bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrafamilial Variability of Early-Onset Diabetes due to anINSMutation
Authors: Fredheim Siri , Svensson Jannet , Pørksen Sven , Hansen Lars , Hansen Torben , Pedersen Oluf Borbye , Mortensen Henrik Bindesbøl , Barbetti Fabrizio , Nielsen Lotte Brøndum
Published: June 2011

Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene.Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule causing permanent neonatal diabetes. All three were diagnosed before 29 weeks of age, were born at term with near-normal birth weight, and were negative for GAD, ICA, IA-2, and IAA autoantibodies. The daily insulin requirement the first six months after diagnosis was <0.5 U kg−1day−1for both children. The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy.Conclusions. These three cases further confirm the essential features of diabetes caused byINSmutations with proteotoxic effect. We conclude that patients with similar features must be investigated for mutations ofINSgene.
Left WMC2 Rings
Authors: Wei Junchao
Published: June 2011

We introduce in this paper the concept of left WMC2 rings and concern ourselves with rings containing an injective maximal left ideal. Some known results for left idempotent reflexive rings and left HI rings can be extended to left WMC2 rings. As applications, we are able to give some new characterizations of regular left self‐injective rings with nonzero socle and extend some known results on strongly regular rings.
Evaluation of Behavioral and Pharmacological Effects of Hydroalcoholic Extract of Valeriana prionophylla Standl. from Guatemala
Authors: Holzmann Iandra , Cechinel Filho Valdir , Mora Ticiana C. , Cáceres Armando , Martínez Jose Vicente , Cruz Sully M. , de Souza Márcia Maria
Published: June 2011

There are few studies on the pharmacological properties of Valeriana prionophylla Standl. (VP), known as “Valeriana del monte”, and used in Mesoamerican folk medicine to treat sleep disorders. This study examines the pharmacological effects of the hydroalcoholic extract of the dry rhizome using the open field, rota rod, elevated plus‐maze (EPM), forced swimming (FST), strychnine‐ and pentobarbital‐induced sleeping time, PTZ‐induced seizures, and the inhibitory avoidance tests. VP did not show any protective effect against PTZ‐induced convulsions. In the EPM, exhibited an anxiolytic‐like effect through the effective enhancement of the entries (38.5%) and time spent (44.7%) in the open arms, when compared with control group. Time spent and the numbers of entrances into the enclosed arms were decreased, similar to those effects observed with diazepam. In the FST, acute treatment with VP, produced a dose‐dependent decrease in immobility time, similarly to imipramine. VP also produced a significant dose‐dependent decrease in the latency of sleeping time, while producing an increase in total duration of sleep; influenced memory consolidation of the animals only at lower doses, unlike those that produced anti‐depressant and anxiolytic effects. In summary, the results suggest that VP presents several psychopharmacological activities, including anxiolytic, antidepressant, and hypno‐sedative effects.
On the Strong Convergence of Viscosity Approximation Process for Quasinonexpansive Mappings in Hilbert Spaces
Authors: Wongchan Kanokwan , Saejung Satit
Published: June 2011

We improve the viscosity approximation process for approximation of a fixed point of a quasi‐nonexpansive mapping in a Hilbert space proposed by Maingé (2010). An example beyond the scope of the previously known result is given.
Asymptomatic Presentation of Aggressive Ossifying Fibroma:A Case Report
Authors: Kashyap Roopashri Rajesh , Nair Gopakumar R. , Gogineni Subhas Babu
Published: June 2011

Ossifying fibromas form a part of the spectrum of fibro-osseous lesions of the jaws. They are rare, benign, nonaggressive tumors that are commonly seen in head and neck region. This paper presents the case of a 40-year-old female patient presented with minimal clinical symptoms, diagnosed to be suffering from aggressive form of ossifying fibroma of maxilla involving the maxillary sinus and ethmoid sinus. This paper emphasizes the importance of computed tomography in diagnosing such unapparent aggressive tumors.
Epstein-Barr Virus Reactivation after Infliximab in Rheumatoid Arthritis: A Case Report
Authors: Colaci Michele , Sebastiani Marco , Sandri Gilda , Meacci Marisa , Ferri Clodoveo
Published: June 2011

TNF-alpha blockers represent one of the most important therapeutic strategies for rheumatoid arthritis, but their use has raised the question about their safety profile, particularly in respect to viral infections/reactivations. We describe the case of a patient who developed a symptomatic EBV reactivation 11 days after the first infusion of infliximab.
Connexin43 Expression Increases in the Epithelium and Stroma along the Colonic Neoplastic Progression Pathway: Implications for Its Oncogenic Role
Authors: Han Yusheng , Zhang Paul J. , Chen Terina , Yum Sabrina W. , Pasha Teresa , Furth Emma E.
Published: June 2011

