bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Mumps Viruses Circulating in Mongolia: Identification of a Novel Cluster of Genotype H
Authors: Kidokoro Minoru , Tuul Rentsengiin , Komase Katsuhiro , Nymadawa Pagbajab
Published: March 2011

Although mumps virus is still causing annual epidemics in Mongolia, very few epidemiological and virological data have been reported. We describe here the first phylogenetic analysis data on the mumps viruses circulated in Mongolia in 2009. We detected 21 mumps virus cDNAs and obtained a virus isolate from 32 throat swabs of mumps patients in Ulaanbaatar, the capital of Mongolia. The phylogenetic analyses based on the 316 nucleotides of the small hydrophobic gene show that these sequences form a single cluster, with the closest relatedness to the viruses belonging to genotype H. According to the recommendation of the World Health Organization, Mongolian mumps viruses could be classified into a novel genotype because the divergence between new sequences and genotype H reference viruses is >5% (6.3 to 8.2%). However, additional analyses based on the fusion gene, the hemagglutinin-neuraminidase gene, and the whole-genome indicate that the divergences between the Mongolian isolate and other genotype H strains never exceed the within-genotype divergences of other genotypes. These results suggest that Mongolia strains should be included in genotype H and that the current criteria for mumps virus genotyping should be revised. We propose here that the Mongolian viruses should be classified as a new subgenotype termed H3. Since previous epidemiological studies suggested that genotypes H may be associated with central nervous system diseases, we evaluated the neurovirulence of the Mongolian isolate in the neonatal rat system. However, the virus does not exhibit prominent neurovirulence in rats.
Systemic Dissemination of H5N1 Influenza A Viruses in Ferrets and Hamsters after Direct Intragastric Inoculation
Authors: Shinya Kyoko , Makino Akiko , Tanaka Hiroji , Hatta Masato , Watanabe Tokiko , Le Mai Q. , Imai Hirotaka , Kawaoka Yoshihiro
Published: March 2011

Although oral exposure to H5N1 highly pathogenic avian influenza viruses is a risk factor for infection in humans, it is unclear how oral exposure to these virus results in lethal respiratory infections. To address this issue, we inoculated ferrets and hamsters with two highly pathogenic H5N1 strains. These viruses, inoculated directly into the stomach, were isolated from the large intestine and the mesenteric lymph nodes within 1 day of inoculation and subsequently spread to multiple tissues, including lung, liver, and brain. Histopathologic analysis of ferrets infected with virus via direct intragastric inoculation revealed lymph folliculitis in the digestive tract and mesenteric lymph nodes and focal interstitial pneumonia. Comparable results were obtained with the hamster model. We conclude that, in mammals, ingested H5N1 influenza viruses can disseminate to nondigestive organs, possibly through the lymphatic system of the gastrointestinal tract.
Natural Killer Cells Recognize Friend Retrovirus-Infected Erythroid Progenitor Cells through NKG2D–RAE-1 Interactions In Vivo
Authors: Ogawa Tatsuya , Tsuji-Kawahara Sachiyo , Yuasa Takae , Kinoshita Saori , Chikaishi Tomomi , Takamura Shiki , Matsumura Haruo , Seya Tsukasa , Saga Toshihiko , Miyazawa Masaaki
Published: March 2011

Natural killer (NK) cells function as early effector cells in the innate immune defense against viral infections and also participate in the regulation of normal and malignant hematopoiesis. NK cell activities have been associated with early clearance of viremia in experimental simian immunodeficiency virus and clinical human immunodeficiency virus type 1 (HIV-1) infections. We have previously shown that NK cells function as major cytotoxic effector cells in vaccine-induced immune protection against Friend virus (FV)-induced leukemia, and NK cell depletion totally abrogates the above protective immunity. However, how NK cells recognize retrovirus-infected cells remains largely unclear. The present study demonstrates a correlation between the expression of the products of retinoic acid early transcript-1 (RAE-1) genes in target cells and their susceptibility to killing by NK cells isolated from FV-infected animals. This killing was abrogated by antibodies blocking the NKG2D receptorin vitro. Further, the expression of RAE-1 proteins on erythroblast surfaces increased early after FV inoculation, and administration of an RAE-1-blocking antibody resulted in increased spleen infectious centers and exaggerated pathology, indicating that FV-infected erythroid cells are recognized by NK cells mainly through the NKG2D–RAE-1 interactionsin vivo. Enhanced retroviral replication due to host gene-targeting resulted in markedly increased RAE-1 expression in the absence of massive erythroid cell proliferation, indicating a direct role of retroviral replication in RAE-1 upregulation.
ON POSITIVELY CURVED FOUR-MANIFOLDS WITH S1-SYMMETRY
Authors: KIM JIN HONG
Published: March 2011

It is well known by the work of Hsiang and Kleiner that every closed oriented positively curved four-dimensional manifold with an effective isometric S1-action is homeomorphic to S4or CP2. As stated, it is a topological classification. The primary goal of this paper is to show that it is indeed a diffeomorphism classification for such four-dimensional manifolds. The proof of this diffeomorphism classification also shows an even stronger statement that every positively curved simply connected four-manifold with an isometric circle action admits another smooth circle action which extends to a two-dimensional torus action and is equivariantly diffeomorphic to a linear action on S4or CP2. The main strategy is to analyze all possible topological configurations of effective circle actions on simply connected four-manifolds by using the so-called replacement trick of Pao.
CHAOS IN SANDPILE MODELS
Authors: MOGHIMI-ARAGHI SAMAN , MOLLABASHI ALI
Published: March 2011

