (still in follow‐up, operated on, lost to follow‐up), was projected onto the best factor plane chosen by correspondence analysis. Cox's proportional hazards regression model was also used with the scores of patients on the factor axes as independent variables to evaluate their prognostic importance. Both correspondence analysis and the Cox model showed that the first two axes provide important prognostic information. Furthermore, the former suggested a pattern of censorship for patients with observations censored after 5 years of follow‐up. The results of this study confirm that correspondence analysis may be useful in follow‐up studies by providing graphic display of important information relative both about the event under study and about censored observations.
Multiplicative and additive models with external controls in a cohort study of cancer mortality
Authors: Campbell M. J.
Published: April 2007

The use of additive and multiplicative hazard models is examined for a cohort study of 2696 women followed up for 12 years. The multiplicative model implied that women with a haemoglobin level less than 12 g/dl were at higher risk from cancer, and the additive model showed that this risk was confined to women after the menopause. Despite difficulties in fitting and in interpretation, additive models can be useful in the analysis of cohort studies.
Stabilization of Substituted Triazenide Oxides: Synthesis and X‐ray Structural Features of Polymeric Potassium 3‐(4‐carboxylatophenyl)‐1‐methyltriazene N‐oxide‐hydrate, {K[O2C‐C6H4‐N(H)NN(CH3)O]·4H2O}n
Authors: Hörner Manfredo , Manzoni de Oliveira Gelson , Wohlmuth Alves dos Santos Aline Joana Rolina
Published: April 2007

3‐(4‐carboxyphenyl)‐1‐methyltriazene N‐oxide reacts with KOH in methanol/pyridine to give {K[O2C‐C6H4‐N(H)NN(CH3)O]·4H2O}n, Potassium‐3‐(4‐carboxylatophenyl)‐1‐methyltriazene N‐oxide). The terminal carboxylato group of the anion does not interact with the cation. In the crystal lattice of {K(C8H8N3O3)·4H2O}n each three of the four water molecules interact with two potassium cations, every K+ ion being the centre of six bridging K···O interactions. Potassium cations interact further with the terminal N‐oxigen atom of single [C8H8N3O3]− anions achieving two parallel {C8H8N3O3−K+}n chains, which are linked through water molecules. The resulting polymeric, one‐dimensional chain, is operated by a screw axis 21 parallel to the crystallographic direction [010], along and equidistant to the K+ centres. The coordination of the K+ centres involves a distortion of the boat conformation of elementary sulfur (S8) with the ideal C2v symmetry.
Genotype‐Phenotype Based Surgical Concept of Hereditary Medullary Thyroid Carcinoma
Authors: Machens Andreas , Dralle Henning
Published: April 2007

Background

Since DNA tests have enabled reliable identification of asymptomatic RET (rearranged during transfection) gene carriers, myriads of publications have appeared on genotype‐phenotype relationships. A comprehensive appraisal of this body of evidence using evidence‐based methodology is pending.

Methods

This study was based on systematic evaluation of the literature using evidence‐based criteria.

Results

(1) There is a distinct age‐related progression of hereditary medullary thyroid carcinoma (MTC) in carriers of RET mutations (grade C). (2) Among the high‐risk RET mutations, those in codon 634 cause higher penetrance rates of the multiple endocrine neoplasia 2A phenotype (MTC, pheochromocytoma, and parathyroid hyperplasia/adenoma) than mutations in codons 609, 611, 618, and 620, irrespective of the amino acid substituting for cysteine (grade C). (3) DNA‐based screening is superior to calcitonin‐based screening in asymptomatic RET carriers (grade C). (4) Using a worst‐case scenario, i.e., considering the earliest finding of MTC in asymptomatic RET carriers, pre‐emptive thyroidectomy should be performed before that time (grade C) to be truly prophylactic. Specifically, for carriers of highest‐risk mutations (codon 918): within the first year of life; for carriers of high‐risk mutations (codon 609, 611, 618, 620, 630, and 634): before the age of 5 years; and for carriers of least‐high risk mutations (codon 768, 790, 791, 804, and 891): before the age of 5‐10 years. Strict adherence to these grade C recommendations can result in undertreatment of the former (codon 634) and overtreatment of the latter.