Connexins (Cxs) are critical for normal tissue development, differentiation, and cell proliferation. Normal expression and function of Cxs are considered to play a role in tumor suppression, but abnormal localization and abnormally increased expression of Cxs have been found in a variety of carcinomas. Of the Cx family, Cx43 is a most prevalent member and has been known as a downstream target of β-catenin, a key component of Wnt signaling pathway. We evaluated the expression of Cx43 in the colonic neoplasia progression sequence with additional attention to the stromal component. Resections of 50 colonic adenocarcinomas were stained immunohistochemically for Cx43 on paraffin embedded sections. Cx43 cytoplasmic expression increased progressively in the colonic adenocarcinoma sequence in both the epithelial [normal (4±1), adenomatous (20±2), cancerous (124±10) (P<0.01)], and stromal [normal (19±1), cancerous (45±4) (P<0.01)] components. In the epithelial component, Cx43 was expressed lower in stage I adenocarcinomas (69±12) compared to stage III/IV (158±10,P<0.01). Additionally, Cx43 was relatively increased in the adenocarcinoma at the invasive tumor front in all stages. Cx43 may play a critical role in the pathogenesis of colon cancer via gap junction or other gap junction independent mechanisms such as the Wnt/β-catenin pathway.
Uveal Melanoma
Authors: Papastefanou Vasilios P. , Cohen Victoria M. L.
Published: June 2011

Uveal melanoma is the most common primary intraocular malignancy and the leading primary intraocular disease which can be fatal in adults. In this paper epidemiologic, pathogenetic, and clinical aspects of uveal melanoma are discussed. Despite the advance in local ocular treatments, there has been no change in patient survival for three decades. Development of metastases affects prognosis significantly. Current survival rates, factors predictive of metastatic potential and metastatic screening algorithms are discussed. Proposed and emerging treatments for uveal melanoma metastases are also overviewed. Current advances in genetics and cytogenetics have provided a significant insight in tumours with high metastatic potential and the molecular mechanisms that underlie their development. Biopsy of those lesions may prove to be important for prognostication and to allow further research into genetic mutations and potential new therapeutic targets in the future.
Tuning Expert Systems for Cost-Sensitive Decisions
Authors: Sinha Atish P. , Zhao Huimin
Published: June 2011

There is currently a growing body of research examining the effects of the fusion of domain knowledge and data mining. This paper examines the impact of such fusion in a novel way by applying validation techniques and training data to enhance the performance of knowledge-based expert systems. We present an algorithm for tuning an expert system to minimize the expected misclassification cost. The algorithm employs data reserved for training data mining models to determine the decision cutoff of the expert system, in terms of the certainty factor of a prediction, for optimal performance. We evaluate the proposed algorithm and find that tuning the expert system results in significantly lower costs. Our approach could be extended to enhance the performance of any intelligent or knowledge system that makes cost-sensitive business decisions.
Solutions of Smooth Nonlinear Partial Differential Equations
Authors: van der Walt Jan Harm
Published: June 2011

The method of order completion provides a general and type‐independent theory for the existence and basic regularity of the solutions of large classes of systems of nonlinear partial
differential equations (PDEs). Recently, the application of convergence spaces to this theory resulted in a significant
improvement upon the regularity of the solutions and provided new insight into the structure of solutions. In this paper, we show how this method may be adapted so as to allow for the infinite differentiability of generalized functions. Moreover, it is shown that a large class of smooth nonlinear PDEs admit generalized solutions in the space constructed here. As an indication of how the general theory can be applied to particular nonlinear equations, we construct generalized solutions of the
parametrically driven, damped nonlinear Schrödinger equation in one spatial dimension.
Mutations in TP53 and CTNNB1 in Relation to Hepatitis B and C Infections in Hepatocellular Carcinomas from Thailand
Authors: Galy Olivier , Chemin Isabelle , Le Roux Emilie , Villar Stéphanie , Le Calvez-Kelm Florence , Lereau Myriam , Gouas Doriane , Vieco Beatriz , Suarez Iris , Navas Maria-Cristina , Chevallier Michèle , Norder Helene , Srivatanakul Petcharin , Karalak Anant , Sangrajrang Suleeporn , Trépo Christian , Hainaut Pierre
Published: June 2011

Hepatocellular carcinoma (HCC) may develop according to two major pathways, one involving HBV infection and TP53 mutation and the other characterized by HCV infection and CTNNB1 mutation. We have investigated HBV/HCV infections and TP53/CTNNB1 mutations in 26 HCC patients from Thailand. HBV DNA (genotype B or C) was detected in 19 (73%) of the cases, including 5 occult infections and 3 coinfections with HCV. TP53 and CTNNB1 mutations were not mutually exclusive, and most of TP53 mutations were R249S, suggesting a significant impact of aflatoxin-induced mutagenesis in HCC development.
Delay‐Dependent H∞ Filtering for Singular Time‐Delay Systems
Authors: Li Zhenbo , Zhu Shuqian
Published: June 2011

This paper deals with the problem of delay‐dependent H∞ filtering for singular time‐delay systems. First, a new delay‐dependent condition which guarantees that the filter error system has a prescribed H∞ performance γ is given in terms of linear matrix inequalities (LMIs). Then, the sufficient condition is obtained for the existence of the H∞ filter, and the explicit expression for the desired H∞ filter is presented by using LMIs and the cone complementarity linearization iterative algorithm. A numerical example is provided to illustrate the effectiveness of the proposed method.
Efficacy of Diosmectite (Smecta)®in the Treatment of Acute Watery Diarrhoea in Adults: A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study
Authors: Khediri Faouzi , Mrad Abdennebi Ilhem , Azzouz Moussadek , Doughi Hedi , Najjar Taoufik , Mathiex-Fortunet Hélène , Garnier Philippe , Cortot Antoine
Published: June 2011