We have investigated the "weak chaos" exponent to see if it can be considered as a classification parameter of different sandpile models. Our simulation results show that the (Abelian) BTW sandpile model, the (non-Abelian) Zhang model, and the ("Abelian") Manna model possesses different "weak chaos" exponents, so they may belong to different universality classes. Finally, we show that getting off the critical point destroys this behavior in these models.
TEPE
Authors: Knorreck Daniel , Apvrille Ludovic , de Saqui-Sannes Pierre
Published: March 2011

Using UML or SysML models in a verification-centric method requires a property expression language, a formal semantics, and a tool. The paper introduces TEPE, a graphical TEmporal Property Expression language based on SysML parametric diagrams. TEPE enriches the expressiveness of other common property languages in particular with the notion of physical time and unordered signal reception. TEPE is further instantiated in the AVATAR real-time UML profile. TTool, an open-source toolkit, implements a press-button approach for the formal verification of AVATAR-TEPE properties with UPPAAL. An elevator system serves as example
Spelling Correction for Dialectal Arabic Dictionary Lookup
Authors: Rytting C. Anton , Zajic David M. , Rodrigues Paul , Wayland Sarah C. , Hettick Christian , Buckwalter Tim , Blake Charles C.
Published: March 2011

The “Did You Mean...?” system, described in this article, is a spelling corrector for Arabic that is designed specifically for L2 learners of dialectal Arabic in the context of dictionary lookup. The authors use an orthographic density metric to motivate the need for a finer-grained ranking method for candidate words than unweighted Levenshtein edit distance. The Did You Mean...? architecture is described, and the authors show that mean reciprocal rank can be improved by tuning operation weights according to sound confusions, and by anticipating likely spelling variants.
Interruption Point Detection of Spontaneous Speech Using Inter-Syllable Boundary-Based Prosodic Features
Authors: Wu Chung-Hsien , Liang Wei-Bin , Yeh Jui-Feng
Published: March 2011

This article presents a probabilistic scheme for detecting the interruption point (IP) in spontaneous speech based on inter-syllable boundary-based prosodic features. Because of the high error rate in spontaneous speech recognition, a combined acoustic model considering both syllable and subsyllable recognition units, is firstly used to determine the inter-syllable boundaries and output the recognition confidence of the input speech. Based on the finding that IPs always occur at inter-syllable boundaries, a probability distribution of the prosodic features at the current potential IP is estimated. The Conditional Random Field (CRF) model, which employs the clustered prosodic features of the current potential IP and its preceding and succeeding inter-syllable boundaries, is employed to output the IP likelihood measure. Finally, the confidence of the recognized speech, the probability distribution of the prosodic features and the CRF-based IP likelihood measure are integrated to determine the optimal IP sequence of the input spontaneous speech. In addition, pitch reset and lengthening are also applied to improve the IP detection performance. The Mandarin Conversional Dialogue Corpus is adopted for evaluation. Experimental results show that the proposed IP detection approach obtains 10.56% and 6.5% more effective results than the hidden Markov model and the Maximum Entropy model respectively under the same experimental conditions. Besides, the IP detection error rate can be further reduced by 9.15% using pitch reset and lengthening information. The experimental results confirm that the proposed model based on inter-syllable boundary-based prosodic features can effectively detect the interruption point in spontaneous Mandarin speech.
Output privacy in data mining
Authors: Wang Ting , Liu Ling
Published: March 2011

Privacy has been identified as a vital requirement in designing and implementing data mining systems. In general, privacy preservation demands protecting both
input
and
output
privacy: the former refers to sanitizing the raw data itself before performing mining; while the latter refers to preventing the mining output (models or patterns) from malicious inference attacks. This article presents a systematic study on the problem of protecting output privacy in data mining, and particularly, stream mining: (i) we highlight the importance of this problem by showing that even sufficient protection of input privacy does not guarantee that of output privacy; (ii) we present a general inferencing and disclosure model that exploits the intrawindow and interwindow privacy breaches in stream mining output; (iii) we propose a light-weighted countermeasure that effectively eliminates these breaches without explicitly detecting them, while minimizing the loss of output accuracy; (iv) we further optimize the basic scheme by taking account of two types of semantic constraints, aiming at maximally preserving utility-related semantics while maintaining hard privacy guarantee; (v) finally, we conduct extensive experimental evaluation over both synthetic and real data to validate the efficacy of our approach.
Query-preserving watermarking of relational databases and Xml documents
Authors: Gross-AMBLARD David
Published: March 2011

Watermarking allows robust and unobtrusive insertion of information in a digital document. During the last few years, techniques have been proposed for watermarking relational databases or Xml documents, where information insertion must preserve a specific measure on data (for example the mean and variance of numerical attributes).