Conclusions

These genotype‐phenotype correlations provide a solid foundation on which to base surgical concepts, leaving little room for randomized controlled clinical trials.
Coxsackievirus B3affects endothelial tight junctions: Possible relationship to ZO‐1 and F‐actin, as well as p38 MAPK activity
Authors: Ju Yuanrong , Wang Tao , Li Yang , Xin Wei , Wang Shuyun , Li Jianfeng
Published: April 2007

Tight junction (TJ) plays a pivotal role in preventing the invasion of pathogens from the blood to extracellular environment. However, the mechanisms by which Group B coxsackievirus 3 (CVB3) can get through TJ from the apical surface still remain obscure. In the present study, the human umbilical vein endothelial cell (HUVEC) was utilized to investigate the alterations in F‐actin and ZO‐1 status, permeability as well as p38 mitogen‐activated protein kinase (MAPK) activity in response to CVB3by means of fluorescence labeling, flow cytometry, and macromolecule permeability assay. We found that CVB3was able to induce reorganization of F‐actin and redistribution of ZO‐1, increase the level of F‐actin, and elevate the permeability of FITC‐albumin. Moreover, CVB3‐mediated the above effects involve in P38 MAPK activation. Our preliminary study indicates that CVB3‐induced alteration in permeability may be attributed to disruption of F‐actin and ZO‐1 organizations and that SB203580, a specific P38 MAPK inhibitor, can reverse these effects. The precise mechanisms underlying the CVB3‐mediated effects on HUVECs need to be studied further.
Should older adults be screened for dementia? It is important to screen for evidence of dementia!
Authors: Ashford J. Wesson , Borson Soo , O'Hara Ruth , Dash Paul , Frank Lori , Robert Philippe , Shankle William R. , Tierney Mary C. , Brodaty Henry , Schmitt Frederick A. , Kraemer Helena C. , Buschke Herman , Fillit Howard
Published: April 2007

Multiple arguments for considering routine dementia screening have been presented. Furthermore, dementia diagnoses are widely unrecognized. As a result, persons with dementia are missing important clinical care and treatment interventions. By distinction, the problems of defining, diagnosing, and treating mild cognitive impairment (MCI) are not yet resolved, and MCI is not ready for a screening recommendation. Dementia screening approaches, including cognitive testing and functional assessment, must be evaluated on their scientific merits, including sensitivity and specificity for recognizing affected individuals in at‐risk populations. Screening tests must be “cost‐worthy”, with the benefits of true‐positive test results justifying the costs of testing and resolving false‐positive cases, with due consideration for proper diagnostic evaluation and potential harms. With the tremendous number of new cases projected in the near future and the expected emergence of beneficial therapies, considerably more research is needed to develop more efficient screening systems.

Editor's Note: This paper was written in response to a comment submitted to this Journal on the consensus statement by a group of scientists concerned about screening for dementia, which was published in this Journal in April 2006 [1]. The submitted manuscript was withdrawn after this response was submitted. However, this response is being published because it addresses concerns about screening recommendations and provides clarification and additional information on key points concerning dementia screening.
Disk Structures from Triaxial Tumbling Halos
Authors: Chakrabarty Dalia , Dubinski John
Published: April 2007

In this work, we investigate the dynamical influence that external, triaxial and tumbling halos may exercise on disks that may lie embedded in them. Such halo configurations are noted in cosmological simulations, to typically rotate about their short axes, with tumbling periods of the order of a Hubble time. Thus, such halos can exert a slowly changing external torque on disks, affecting disk evolution in the process. Another source of complex dynamical effects is the probable misalignment between a disk and a triaxial dark halo. In this work, we conduct a series of experiments in which we explore the effect of a slowly changing quadrupolar tidal potential on N-body models of our Galaxy and M31; our particular aim is to check if this can induce disk structures such as bars, spirals and warps!
The Dust Content and Temperature Distribution of Galaxies in The Local Universe
Authors: Falony S. , Baes M. , Davies J. I. , Vlahakis C.
Published: April 2007