Background. Although diosmectite has demonstrated efficacy in the treatment of acute watery diarrhoea in children, its efficacy in adults still needs to be assessed. The objective of this study was therefore to assess the efficacy of diosmectite on the time to recovery in adults with acute diarrhoea.Methods. A total of 346 adults with at least three watery stools per day over a period of less than 48 hours were prospectively randomized to diosmectite (6 g tid) or placebo during four days. The primary endpoint was time to diarrhoea recovery.Results. In the intention-to-treat population, median time to recovery was 53.8 hours (range [3.7–167.3]) with diosmectite (n=166) versus 69.0 hours [2.2–165.2] with placebo, (n=163;P=.029), which corresponds to a difference of 15.2 hours. Diosmectite was well tolerated.Conclusion. Diosmectite at 6 g tid was well tolerated and reduced the time to recovery of acute watery diarrhoea episode in a clinically relevant manner.
Protection against Autoimmune Diabetes by Silkworm-Produced GFP-Tagged CTB-Insulin Fusion Protein
Authors: Meng Qiaohong , Wang Wenfeng , Shi Xiaowen , Jin Yongfeng , Zhang Yaozhou
Published: June 2011

In animals, oral administration of the cholera toxin B (CTB) subunit conjugated to the autoantigen insulin enhances the specific immune-unresponsive state. This is called oral tolerance and is capable of suppressing autoimmune type 1 diabetes (T1D). However, the process by which the CTB-insulin (CTB-INS) protein works as a therapy for T1Din vivoremains unclear. Here, we successfully expressed a green fluorescent protein- (GFP-) tagged CTB-Ins (CTB-Ins-GFP) fusion protein in silkworms in a pentameric form that retained the native ability to activate the mechanism. Oral administration of the CTB-Ins-GFP protein induced special tolerance, delayed the development of diabetic symptoms, and suppressed T1D onset in nonobese diabetic (NOD) mice. Moreover, it increased the numbers of CD4+CD25+Foxp3+T regulatory (Treg) cells in peripheral lymph tissues and affected the biological activity of spleen cells. This study demonstrated that the CTB-Ins-GFP protein produced in silkworms acted as an oral protein vaccine, inducing immunological tolerance involving CD4+CD25+Foxp3+Treg cells in treating T1D.
A Novel EPO Receptor Agonist Improves Glucose Tolerance via Glucose Uptake in Skeletal Muscle in a Mouse Model of Diabetes
Authors: Scully Michael S. , Ort Tatiana A. , James Ian E. , Bugelski Peter J. , Makropoulos Dorie A. , Deutsch Heather A. , Pieterman Elsbet J. , van den Hoek Anita M. , Havekes Louis M. , duBell William H. , Wertheimer Joshua D. , Picha Kristen M.
Published: June 2011

Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of -2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-αand darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.
Strategic Framework for Increasing Accessibility and Utilization of Voluntary Counseling and Testing Services in Uganda
Authors: Mugisha E. , van Rensburg G. H. , Potgieter E.
Published: June 2011

Despite the usefulness of VCT service as an entry point to prevention for the HIV-uninfected people and care, treatment and support for those who test HIV positive, VCT service remains poorly utilized among the fishing communities. The aim of the study was to identify factors influencing VCT service delivery and utilisation among fishing communities in Uganda and consequently, formulated a strategic framework for improving VCT service delivery and utilisation in the fishing communities. The study followed a 3-phased approach, collecting and analyzing quantitative data from Kasenyi fishing community under phase I, collecting and analyzing qualitative data from hospital managers and VCT counselors in phases II and III, respectively. Results indicate that VCT services delivery and utilisation is affected by factors at government (macro) level, the institution (meso) level, and at the individual (micro) level. Based on this, a strategic framework was designed, expected to increase VCT service availability, accessibility, and acceptability if applied. The researcher recommends the use of this useful tool in the design of VCT programs.
Massive Hematochezia: A Complication of Methamphetamine-Induced Vasculitis Treated by Transcatheter Hemostasis
Authors: Link Daniel P. , Chi Yung-Wei
Published: June 2011

A long-term, heavy methamphetamine user with life-threatening rectal hemorrhage was treated with transcatheter occlusion of the bleeding arteries. The bleeding blood vessels were vulnerable submucosal arteries, part of the collateral supply to the distal colon. Visceral arteriography demonstrates severe arterial stenotic lesions of the celiac axis, superior mesenteric artery and the inferior mesenteric artery. Collateral vessels were seen with corkscrew morphology similar to that seen with thromboangiitis obliterans.
Randomness and Topological Invariants in Pentagonal Tiling Spaces
Authors: Escudero Juan García
Published: June 2011