In this article we investigate the problem of watermarking databases or Xml while preserving a set of parametric queries in a specified language, up to an acceptable distortion. We first show that unrestricted databases can not be watermarked while preserving trivial parametric queries. We then exhibit query languages and classes of structures that allow guaranteed watermarking capacity, namely 1) local query languages on structures with bounded degree Gaifman graph, and 2) monadic second-order queries on trees or treelike structures. We relate these results to an important topic in computational learning theory, the VC-dimension. We finally consider incremental aspects of query-preserving watermarking.
Determination of Surface Exchange Coefficients of LSM, LSCF, YSZ, GDC Constituent Materials in Composite SOFC Cathodes
Authors: Armstrong E. N. , Duncan K. L. , Oh D. J. , Weaver J. F. , Wachsman E. D.
Published: March 2011

A novel approach to processing and modeling isothermal isotope exchange (IIE) data was developed to extract kinetic rate coefficients for the oxygen reduction reaction (ORR) on cathode materials used for solid oxide fuel cells (SOFC). IIE is capable of testing powders with particle sizes on the nano-scale, where the effective sample thickness (particle size) was shown to be below the characteristic thickness (Lc) for ionically conducting materials. This allows for accurate kinetic measurements in surface exchange controlled regimes, in contrast to secondary ion mass spectrometry depth profiling and electrical conductivity relaxation techniques where sample thicknesses are typically in the diffusion limited or mixed regimes. Surface exchange coefficients (k*) were extracted and Lc values calculated from cathode (La0.6Sr0.4)(Co0.2Fe0.8)O3–δ (LSCF) and (La0.8Sr0.2)MnO3 (LSM), and electrolyte (Ce0.9Gd0.1)O2–δ (GDC) and (Zr0.8Y0.2)O2 (YSZ) materials. Additionally, diffusion coefficients (D*) were extracted for LSM. In a surface exchange controlled regime LSCF exhibits a low activation energy for k*, while for LSM k* was observed to increase with decreasing temperature consistent with a precursor-mediated mechanism in which there is a negative apparent activation energy for the dissociative chemisorption of O2. GDC was shown to exhibit a low activation energy for k*, lower than YSZ, which is attributed to higher concentration of electrons in GDC than YSZ.
13C Solid State NMR Suggests Unusual Breakdown Products in SEI Formation on Lithium Ion Electrodes
Authors: Leifer N. , Smart M. C. , Prakash G. K. S. , Gonzalez L. , Sanchez L. , Smith K. A. , Bhalla P. , Grey C. P. , Greenbaum S. G.
Published: March 2011

This study investigates the organic components of the solid electrolyte interphase (SEI) on the carbonaceous anodic electrode in LiCoO2batteries using solid-state nuclear magnetic resonance (NMR) techniques. The electrolyte solvents, ethylene carbonate and diethyl carbonate, were enriched on the carbonyl carbon prior to cell assembly and conditioning in an attempt to trace the breakdown pathways of these components. A strong signal was seen, demonstrating that the carbonyl carbons of both electrolytes survive in some reasonable quantity as insoluble breakdown products on the rinsed electrode surface. This confirms that the fate of these carbons as consumed in the formation of CO2is either not unique, or not as final product. Furthermore the central carbonyl carbon survives, not as an intact carbonyl species, but instead in the form of compounds in which the carbon-oxygen double bond has been disrupted. Formation of this class of species is likely initiated by a nucleophilic attack on the carbonyl carbon by one or more radical, alkoxy, carbanion or fluorine-containing ionic species formed from solvent and/or salt breakdown. These results suggest a new family of electrolyte breakdown products, predominantly consisting of binary, tertiary and/or quaternary ether-type compounds (i.e., orthocarbonates and orthoesters), as well as fluorine-containing alkoxy compounds.
Chronic estradiol-17β exposure increases superoxide production in the rostral ventrolateral medulla and causes hypertension: reversal by resveratrol
Authors: Subramanian Madhan , Balasubramanian Priya , Garver Hannah , Northcott Carrie , Zhao Huawei , Haywood Joseph R. , Fink Gregory D. , MohanKumar Sheba M. J. , MohanKumar P. S.
Published: March 2011

Women are exposed to estrogen in several forms, such as oral contraceptive pills and hormone replacement therapy. Although estrogen was believed to be cardioprotective, lately, its beneficial effects are being questioned. Recent studies indicate that oxidative stress in the rostral ventrolateral medulla (RVLM) may play a role in the development of hypertension. Therefore, we hypothesized that chronic exposure to low levels of estradiol-17β (E2) leads to hypertension in adult-cycling female Sprague Dawley (SD) rats potentially through generation of superoxide in the RVLM. To test this hypothesis, young adult (3 or 4 mo old) female SD rats were either sham-implanted or implanted (subcutaneously) with slow-release E2pellets (20 ng/day) for 90 days. A group of control and E2-treated animals were fed lab chow or chow containing resveratrol (0.84 g/kg of chow), an antioxidant. Rats were implanted with telemeters to continuously monitor blood pressure (BP) and heart rate (HR). At the end of treatment, the RVLM was isolated for measurements of superoxide. E2treatment significantly increased mean arterial pressure (mmHg) and HR (beats/min) compared with sham rats (119.6 ± 0.8 vs. 105.1 ± 0.7 mmHg and 371.7 ± 1.5 vs. 354.4 ± 1.3 beats/min, respectively; P < 0.0001). Diastolic and systolic BP were significantly increased in E2-treated rats compared with control animals. Superoxide levels in the RVLM increased significantly in the E2-treated group (0.833 ± 0.11 nmol/min·mg) compared with control (0.532 ± 0.04 nmol/min·mg; P < 0.05). Treatment with resveratrol reversed the E2-induced increases in BP and superoxide levels in the RVLM. In conclusion, these findings support the hypothesis that chronic exposure to low levels of E2induces hypertension and increases superoxide levels in the RVLM and that this effect can be reversed by resveratrol treatment.
(Pro)renin promotes fibrosis gene expression in HEK cells through a Nox4-dependent mechanism
Authors: Clavreul Nicolas , Sansilvestri-Morel Patricia , Magard Delphine , Verbeuren Tony J. , Rupin Alain
Published: March 2011