We measured the SCUBA fluxes of a sample of Seyfert 1, Seyfert 2, starburst and normal disc galaxies, taken from the Extended 12 Micron Galaxy Sample. From these data, we determine the entire dust content and temperature distribution of galaxies of different classes through a Planckian inversion technique.
Finding Double-Barred Galaxies with HST
Authors: Lisker T. , Debattista V. P. , Ferreras I. , Erwin P.
Published: April 2007

We show that the detection of double-barred (S2B) galaxies beyond the nearby universe is possible out to redshifts 0.1 ≲ z ≲ 0.5 with the resolution of the HST Advanced Camera for Surveys. We present the most distant S2B currently known, at z = 0.148.
The Spitzer Interacting Galaxies Study
Authors: Zezas A. ,   the SIGS team
Published: April 2007

Galaxy interactions play an important role in the evolution of galaxies and triggering galaxy-wide star-formation or accretion onto nuclear black-holes. However, the strength and details of the relationship between galaxy interactions and triggered activity are still unclear. In order to address these questions we embarked on a Spitzer multi-wavelength study of a sample of nearby interacting galaxy systems. Our goal is to investigate: how interactions trigger star-formation by studying the spatial distribution and level of star-formation, and comparing them with theoretical models for different interaction parameters; how the interactions drive gas in the nuclear regions, and how this gas promotes and/or hides nuclear activity, by studying the distribution of dust and performing deep spectroscopic observations of the galactic nuclei; and how star-formation and AGN activity depend on the interaction stage.
Distant Galaxy Transformation Probed by VLT and HST
Authors: Ziegler B. L. , Kutdemir E. , Böhm A. , Jäger K. , Verdugo M. , Peletier R. , Kronberger T. , Kapferer W. , Schindler S.
Published: April 2007

We investigate the morphologies and velocity fields of spiral galaxies in distant clusters (z ~ 0.5) focussing on signatures from interactions. Structural parameters and peculiarities are determined with HST/ACS images. To derive the internal kinematics and rotation curves we have performed 3D–spectroscopy allowing the construction of the full velocity field for each galaxy. Combining both approaches, transformation mechanisms are revealed that affect not only the stellar populations but also the mass distribution. The observations are supported by N-body/SPH simulations of different interaction processes.
Detection of Escaping Lyman Continuum Radiation in Two Local Starbursts Using FUSE
Authors: Leitet E. , Bergvall N. , Andersson B-G , Zackrisson E.
Published: April 2007

We present the detection of escaping Lyman Continuum (LyC) radiation from two local starburst galaxies, Tol 1247-232 and Tol 0440-381, using archival data from the Far Ultraviolet Spectroscopic Explorer (FUSE). From profile fitting of metal lines, high densities of neutral gas were derived for both galaxies, implying that the LyC radiation is escaping from holes in the interstellar medium. The first results for one of the galaxies, Tol 1247-232, give an escape fraction (fesc) of 17–35%. These new detections, together with that of the blue compact galaxy Haro 11 in Bergvall et al. (2006) where fesc between 4–10% was found, will have a feedback on cosmic reionization models.
AKARI in Orbit—Scientific Potential for Understanding Galaxy Evolution
Authors: Matsuhara H. , Murakami H. , Nakagawa T. , Wada T. , Matsuura S. , Oyabu S. , Takagi T. , Pearson C. P. , Kaneda H. , Usui F. , Shirahata M. , Shibai H. , Kawada M. , Onaka T. , Doi Y. ,   AKARI team
Published: April 2007