We analyze substitution tiling spaces with fivefold symmetry. In the substitution process, the introduction of randomness can be done by means of two methods which may be combined: composition of inflation rules for a given prototile set and tile rearrangements. The configurational entropy of the random substitution process is computed in the case of prototile subdivision followed by tile rearrangement. When aperiodic tilings are studied from the point of view of dynamical systems, rather than treating a single one, a collection of them is considered. Tiling spaces are defined for deterministic substitutions, which can be seen as the set of tilings that locally look like translates of a given tiling. Čech cohomology groups are the simplest topological invariants of such spaces. The cohomologies of two deterministic pentagonal tiling spaces are studied.
Evaluation of the Antimicrobial Activity of the Decoction ofTropidurus hispidus(Spix, 1825) andTropidurus semitaeniatus(Spix, 1825) Used by the Traditional Medicine
Authors: Santos Israel J. M. , Matias Edinardo F. F. , Santos Karla K. A. , Braga Maria F. B. M. , Andrade Jacqueline C. , Souza Teógenes M. , Santos Francisco A. V. , Sousa Ana Carla A. , Costa José G. M. , Menezes Irwin R. A. , Alves Rômulo R. N. , Almeida Waltecio O. , Coutinho Henrique D. M.
Published: June 2011

Tropidurus hispidusandTropidurus semitaeniatusare two lizard species utilized in traditional medicine in Northeast Brazil. Their medicinal use includes diseases related with bacterial infections such as tonsillitis and pharyngitis. They are used in the form of teas (decoctions) for the treatment of illnesses. In this work, we evaluated the antimicrobial activity of the decoctions ofT. hispidus(DTH) andT. semitaeniatus(DTS) against bacterial strains, namely, standard and multiresistantEscherichia coli,Staphylococus aureus, andPseudomonas aureuginosa, alone and in combination with aminoglycoside antibiotics. The decoctions were prepared using the whole body of the dried lizards, and the filtrate was frozen and lyophilized. When tested alone, the samples did not demonstrate any substantial inhibition of bacterial growth. However, in combination with antibiotics as aminoglycosides, decoctions reduced the minimal inhibitory concentration (MIC) of the assayed antibiotics against multiresistant strains ofS. aureusandP. aureuginosa. Chemical prospecting tests revealed the presence of alkaloids in DTS. This is the first study evaluating the medicinal efficacy ofT. hispidusandT. semitaeniatusand contributes to the list of new sources of medicines from natural products of animal origin.
VHL Gene Mutations and Their Effects on Hypoxia Inducible Factor HIFα: Identification of Potential Driver and Passenger Mutations
Authors: Rechsteiner Markus P. , von Teichman Adriana , Nowicka Anna , Sulser Tullio , Schraml Peter , Moch Holger
Published: June 2011

Mutations of the von Hippel-Lindau (VHL) gene are frequent in clear cell renal cell carcinomas (ccRCC). Nonsense and frameshift mutations abrogate the function of the VHL protein (pVHL), whereas missense mutations can have different effects. To identify those missense mutations with functional consequences, we sequenced VHL in 256 sporadic ccRCC and identified 187 different VHL mutations of which 65 were missense mutations. Location and destabilizing effects of VHL missense mutations were determined in silico. The majority of the thermodynamically destabilizing missense mutations were located in exon 1 in the core of pVHL, whereas protein surface mutations in exon 3 affected the interaction domains of elongin B and C. Their impact on pVHL's functionality was further investigated in vitro by stably reintroducing VHL missense mutations into a VHL null cell line and by monitoring the green fluorescent protein (GFP) signals after the transfection of a hypoxia inducible factor (HIF)α-GFP expression vector. pVHL's functionality ranged from no effect to complete HIF stabilization. Interestingly, Asn78Ser, Asp121Tyr, and Val130Phe selectively influenced HIF1α and HIF2α degradation. In summary, we obtained three different groups of missense mutations: one with severe destabilization of pVHL; a second without destabilizing effects on pVHL but relevance for the interaction with HIFα, elongin B, and elongin C; and a third with pVHL functions comparable with wild type. We therefore conclude that the specific impact of missense mutations may help to distinguish between driver and passenger mutations and may explain responses of ccRCC patients to HIF-targeted therapies. Cancer Res; 71(16); 5500–11. ©2011 AACR.
Two-Stage Design of Sequencing Studies for Testing Association with Rare Variants
Authors: Yang Fan , Thomas Duncan C.
Published: July 2011

Multiple rare variants have been suggested as accounting for some of the associations with common single nucleotide polymorphisms identified in genome-wide association studies or possibly some of the as yet undiscovered heritability. We consider the power of various approaches to designing substudies aimed at using next-generation sequencing technologies to discover novel variants and to select some subsets that are possibly causal for genotyping in the original case-control study and testing for association using various weighted sum indices. We find that the selection of variants based on the statistical significance of the case-control difference in the subsample yields good power for testing rare variant indices in the main study, and that multivariate models including both the summary index of rare variants and the associated common single nucleotide polymorphisms can distinguish which is the causal factor. By simulation, we explore the effects of varying the size of the discovery subsample, choice of index, and true causal model.
Mosaicism in Segmental Darier Disease: An In-Depth Molecular Analysis Quantifying Proportions of Mutated Alleles in Various Tissues
Authors: Harboe Theresa Larriba , Willems Patrick , Jespersgaard Cathrine , Mølgaard Poulsen Marie Louise , Sørensen Flemming Brandt , Bisgaard Marie Luise
Published: July 2011