The (pro)renin receptor (PRR) has recently been demonstrated to bind equally well renin and its precursor, prorenin, leading to a similar intracellular signaling independent of angiotensin II. In this study, we report that human embryonic kidney cells (HEK) exposed to renin or prorenin for 24 h in the presence of a blocking concentration of the angtiotensin-converting enzyme inhibitor perindoprilate increased superoxide anion production as measured by luminescence (lucigenin) and electron spin resonance spectroscopy (hydroxylamine radical transition). Also, both renin and prorenin increased Nox4 expression while Nox2, p47phox, and p67phox remained unchanged. In an investigation of the effects of renin and prorenin on fibrosis genes, it appeared that both proteins stimulated transforming growth factor-β (TGF-β), fibronectin, and plasminogen activator inhibitor type 1 (PAI-1) expression and therefore participated to an overall switch toward a profibrotic state of the kidney cells. When the cells were transfected with a siRNA targeting the PRR, Nox4 expression was efficiently prevented as well as the increase in superoxide production, TGF-β, fibronectin, and PAI-1. Finally, we demonstrated that transfection of the cells with a Nox4-specific small interfering (si) RNA also prevented fibrosis gene expression following treatment with renin or prorenin. The results demonstrate that renin and prorenin, through their specific membrane receptor and independently of angiotensin II, promote fibrosis gene expression via a Nox4-dependent mechanism.
Contribution of cells in the posterior parietal cortex to the planning of visually guided locomotion in the cat: effects of temporary visual interruption
Authors: Marigold Daniel S. , Drew Trevor
Published: March 2011

In the present study, we determined whether cells in the posterior parietal cortex (PPC) may contribute to the planning of voluntary gait modifications in the absence of visual input. In two cats we recorded the responses of 41 neurons in layer V of the PPC that discharged in advance of the gait modification to a 900-ms interruption of visual information (visual occlusion). The cats continued to walk without interruption during the occlusion, which produced only minimal changes in step cycle duration and paw placement. Visual occlusion applied during the period of cell discharge was without significant effect on discharge frequency in 57% of cells. In the other cells, the visual occlusion produced either significant decreases (18%) or increases (21%) of discharge activity (in 1 cell there was both an increase and a decrease). The mean latency of the changes was 356 ms for decreases and 252 ms for increases. In most neurons, discharge frequency, when modified, returned to the same levels as during unoccluded locomotion when vision was restored. In some cells, there were significant changes in discharge activity after the restoration of vision; these were associated with corrections of gait. These results suggest that the PPC is more involved in the visuomotor transformations necessary to plan gait modifications than in continual sensory processing of visual information. We further propose that cells in the PPC contribute both to the planning of gait modifications on the basis of only intermittent visual sampling and to visually guided online corrections of gait.
Renewable Energy Driven by Le Chatelier's Principle, Enzyme Function, and Non-Additive Contributions to Ion Fluctuations: A Hypothesis in Biomechanical and Nanotechnology Energy Theory
Authors: Manzetti Sergio
Published: March 2011

The search for green energy sources has populated the research arena with significant emphasis on green electronics, green fuels, and green batteries that reduce waste, emissions, and environmental toxicity. Simultaneously, nanotechnology has developed substantially in the recent years and the emerging area of nanoenergetics has shown impressive discoveries that can aid in the search for alternative and green energies. The use of exotic materials in these fields and even enzymes has led scientists to be able to cross-link biomolecules and nanotechnology circuits, which can be important points in the search of novel energy searches. This paper discusses a biochemical energy-generating unit driven by ion fluctuations and spontaneous enzyme conformational changes. The paper lays also the theoretical thermodynamical foundation of the nanoenergy unit and to exploit the principle of nonadditivity and equilibrium as main forces in driving an energy-generating reaction.
Same Surgeon: Different Centre Equals Differing Lymph Node Harvest following Colorectal Cancer Resection
Authors: Evans M. D. , Robinson S. , Badiani S. , Rees A. , Stamatakis J. D. , Karandikar S. S. , Langman G.
Published: March 2011

Introduction. The aim of this study was to examine the effect of surgeon relocation on lymph node (LN) retrieval in colorectal cancer (CRC) resection.Methods. The study population was 213 consecutive patients undergoing CRC resection by a single surgeon, at two units: unit one 110 operations (2002–2005) and unit two 103 (2005–2009). LN yields and case mix were compared.Results. Median LN harvests were significantly different between the two centres: unit 1: 13 nodes/patient and unit 2: 22 nodes/patient (). In unit one 42% of cases were LN positive and in unit two 48% (). There was no difference in case mix. Multivariate analysis identified unit () and pathologist () as independent predictors of harvest.Conclusions. A surgeon moving units can experience significantly different LN yield following CRC resection. Both units comply with national standards, but the “surgeon's results” at the two units appear to be pathologist dependent. This has implications for nodal harvest as a surrogate marker of surgical quality.
Smoking, Alcohol, and Betel Quid and Oral Cancer: A Prospective Cohort Study
Authors: Lin Wen-Jiun , Jiang Rong-San , Wu Shang-Heng , Chen Fun-Jou , Liu Shih-An
Published: March 2011