The AKARI (formerly known as ASTRO-F) mission is the first Japanese satellite dedicated for large area surveys in the infrared (Murakami et al. 2004). AKARI was launched successfully on February 22nd 2006 (JST) from JAXA's Uchinoura Space Centre, Japan. AKARI is now orbiting around the Earth in a Sun-synchronous polar orbit at the altitude of 700 km. The 68.5 cm aperture telescope and scientific instruments are cooled to 6K by liquid Helium and mechanical coolers. The expected liquid Helium holding time is now found to be at least one year after the successful aperture lid-opening on 2006 April 13th (JST). AKARI will perform the most advanced all-sky survey in 6 mid- to far-infrared wavebands since the preceding IRAS mission over 2 decades ago. Deep imaging and spectroscopic surveys near the ecliptic poles with pointed observations are also on-going in 13 wavelength bands at 2-160 μm (see Table 1, details are given in Matsuhara et al. 2006). AKARI is a perfect complement to Spitzer in respect of its wide sky area and wavelength coverage. Two unique aspects of the pointing deep surveys with AKARI are: many imaging bands including the wavelength gap of Spitzer (8-24 μm), and the slitless spectroscopic capability (Ohyama et al. in this proceeding). Not only the All-Sky Survey but also the deep pointing surveys near the ecliptic poles over ~15 deg2 in total will be particularly well suited to construct the luminosity functions of the infrared galaxies, to evaluate their clustering nature, and also to discover rare, exotic objects at various redshifts out to z ~ 3. AKARI is also capable of detecting and measuring the spectrum and the fluctuations of the cosmic infrared background. The in-orbit sensitivity and spatial resolution of the surveys are found to be sufficient to achive the scientific goals listed above.
Disentangling the AGN and Star-forming Contribution to the Sub-mJy Radio Counts
Authors: Seymour Nick , Moss D. , Dwelly T. , McHardy I. , Page M. , Loaring N.
Published: April 2007

The true nature of the faint radio population remains elusive despite the many observations of the “sub-mJy” bump over the last two decades. This lack of information is largely due to the faint magnitudes of the optical counterparts to the radio sources. There are strong theoretical reasons (and a few observational ones) to believe that this rise in the counts is due to the emergence of a rapidly evolving star-forming population. Now, for the first time, we are able to separate the AGN and star-forming populations below 1mJy using a combination of multi-wavelength data from Spitzer, GMRT, MERLIN, CFHT, Keck, UKIRT, Subaru, Chandra and XMM-Newton. The many discriminators between these emission mechanisms include MIR colours, MIR/radio flux ratios, X-ray luminosities/spectra, optical spectra, radio morphologies and radio spectra. We can now derive the source counts separately for AGN and star-forming galaxies confirming that the latter population rise sharply at faint flux densities.
The Star Formation History and Stellar Assembly of High Redshift Galaxies
Authors: Papovich Casey
Published: April 2007

I discuss current observational constraints on the star-formation and stellar-assembly histories of galaxies at high redshifts. The data on massive galaxies at z < 1 implies that their stellar populations formed at z>2, and that their morphological configuration was in place soon thereafter. Spitzer Space Telescope 24 μ observations indicate that a substantial fraction of massive galaxies at z ~ 1.5–3 have high IR luminosities, suggesting they are rapidly forming stars, accreting material onto supermassive black holes, or both. I compare how observations of these IR–active phases in the histories of massive galaxies constrain current galaxy–formation models.
Evolution of the rest-frame UV LF from z ~ 8 to z ~ 4
Authors: Bouwens Rychard J. , Illingworth Garth D.
Published: April 2007

We have assembled large samples of galaxies at redshift z ~ 4, 5 and 6 (totalling >4300 objects, >1000 objects, >500 objects, respectively) from all the deep HST ACS and NICMOS data taken to date (over 2000 orbits of data). From these we have derived rest-frame UV luminosity functions, luminosity densities, and star formation rates in a very robust and consistent way to very faint luminosities (0.01L* to 0.04L*). The faint-end slopes α of these luminosity functions are remarkably uniform and steep (α ~ −1.7), indicating very little evolution from z ~ 6 to z ~ 4. The characteristic luminosity L* brightens considerably (by ~1 mag) over this period, but the overall change in the luminosity function is such as to lead to little change in the luminosity density and star formation rate over this time. We also have detected galaxies at z ~ 7 − 8 and set strong limits at z ~ 10 directly from deep HST NICMOS observations. Spitzer observations of these z ~ 7 galaxies have been used to estimate masses and ages, suggesting substantial formation at z ~ 10 or earlier. These results show that this hierachical build-up continues into the reionization epoch.