Darier disease is an autosomal dominant genodermatosis caused by germline mutations in the ATP2A2 gene. Clinical expression is variable, including rare segmental phenotypes thought to be caused by postzygotic mosaicism. Genetic counseling of segmental Darier patients is complex, as risk of transmitting a nonsegmental phenotype to offspring is of unknown magnitude. We present the first in-depth molecular analysis of a mosaic patient with segmental disease, quantifying proportions of mutated and normal alleles in various tissues. Pyrosequence analysis of DNA from semen, affected and normal skin, peripheral leukocytes and hair revealed an uneven distribution of the mutated allele, from 14% in semen to 37% in affected skin. We suggest a model for segmental manifestation expression where a threshold number of mutated cells is needed for manifestation development. We further recommend molecular analysis of the ATP2A2 gene in semen of male patients with segmental Darier disease to improve genetic counseling.
Clinical Characteristics and Cardiovascular Outcomes of Hemodialysis Patients with Atrial Fibrillation: A Prospective Follow-Up Study
Authors: Fujii Hideki , Kim Jong-Il , Yoshiya Kunihiko , Nishi Shinichi , Fukagawa Masafumi
Published: June 2011

Background/Aims: Among the cardiovascular complications in dialysis patients, atrial fibrillation (AF) is the most common arrhythmia. The purpose of this study was to clarify the characteristics and mortality of hemodialysis patients with AF, which are not completely elucidated. Methods: The prevalence of AF in patients undergoing hemodialysis in our institutions was assessed. Patients with AF (AF group) and without AF (control group) were included in this study. Patients in the control group were matched for several important clinical risk factors. For further analysis, AF patients were divided into two groups on the basis of the type of AF (chronic AF (CAF) and paroxysmal AF (PAF) groups). These patients were evaluated for their clinical characteristics, laboratory data and echocardiographic parameters and prospectively followed up for 48 months. Results: Among 328 study patients, 30 had AF (9.1%). Left atrial diameter (LAD) and the left ventricular mass index were significantly greater in the AF group than in the control group. Furthermore, cardiovascular and all-cause mortality and cumulative incidence of cardiovascular events were significantly higher in the AF group than in the control group, and tended to be higher in the CAF group. Conclusions: Our findings demonstrated that the prevalence of AF as 9.1% in hemodialysis patients, and that AF, especially CAF, were associated with high mortality.
A Syngeneic Orthotopic Murine Model of Pancreatic Adenocarcinoma in the C57/BL6 Mouse Using the Panc02 and 6606PDA Cell Lines
Authors: Partecke L.I. , Sendler M. , Kaeding A. , Weiss F.U. , Mayerle J. , Dummer A. , Nguyen T.D. , Albers N. , Speerforck S. , Lerch M.M. , Heidecke C.D. , von Bernstorff W. , Stier A.
Published: June 2011

Background/Aims: To develop a clinically relevant immunocompetent murine model to study pancreatic cancer using two different syngeneic pancreatic cancer cell lines and to assess MRI for its applicability in this model. Methods: Two cell lines, 6606PDA and Panc02, were employed for the experiments. Cell proliferation and migration were monitored in vitro. Matrigel™ was tested for its role in tumor induction. Tumor cell growth was assessed after orthotopic injection of tumor cells into the pancreatic head of C57/BL6 mice by MRI and histology. Results: Proliferation and migration of Panc02 were significantly faster than those of 6606PDA. Matrigel did not affect tumor growth/migration but prevented tumor cell spread after injection thus avoiding undesired peritoneal tumor growth. MRI could reliably monitor longitudinal tumor growth in both cell lines: Panc02 had a more irregular finger-like growth, and 6606PDA grew more spherically. Both tumors showed local invasiveness. Histologically, Panc02 showed a sarcoma-like undifferentiated growth pattern, whereas 6606PDA displayed a moderately differentiated glandular tumor growth. Panc02 mice had a significantly shorter (28 days) survival than 6606PDA mice (50 days). Conclusion: This model closely mimics human pancreatic cancer. MRI was invaluable for longitudinal monitoring of tumor growth thus reducing the number of mice required. Employing two different cell lines, this model can be used for various treatment and imaging studies.
Thigh Circumference as a Useful Predictor of Body Fat in Adolescent Girls with Anorexia Nervosa
Authors: Konstantynowicz Jerzy , Abramowicz Pawel , Jamiolkowski Jacek , Kadziela-Olech Halina , Bialokoz-Kalinowska Irena , Kierus-Jankowska Karolina , Piotrowska-Jastrzebska Janina , Kaczmarski Maciej
Published: July 2011