We aimed to investigate the association between smoking, alcoholic consumption, and betel quid chewing with oral cancer in a prospective manner. All male patients age ≥18 years who visited our clinic received an oral mucosa inspection. Basic data including personal habits were also obtained. A multivariate logistic regression model was utilized to determine relevant risk factors for developing oral cavity cancer. A total of 10,657 participants were enrolled in this study. Abnormal findings were found in 514 participants (4.8%). Three hundred forty-four participants received biopsy, and 230 patients were proven to have oral cancer. The results of multivariate logistic regression found that those who smoked, consumed alcohol, and chewed betel quid on a regular basis were most likely to develop cancer (odds ratio: 46.87, 95% confidence interval: 31.84–69.00). Therefore, habitual cigarette smokers, alcohol consumers, and betel quid chewers have a higher risk of contracting oral cancer and should receive oral screening regularly so potential oral cancer can be detected as early as possible.
Garlic Constituent Diallyl Trisulfide Suppresses X-linked Inhibitor of Apoptosis Protein in Prostate Cancer Cells in Culture andIn Vivo
Authors: Kim Su-Hyeong , Bommareddy Ajay , Singh Shivendra V.
Published: March 2011

We have shown previously that garlic constituent diallyl trisulfide (DATS) inhibits growth of cultured and xenografted human prostate cancer cells in association with apoptosis induction, but the mechanism of cell death is not fully understood. The present study systematically investigates the role of inhibitor of apoptosis (IAP) family proteins in the regulation of DATS-induced apoptosis using cultured PC-3 and LNCaP human prostate cancer cells and dorsolateral prostate from control and DATS-treated transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Level of X-linked inhibitor of apoptosis (XIAP) protein was decreased on 8-hour treatment with 20 and 40 μmol/L DATS, but this effect was partially attenuated at the 16-hour time point. DATS-mediated decline in XIAP protein level was partially reversible in the presence of proteasomal inhibitor MG132. In contrast, DATS-treated PC-3 and LNCaP cells exhibited marked induction of survivin and cellular inhibitor of apoptosis protein 1 (cIAP1) proteins. Induction of survivin protein expression resulting from DATS exposure was associated with an increase in its mRNA level. Dorsolateral prostates from DATS-treated TRAMP mice exhibited statistically significant downregulation of XIAP and induction of survivin protein compared with those of control mice. Ectopic expression of XIAP conferred partial but significant protection against DATS-induced apoptosis. On the other hand, DATS-induced apoptosis was only marginally affected by RNA interference of survivin or cIAP1. In conclusion, the present study indicates that the DATS-induced apoptosis in prostate cancer cells is mediated in part by suppression of XIAP protein expression, and that XIAP represents a viable biomarker of DATS response for future clinical investigations. Cancer Prev Res; 4(6); 897–906. ©2011 AACR.
Fabry’s Disease and Psychosis: Causality or Coincidence?
Authors: Gairing S. , Wiest R. , Metzler S. , Theodoridou A. , Hoff P.
Published: March 2011

A 21-year-old female with Fabry’s disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.
Short-Term Motor Compensations to Denervation of Feline Soleus and Lateral Gastrocnemius Result in Preservation of Ankle Mechanical Output during Locomotion
Authors: Prilutsky Boris I. , Maas Huub , Bulgakova Margarita , Hodson-Tole Emma F. , Gregor Robert J.
Published: March 2011

Denervation of selected ankle extensors in animals results in locomotor changes. These changes have been suggested to permit preservation of global kinematic characteristics of the hindlimb during stance. The peak ankle joint moment is also preserved immediately after denervation of several ankle extensors in the cat, suggesting that the animal’s response to peripheral nerve injury may also be aimed at preserving ankle mechanical output. We tested this hypothesis by comparing joint moments and power patterns during walking before and after denervation of soleus and lateral gastrocnemius muscles. Hindlimb kinematics, ground reaction forces and electromyographic activity of selected muscles were recorded during level, downslope (–50%) and upslope (50%) walking before and 1–3 weeks after nerve denervation. Denervation resulted in increased activity of the intact medial gastrocnemius and plantaris muscles, greater ankle dorsiflexion, smaller knee flexion, and the preservation of the peak ankle moment during stance. Surprisingly, ankle positive power generated in the propulsion phase of stance was increased (up to 50%) after denervation in all walking conditions (p < 0.05). The obtained results suggest that the short-term motor compensation to denervation of lateral gastrocnemius and soleus muscles may allow for preservation of mechanical output at the ankle. The additional mechanical energy generated at the ankle during propulsion can result, in part, from increased activity of intact synergists, the use of passive tissues around the ankle and by the tendon action of ankle two-joint muscles and crural fascia.
Reduced-Intensity Conditioning Regimen Combined with Low-Dose Total Body Irradiation in the Treatment of Myelodysplastic Syndrome
Authors: Lee Sung-Eun , Lim Jihyang , Yahng Seung-Ah , Cho Byung-Sik , Eom Ki-Seong , Kim Myungshin , Kim Yoo-Jin , Kim Hee-Je , Min Chang-Ki , Lee Seok , Kim Dong-Wook , Lee Jong-Wook , Min Woo-Sung , Park Chong-Won , Cho Seok-Goo
Published: March 2011

Although reduced-intensity conditioning (RIC) has been increasingly used in patients with myelodysplastic syndrome (MDS) to reduce transplant-related mortality, a high relapse rate in RIC remains an unresolved problem. Considering the additive antileukemic effect of low-dose total body irradiation (TBI), we evaluated the feasibility of combining RIC regimens with low-dose TBI in de novo MDS. The RIC regimen combined with low-dose TBI in this study consisted of fludarabine (150 mg/m2), intravenous busulfan (6.4 mg/kg), and TBI (400 cGy). Antithymocyte globulin was used to overcome HLA mismatching. A total of 31 subjects were recruited with a median age of 39 years (range 19–63). The patients received transplants from siblings (n = 20) or unrelated donors (n = 11). All patients rapidly achieved full-donor chimerism. At a median follow-up for survivors of 35 months (range 6.0–54.9), the 3-year overall survival, event-free survival, transplantation-related mortality, and relapse rates were 67.6, 63.2, 20.5 and 11.4%, respectively. The 3-year cumulative incidence of acute (grades II–IV) and chronic extensive graft-versus-host disease in patients who survived at least 100 days was 39.2 and 44.6%, respectively. These results suggest that an RIC combined with low-dose TBI may be a feasible therapeutic approach for treating de novo MDS.
Methylation Status of Imprinted Genes and Repetitive Elements in Sperm DNA from Infertile Males
Authors: El Hajj N. , Zechner U. , Schneider E. , Tresch A. , Gromoll J. , Hahn T. , Schorsch M. , Haaf T.
Published: March 2011

Stochastic, environmentally and/or genetically induced disturbances in the genome-wide epigenetic reprogramming processes during male germ-cell development may contribute to male infertility. To test this hypothesis, we have studied the methylation levels of 2 paternally (H19 and GTL2) and 5 maternally methylated (LIT1, MEST, NESPAS, PEG3, and SNRPN) imprinted genes, as well as of ALU and LINE1 repetitive elements in 141 sperm samples, which were used for assisted reproductive technologies (ART), including 106 couples with strictly male-factor or combined male and female infertility and 28 couples with strictly female-factor infertility. Aberrant methylation imprints showed a significant association with abnormal semen parameters, but did not seem to influence ART outcome. Repeat methylation also differed significantly between sperm samples from infertile and presumably fertile males. However, in contrast to imprinted genes, ALU methylation had a significant impact on pregnancy and live-birth rate in couples with male-factor or combined infertility. ALU methylation was significantly higher in sperm samples leading to pregnancy and live-birth than in those that did not. Sperm samples leading to abortions showed significantly lower ALU methylation levels than those leading to the birth of a baby.
Androgen Receptor Mutations Are Associated with Altered Epigenomic Programming as Evidenced by HOXA5 Methylation
Authors: Bens S. , Ammerpohl O. , Martin-Subero J.I. , Appari M. , Richter J. , Hiort O. , Werner R. , Riepe F.G. , Siebert R. , Holterhus P.-M.
Published: March 2011

Male external genital differentiation is accompanied by implementation of a long-term, male-specific gene expression pattern indicating androgen programming in cultured genital fibroblasts. We hypothesized the existence of an epigenetic background contributing to this phenomenon. DNA methylation levels in 2 normal scrotal fibroblast strains from 46,XY males compared to 2 labia majora fibroblast strains from 46,XY females with complete androgen insensitivity syndrome (AIS) due to androgen receptor (AR) mutations were analyzed by Illumina GoldenGate methylation arrays®. Results were validated with pyrosequencing in labia majora fibroblast strains from fifteen 46,XY patients and compared to nine normal male scrotal fibroblast strains. HOXA5 showed a significantly higher methylation level in complete AIS. This finding was confirmed by bisulfite pyrosequencing of 14 CpG positions within the HOXA5 promoter in the same strains. Extension of the 2 groups revealed a constant low HOXA5 methylation pattern in the controls in contrast to a highly variable methylation pattern in the AIS patients. HOXA5 represents a candidate gene of androgen-mediated promoter methylation. The constantly low HOXA5 DNA methylation level of normal male scrotal fibroblast strains and the frequently high methylation levels in labia majora fibroblast strains in AIS indicate for the first time that androgen programming in sexual differentiation is not restricted to global gene transcription but also occurs at the epigenetic level.
Testicular Gene Expression in Cryptorchid Boys at Risk of Azoospermia
Authors: Hadziselimovic F. , Hadziselimovic N.O. , Demougin P. , Oakeley E.J.
Published: March 2011