Background/Aim: Girls with anorexia nervosa (AN) demonstrate severe depletion of body fat. The aim of this study was to determine an accurate anthropometric measurement for clinical assessment of fat depletion in girls with AN in connection with body composition measured by dual-energy X-ray absorptiometry (DXA). Methods: In 64 female AN patients aged 12.8–23.1 years (mean 16.0 ± 1.8), body mass index (BMI), skinfold thickness (subscapular, abdominal and triceps), mid-upper arm and thigh circumference, fat mass (FM) and lean mass were determined and compared with the data of 71 controls. Results: Girls with AN had lower anthropometric traits and were fat depleted compared to controls (14.9 ± 7.3 vs. 27.4 ± 6.4% of FM using DXA; all p < 0.001). BMI, thigh circumference and subscapular skinfold thickness demonstrated a very similar predictive value for DXA assessment of body fat. Based on the receiver-operating characteristic curve analysis and the determination of the positive predictive value, thigh circumference appeared the most specific and sensitive anthropometric predictor of fatness discriminating between AN and healthy girls, with the AUC value reaching 0.95 (95% CI = 0.92–0.97). Using a cutoff value of 49.6 cm, accuracy was 90.6%, sensitivity 93% and specificity 88.7%. Conclusions: Thigh circumference strongly correlates with DXA-FM and demonstrates a slight clinical advantage over BMI. This simple measurement might also serve as a useful predictor of body fatness in adolescent girls with AN and should therefore be further evaluated in independent cohort studies.
Matrix Metalloproteinase (MMP)-3 Activates MMP-9 Mediated Vascular Smooth Muscle Cell Migration and Neointima Formation in Mice
Authors: Johnson Jason L. , Dwivedi Amrita , Somerville Michelle , George Sarah J. , Newby Andrew C.
Published: July 2011

Objective—

Several matrix metalloproteinases (MMPs) have been implicated in extracellular matrix destruction and other actions that lead to plaque rupture and myocardial infarction. Conversely, other MMPs have been shown to promote vascular smooth muscle cell (VSMC)–driven neointima formation, which contributes to restenosis, fibrous cap formation, and plaque stability. MMP-3 knockout reduced VSMC accumulation in mouse atherosclerotic plaques, implicating MMP-3 in neointima formation. We therefore investigated the effect of MMP-3 knockout on neointima formation after carotid ligation in vivo and VSMC migration in vitro.

Methods and Results—

Twenty-eight days after left carotid ligation, MMP-3 knockout significantly reduced neointima formation (75%,
P
<0.01) compared with wild-type (WT) littermates, and also reduced remodeling of ligated and contralateral carotid arteries. Gelatin zymography illustrated that MMP-3 knockout abolished MMP-9 activation in ligated carotids and scratch-wounded VSMC cultures. MMP-3 knockout also attenuated VSMC migration into a scratch wound by 59% compared with WT cells. Addition of exogenous MMP-3 or activated MMP-9 restored migration of MMP-3 knockouts to that of WT VSMCs, but exogenous MMP-3 had no effect on migration in MMP-9 knockout VSMCs. MMP-9 knockout or knockdown with small interfering RNA significantly retarded VSMC migration to the same extent as MMP-3 knockout.

Conclusion—

These results indicate for the first time that MMP-3 mediated activation of MMP-9 is required for efficient neointima formation after carotid ligation in vivo and for VSMC migration in vitro, whereas MMP-12 plays a redundant role. These findings add to the understanding of MMP action in plaque stability and restenosis.
Vitamin D Deficiency Is Associated With Subclinical Carotid Atherosclerosis
Authors: Carrelli Angela L. , Walker Marcella D. , Lowe Hyesoo , McMahon Don J. , Rundek Tatjana , Sacco Ralph L. , Silverberg Shonni J.
Published: July 2011

Background and Purpose—

The purpose of this study was to assess the association of vitamin D deficiency and indices of mineral metabolism with subclinical carotid markers that predict cardiovascular events.

Methods—

Two hundred three community-dwelling adults (Northern Manhattan Study; age, 68±11; age range, 50 to 93 years) had serum measurements (calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone) and carotid ultrasound (plaque presence, number, maximal carotid plaque thickness, intima-media thickness).

Results—

Adjusting for cardiovascular risk factors, plaque number was associated with phosphorus levels (β=0.39 per 1-mg/dL increase;
P
=0.02) and calcium–phosphorus product (β=0.36 per 10-U increase;
P
=0.03). In those with plaque (N=116 [57%]), the association of plaque number with phosphorus and calcium–phosphorus product persisted. In addition, 25-hydroxyvitamin D was inversely associated with both intima-media thickness (β=−0.01 per 10-ng/mL increase;
P
=0.05) and maximal carotid plaque thickness (β=−0.10 per 10-ng/mL increase;
P
=0.03). In a model containing traditional cardiac risk factors and indices of mineral metabolism, 25-hydroxyvitamin D accounted for 13% of the variance in both intima-media thickness and maximal carotid plaque thickness. Calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were not associated with carotid measures.

Conclusions—

After adjusting for cardiovascular risk factors and renal function, serum phosphorus and calcium–phosphorus product were associated with a greater burden of subclinical carotid atherosclerosis. Low 25-hydroxyvitamin D levels were associated with increased intima-media thickness and maximal carotid plaque thickness in those with plaque, and 25-hydroxyvitamin D contributed in a robust manner to the variance in both. These results confirm and extend data on the association of low vitamin D levels with subclinical carotid atherosclerosis. The precise nature of this association and the optimum levels of vitamin D for vascular health remain to be elucidated.
Blood–Brain Barrier Permeability Abnormalities in Vascular Cognitive Impairment
Authors: Taheri Saeid , Gasparovic Charles , Huisa Branko N. , Adair John C. , Edmonds Elaine , Prestopnik Jillian , Grossetete Mark , Shah N. Jon , Wills John , Qualls Clifford , Rosenberg Gary A.
Published: July 2011

Background and Purpose—

Disruption of the blood–brain barrier has been proposed to be important in vascular cognitive impairment. Increased cerebrospinal fluid albumin and contrast-enhanced MRI provide supporting evidence, but quantification of the blood–brain barrier permeability in patients with vascular cognitive impairment is lacking. Therefore, we acquired dynamic contrast-enhanced MRI to quantify blood–brain barrier permeability in vascular cognitive impairment.

Method—

We studied 60 patients with suspected vascular cognitive impairment. They had neurological and neuropsychological testing, permeability measurements with dynamic contrast-enhanced MRI, and lumbar puncture to measure albumin index. Patients were separated clinically into subcortical ischemic vascular disease (SIVD), multiple and lacunar infarcts, and leukoaraiosis. Twenty volunteers were controls for the dynamic contrast-enhanced MRI studies, and control cerebrospinal fluid was obtained from 20 individuals undergoing spinal anesthesia for nonneurological problems.

Results—

Thirty-six patients were classified as SIVD, 8 as multiple and lacunar infarcts, and 9 as leukoaraiosis. The albumin index was significantly increased in the SIVD group compared with 20 control subjects. Permeabilities for the patients with vascular cognitive impairment measured by dynamic contrast-enhanced MRI were significantly increased over control subjects (
P
<0.05). Patient age did not correlate with either the blood–brain barrier permeability or albumin index. Highest albumin index values were seen in the SIVD group (
P
<0.05) and were significantly increased over multiple and lacunar infarcts. K
i
values were elevated over control subjects in SIVD but were similar to multiple and lacunar infarcts.

Conclusions—

There was abnormal permeability in white matter in patients with SIVD as shown by dynamic contrast-enhanced MRI and albumin index. Future studies will be needed to determine the relationship of blood–brain barrier damage and development of white matter hyperintensities.
On Changing El Niño: A View from Time-Varying Annual Cycle, Interannual Variability, and Mean State
Authors: Qian Cheng , Wu Zhaohua , Fu Congbin , Wang Dongxiao
Published: July 2011

This study investigates changes in the frequency of ENSO, especially the prolonged 1990–95 El Niño event, in the context of secular changes in the annual cycle, ENSO interannual variability, and background mean state of the tropical eastern Pacific sea surface temperature (SST). The ensemble empirical mode decomposition (EEMD) method is applied to isolate those components from the Niño-3 SST index for the period 1880–2008. It is shown that the annual cycle [referred to as a refined modulated annual cycle (MAC)] has strong interannual modulation and secular change in both amplitude and phase: a clear transition from increasing to decreasing amplitude around 1947/48, with both linear trends before and after this turning point statistically significant and the amplitude decreasing by 14% since then, and a significant phase delay trend for the period 1881–1938, but hardly any thereafter. A clear transition from significant deceasing to increasing by about 30% in the amplitude of the ENSO interannual variability around 1937 is also found. When El Niño events are represented as the collective interannual variability, their frequency is found to be almost equivalent to that of La Niña events after 1976. A method for conducting synthetic experiments based on time series analysis further reveals that the apparent prolonged 1990–95 El Niño event was not caused solely by ENSO interannual variability. Rather, the 1991/92 warm period is attributable to an interannual variation superimposed by change in the background mean state; the 1993 warm period is attributable to change in the mean state; and the 1994/95 warm period is attributable to a residual annual cycle, which cannot be fully excluded by a 30-yr mean annual cycle approach. The impact that changing base periods has on the classification of ENSO events and possible solutions is also discussed.
Investigation of Ensemble Variance as a Measure of True Forecast Variance
Authors: Kolczynski Walter C. , Stauffer David R. , Haupt Sue Ellen , Altman Naomi S. , Deng Aijun
Published: July 2011

The uncertainty in meteorological predictions is of interest for applications ranging from economic to recreational to public safety. One common method to estimate uncertainty is by using meteorological ensembles. These ensembles provide an easily quantifiable measure of the uncertainty in the forecast in the form of the ensemble variance. However, ensemble variance may not accurately reflect the actual uncertainty, so any measure of uncertainty derived from the ensemble should be calibrated to provide a more reliable estimate of the actual uncertainty in the forecast. A previous study introduced the linear variance calibration (LVC) as a simple method to determine the ensemble variance to error variance relationship and demonstrated this technique on real ensemble data. The LVC parameters, the slopes, and y intercepts, however, are generally different from the ideal values.

This current study uses a stochastic model to examine the LVC in a controlled setting. The stochastic model is capable of simulating underdispersive and overdispersive ensembles as well as perfectly reliable ensembles. Because the underlying relationship is specified, LVC results can be compared to theoretical values of the slope and y intercept. Results indicate that all types of ensembles produce calibration slopes that are smaller than their theoretical values for ensemble sizes less than several hundred members, with corresponding y intercepts greater than their theoretical values. This indicates that all ensembles, even otherwise perfect ensembles, should be calibrated if the ensemble size is less than several hundred.