Despite timely and successful surgery, 32% of patients with bilateral and 10% with unilateral cryptorchidism will develop azoospermia. Cryptorchid boys at risk of azoospermia display a typical testicular histology of impaired mini-puberty at the time of the orchidopexy. During mini-puberty increased gonadotropin and testosterone secretion stimulate transformation of gonocytes into Ad spermatogonia. In the azoospermia risk group this transformation is to a great extent impaired. This study aimed to analyze data on whole genome expression signatures of undescended testes at risk of developing azoospermia. Twenty-three testicular biopsies from 22 boys were analyzed (19 testes from 18 boys with cryptorchidism and 4 contralateral descended testes from patients with testicular agenesis). Expression profiling identified 483 genes not or under-expressed in the azoospermia risk group compared with the control and low risk for azoospermia (LAZR) groups. Annotated loci were associated with spermatogenesis. Other significant genes were cellular defense response genes and hormone-controlled loci involved in spermatogenesis. Some genes transcribed in normal adult meiotic and post-meiotic germ cells are activated in healthy juvenile Ad spermatogonia. Thus, molecular events initiating the testicular expression program at the onset of puberty and maintaining it during adulthood occur very early in prepubertal testes. This molecular event is to a great extent impaired in the high risk for azoospermia (HAZR) group lacking Ad spermatogonia (stem cells for spermatozoa) indicating impaired mini-puberty.
The Role of the Immunogenetic Background in the Development and Recurrence of Acute Idiopathic Pericarditis
Authors: Lazaros George , Karavidas Apostolos , Spyropoulou Maria , Tsiachris Dimitrios , Halapas Antonios , Zacharoulis Achilleas , Arapi Sophia , Matzaraki Vasiliki , Papadopoulos Kostantinos , Korres Dimitrios , Iniotaki Aliki , Pyrgakis Vlassis , Stefanadis Christodoulos
Published: March 2011

Objectives: We assessed the role of the immunogenetic background in the development and recurrence of acute idiopathic pericarditis (AIP). Methods: Fifty-five patients with a first episode of AIP were followed for 23.8 ± 6.3 months and recurrences were recorded. The control group consisted of 246 healthy individuals. In all subjects, genomic human leukocyte antigen (HLA) typing was performed. Moreover, circulating lymphocyte subpopulations were studied in 44 randomly selected patients and in 20 controls. Results: An increased frequency of HLA-A*02, -Cw*07 and -DQB1*0202 alleles, and a decreased frequency of the -DQB1*0302 allele was detected in patients with AIP. The recurrence rate was 40% and time to recurrence was 202.8 ± 164.1 days. In patients with idiopathic recurrent pericarditis (RP), increased frequencies of HLA-A*02, -Cw*07 and -DQB1*0202 alleles were found. Notably, no patient with RP exhibited HLA-DRB1*04 and -DQB1*0302 alleles. Patients with RP exhibited lower CD4+/CD45RA+ naïve T cells (p = 0.03) than controls, and higher CD8+DR+ activated T cells (p = 0.01) than patients without recurrence and controls. Conclusions: HLA alleles may confer either susceptibility or resistance to AIP and RP. Circulating T-cell subpopulations may also predict RP. A combination of the above parameters might help to better define patients prone to recurrence.
Natural History of Mitral Valve Prolapse in Military Aircrew
Authors: Wand Ori , Prokupetz Alex , Grossman Alon , Assa Amit
Published: March 2011

Objective: Mitral valve prolapse (MVP) is a common cardiac abnormality whose natural history differs among various patient populations. High-performance flight is associated with exposure to varying acceleration forces and strenuous isometric physical activity. The effect of the military flying environment on the natural history and progression of MVP is poorly defined. Methods: We evaluated a cohort which included all military aviators in the Israeli Air Force diagnosed with MVP. Medical records and echocardiographic studies of participants were reviewed for the development of clinical or echocardiographic complications. Results: The study population was comprised of 24 aviators, 14 of whom were high-performance aviators. Average follow-up was 23.5 years (total 563 person-years). Four aviators suffered from MVP-related complications including 2 cases of flail valve due to chordae rupture and 1 case each of newly diagnosed atrial fibrillation and infective endocarditis. Progression of asymptomatic mitral regurgitation was identified in 11 aviators. Conclusions: Military aviators with MVP may be prone to serious medical complications. A detrimental effect of high-performance flight on patients with MVP is suggested.
Analysis of Sexually Dimorphic Expression of Genes at Early Gonadogenesis of Pejerrey Odontesthes bonariensis Using a Heterologous Microarray
Authors: Fernandino J.I. , Popesku J.T. , Paul-Prasanth B. , Xiong H. , Hattori R.S. , Oura M. , Strüssmann C.A. , Somoza G.M. , Matsuda M. , Nagahama Y. , Trudeau V.L.
Published: March 2011

The process of morphological development of a differentiated gonad from an undifferentiated primordium is a very important step of gonadogenesis. Studies on sexually dimorphic gene expression are important to increase our understanding of this process and to investigate how environmental factors such as temperature can regulate gonadal development. The aim of this study was to identify putative genes involved in sex differentiation in pejerrey (Odontesthes bonariensis) reared at male- and female-producing temperatures (MPT and FPT, respectively) using a microarray heterologous from the medaka (Oryzias latipes), a closely phylogenetic species. Genes related to numerous processes presented higher expression at MPT, including those involved in muscular contraction, metabolic pathways, developmental processes, and reproduction. Genes induced by FPT were classified under the gene ontology terms of response to stimulus, transport and proteolysis. From genes selected for validation, at MPT ndrg3 expression was observed in the somatic cells, whereas pen-2 was detected in germ cells in the caudal portion of the gonads, where no apoptotic signals were observed. Finally, hsp90 was highly expressed in somatic cells of the gonads at the FPT. The results suggest that the interplay of pro-apoptotic and anti-apoptotic genes is important during the masculinization process and for the prevention of sterility following exposure to warm temperatures.
Repetitive Nerve Stimulation of Facial and Hypothenar Muscles: Relative Sensitivity in Different Myasthenia Gravis Subgroups
Authors: Zambelis T. , Kokotis P. , Karandreas N.
Published: March 2011