In addition, it is shown that an adjustment factor can be computed for inadequate ensemble size. This adjustment factor is independent of the stochastic model and is applicable to any linear regression of error variance on ensemble variance. When applied to experiments using the stochastic model, the adjustment produces LVC parameters near their theoretical values for all ensemble sizes. Although the adjustment is unnecessary when applying LVC, it allows for a more accurate assessment of the reliability of ensembles, and a fair comparison of the reliability for differently sized ensembles.
Multiscale Processes Leading to Supercells in the Landfalling Outer Rainbands of Hurricane Katrina (2005)
Authors: Green Benjamin W. , Zhang Fuqing , Markowski Paul
Published: July 2011

Shallow supercells are frequently observed within the outer rainbands—both onshore and offshore—of landfalling tropical cyclones (TCs). Such supercells can produce tornadoes along the coast even when the center of the parent TC is hundreds of kilometers from land, as was the case with Hurricane Katrina (2005). A convection-permitting simulation with 1.5-km grid spacing in the innermost domain is used in conjunction with radar, radiosonde, and surface observations to investigate the multiscale conditions conducive to supercells in the landfalling outer rainbands of Katrina. Several hours before the eye of the TC made landfall, a baroclinic zone developed along the coast; this front strongly influenced the horizontal distributions of cell-relative helicity and CAPE such that the largest values of these parameters were located over land and water, respectively. An example of a tornadic supercell in the outer rainbands of Katrina is examined. This cell intensified just before landfall and spawned a tornado along the coast, demonstrating the ability of baroclinic boundaries to enhance low-level horizontal vorticity and subsequently intensify updraft rotation within passing cells. Farther inland, the tornadic cell weakened rapidly, suggesting the presence of a narrow coastal zone in which both shear and buoyancy are favorable for tornadogenesis.
Orthodox Theology of Personhood: A Critical Overview (Part 1)
Authors: Lubardić Bogdan
Published: July 2011

This paper offers a critical overview of the theology of personhood which has become one of the distinctive features of Orthodox theology in the 20th Century. A systematised synthesis of traits and elements within this movement is offered, thus rectifying a certain lack of it in current literature. On one hand it is shown that this theology springs forth from the neo-patristic ‘turn’ of Orthodox theology. On the other hand it is demonstrated how theoretical instances of this ‘turn’ bear upon, and appear within the model of the conception of personhood: in its Trinitarian, Christological, ecclesiological and anthropological dimensions. It is this model of personhood, in its basic elements and connections, which is at work in the ongoing debate on the human person in the Orthodox Church. The model of personhood and the model of eucharistic, i.e. ecclesial self-understanding of the Church are shown to implicate each other intrinsically.
Spiritual Sobriety in 1 Peter
Authors: Watson David F.
Published: July 2011

1 Peter encourages believers to adhere to Christian teachings, community, and norms of behavior in the face of suffering and conflict with the dominant culture. In 1 Peter's schema, Christians suffer largely because non-Christians are unaware of God's saving work in Jesus Christ and the special status that God has bestowed upon the faithful. In three instances (1:13; 4:7; 5:8), 1 Peter calls believers to “be sober.” These are not simply exhortations to be alert in light of the coming judgment. Those who are sober know of the salvation offered to them in Jesus Christ and base their hope on it. They view their circumstances in light of the truths of their faith, and therefore see the world around them differently than those who do not share their beliefs. The exhortation to sobriety, then, is not just a call to action, but to proper belief. Their worldview as Christians is the basis of their motivation to remain both in association and conduct within the Christian community. Christians today can take from these admonitions the reminder that the truths of our faith precede the living out of our faith. Catechesis precedes mission. Knowledge of the truths of our faith is part of what forms our view of the world and helps us to live as we should.
Revenue, rent…profit? Early British imperialism1, political economy and the search for a differentia specifica (inter se)
Authors: Govind Rahul
Published: July 2011

This article argues that in the mid to late eighteenth century, political economy, through writers such as Francois Quesnay, David Hume and Adam Smith, saw a discussion of ‘despotism’, which stood for thinking through the political arrangement within which economic productivity was formulated; even as the distinction between the two was not always self-evident. This theoretical function of despotism disappears in the ‘mature’ phase of political economy (David Ricardo), precisely when it was taking shape—in institutional and conceptual-lexical terms—in the subcontinent through Britain’s conquest of India via the East India Company. We argue that the disappearance of despotism at the conceptual level in this phase in Britain is not only questionable from a theoretical standpoint but also played its historical role as a decoy in occluding attention toward imperialism in India wherein the distinction between the political and the economic was becoming more and more difficult to make. Through such an investigation we thus hope to examine the emergence of the economy (and by implication the state-political) as an independent analytic site as well as evaluate its categories and historical significance. We base our argument on a reading of the canonical texts of figures such as Adam Smith, William Blackstone and David Ricardo, Land Revenue Settlement sources in India and the hitherto neglected economic writings of W.H. Sleeman.