Aim: To assess the utility of repetitive nerve stimulation (RNS) in facial and hypothenar muscles in the clinical groups of myasthenia gravis (MG). Patients and Methods: We performed RNS study in the orbicularis oculi (O.O.), nasalis and abductor digiti quinti (ADQ) in 115 consecutive myasthenic patients and classified them according to the classifications of the Myasthenia Gravis Foundation of America. Patients were classified into three groups: group 1, group 2 (IIa, IIIa and IVa) and group 3 (IIb, IIIb and IVb). Results: RNS was abnormal in 95 patients (82.6%): 78.3% in the O.O., 66.1% in the nasalis and 19.1% in the ADQ. Both facial muscles were statistically more sensitive than the ADQ in all groups of patients. RNS in the O.O. was more frequently abnormal than in the nasalis only in group 1. Sensitivity to acetylcholine antibodies in myasthenic patients was 84%. Acetylcholine receptor (AChR) and muscle-specific tyrosine kinase antibodies were present in 96.7% of the patients with abnormal RNS in both facial muscles. Single-fiber electromyogram (SFEMG) was abnormal in 91.3% of the tested patients. One of the three tests used for the diagnosis of MG (AChR antibodies, SFEMG, RNS) was abnormal in 99.1% of the patients. Discussion: O.O. is the most sensitive muscle in all groups of MG followed by nasalis, while the ADQ is the muscle with the lowest sensitivity. Facial muscles, especially the O.O., should be the first to be tested in MG. The negativity of all tests (RNS, AChR antibodies, SFEMG) should question the diagnosis of MG, even in the presence of symptoms consistent with MG.
Dynamic Damping Properties of Thermoplastic Elastomers Based on EVA and Recycled Ground Tire Rubber
Authors: Roche N. , Ichchou M.N. , Salvia M. , Chettah A.
Published: March 2011

Recycling waste tires being important for both economical and environmental reasons, ground tire rubber can be blended with other polymers, modifying their properties. In order to characterize and explain these modifications, an experimental study was carried out concerning the improvement in the dynamic damping properties when adding recycled ground tire rubber (GTR) fillers to an elastomeric matrix (ethylene vinyl acetate, EVA).To evaluate the influence of both the GTR and the porosity in a GTR/ EVA composite, three samples have been elaborated by injection:the EVA matrix alone, a GTR/EVA composite, and a GTR/EVA porous composite. Dynamic measurements of the samples were performed using dynamic mechanical thermal analysis. The Young’s modulus and loss factor of these materials are estimated using the frequency—temperature equivalence introduced by Williams—Landel—Ferry expanding the measurement of the dynamic properties over a wider range of frequencies. This method showed that in low-frequency bandwidth, the loss factor has been improved by the addition of GTR to the EVA matrix. The α-relaxation study showed lower activation energy for both the GTR-filled composites leading to the conclusion that the mobility of the polymer chains has been improved by addition of GTR. The impact behavior study carried out using a weight drop test experiment also concluded to better impact energy absorption for the GTR-filled composites at the expense of a larger maximum displacement.
The Distribution of Outcomes Research Papers Across Clinical Journals
Authors: Goldsack Jennifer , McLaughlin Chris , Bristol Mirar N. , Loeb Alex , Bergey Meredith , Sonnad Seema S.
Published: March 2011

This study examines the distribution of health outcomes research (HOR) studies in the clinical literature by clinical areas and journal impact factor. The authors reviewed 535 journals and divided the sample into higher and lower impact journals across four clinical area. Mann-Whitney and Kruskal-Wallis tests were used to examine differences across four categories of outcomes research articles published, specifically the incidence of articles in higher versus lower impact journals and differences across clinical areas. All high-impact journals published more safety and quality articles than process assessment, quality of life, or cost analysis studies. The number of each type of outcomes research study published was highly variable across all clinical areas. Only arthritis and outcomes research journals showed statistically significant differences between higher versus lower impact journals. Authors may benefit from considering these differences in their clinical specialty area when deciding where to submit HOR studies.
The Neighborhood Voice
Authors: Alcaraz Kassandra I. , Weaver Nancy L. , Andresen Elena M. , Christopher Kara , Kreuter Matthew W.
Published: March 2011

The Neighborhood Voice is a vehicle customized for conducting health research in community settings. It brings research studies into neighborhoods affected most by health disparities and reaches groups often underrepresented in research samples. This paper reports on the experience and satisfaction of 599 African American women who participated in research on board the Neighborhood Voice. Using bivariate, psychometric, and logistic regression analyses, we examined responses to a brief post-research survey. Most women (71%) reported that they had never previously participated in research, and two-thirds (68%) rated their Neighborhood Voice experience as excellent. Satisfaction scores were highest among first-time research participants ( p < .05). Women’s ratings of the Neighborhood Voice on Comfort (OR = 4.9; 95% CI = 3.0, 7.9) and Convenience (OR = 1.8; 95% CI = 1.2, 2.9) significantly predicted having an excellent experience. Mobile research facilities may increase participation among disadvantaged and minority populations. Our brief survey instrument is a model for evaluating such outreach.