bluuebunny/crossref_metadata_2025 huggingface dataset:
Sympathetic Skin Responses Evoked by Different Stimuli Modalities in Spinal Cord Injury Patients
Authors: Kumru Hatice , Vidal Joan , Perez Maria , Schestatsky Pedro , Valls-Solé Josep
Published: January 2009

Objective. By using a combination of physiological and electrical peripheral nerve stimuli, the authors aimed to characterize the expected dysfunction of the circuits responsible for sympathetic skin response (SSR) in persons with spinal cord injury (SCI). Methods. The authors examined SSR induced in the hand and foot in 50 SCI patients and 15 age-matched and gender-matched healthy volunteers. SSR was induced by deep inhalation, unexpected acoustic stimuli, brisk hand muscle contraction, and median and peroneal nerve electrical stimulation (PNS). Results. SSRs to any stimulus modality were absent in hand and foot in patients with complete SCI above the T4 level. They were present in the hand and absent in the foot in complete SCI patients at levels between T4 and T11 for all stimuli modalities except PNS. The elicitability of SSR was lower with peroneal nerve stimulation than the other stimuli in hand and foot. The mean latency difference between SSRs of the hand and foot was significantly longer in patients than in controls, regardless of stimulus modality. The amplitude of SSR was larger in volunteers than in patients. Conclusion . SSR to various stimuli confirms the importance of supraspinal centers and the integrity of sympathetic descending pathways. Simultaneous recording of the SSR in the hands and feet provides information about the degree of sympathetic impairment possibly in the efferent pathway. To monitor spontaneous recovery or the efficacy of a drug or biological therapeutic intervention, changes in the latency delay between the hand and foot may be valuable.
Reducing the risk: the use of placebo respiratory equipment in clinical practice
Authors: Richardson M. , Wyllie S. , Dennis A. , Fehrenbach C.
Published: January 2009

Placebo respiratory devices, such as inhalers, large volume spacers and peak flow meters provide reli able methods of teaching patients effective drug able methods of teaching patients effective drug delivery techniques and monitoring compliance and treatment progress. Concern has been raised that using such demonstration devices on more than one person may expose patients to the risk of cross-infection with pathogenic organisms. The lack of regulation and guidance on the use and decontamination of placebo devices prompted us to complete a risk assessment, examining the likelihood and consequence of acquisition of pathogens and resultant illness in our respiratory patient group.
Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation
Authors: Giblin William , Chatterji Monalisa , Westfield Gerwin , Masud Tehmina , Theisen Brian , Cheng Hwei-Ling , DeVido Jeffrey , Alt Frederick W. , Ferguson David O. , Schatz David G. , Sekiguchi JoAnn
Published: January 2009

The RAG1/2 endonuclease initiates programmed DNA rearrangements in progenitor lymphocytes by generating double-strand breaks at specific recombination signal sequences. This process, known as V(D)J recombination, assembles the vastly diverse antigen receptor genes from numerous V, D, and J coding segments. In vitro biochemical and cellular transfection studies suggest that RAG1/2 may also play postcleavage roles by forming complexes with the recombining ends to facilitate DNA end processing and ligation. In the current study, we examine the in vivo consequences of a mutant form of RAG1, RAG1-S723C, that is proficient for DNA cleavage, yet exhibits defects in postcleavage complex formation and end joining in vitro. We generated a knockin mouse model harboring the RAG1-S723C hypomorphic mutation and examined the immune system in this fully in vivo setting. RAG1-S723C homozygous mice exhibit impaired lymphocyte development and decreased V(D)J rearrangements. Distinct from RAG nullizygosity, the RAG1-S723C hypomorph results in aberrant DNA double-strand breaks within rearranging loci. RAG1-S723C also predisposes to thymic lymphomas associated with chromosomal translocations in a p53 mutant background, and heterozygosity for the mutant allele accelerates age-associated immune system dysfunction. Thus, our study provides in vivo evidence that implicates aberrant RAG1/2 activity in lymphoid tumor development and premature immunosenescence.
Upstream sequence elements direct post-transcriptional regulation of gene expression under stress conditions in yeast
Authors: Lawless Craig , Pearson Richard D , Selley Julian N , Smirnova Julia B , Grant Christopher M , Ashe Mark P , Pavitt Graham D , Hubbard Simon J
Published: January 2009

Background

The control of gene expression in eukaryotic cells occurs both transcriptionally and post-transcriptionally. Although many genes are now known to be regulated at the translational level, in general, the mechanisms are poorly understood. We have previously presented polysomal gradient and array-based evidence that translational control is widespread in a significant number of genes when yeast cells are exposed to a range of stresses. Here we have re-examined these gene sets, considering the role of UTR sequences in the translational responses of these genes using recent large-scale datasets which define 5' and 3' transcriptional ends for many yeast genes. In particular, we highlight the potential role of 5' UTRs and upstream open reading frames (uORFs).

Results

We show a highly significant enrichment in specific GO functional classes for genes that are translationally up- and down-regulated under given stresses (e.g. carbohydrate metabolism is up-regulated under amino acid starvation). Cross-referencing these data with the stress response data we show that translationally upregulated genes have longer 5' UTRs, consistent with their role in translational regulation. In the first genome-wide study of uORFs in a set of mapped 5' UTRs, we show that uORFs are rare, being statistically under-represented in UTR sequences. However, they have distinct compositional biases consistent with their putative role in translational control and are more common in genes which are apparently translationally up-regulated.

Conclusion

These results demonstrate a central regulatory role for UTR sequences, and 5' UTRs in particular, highlighting the significant role of uORFs in post-transcriptional control in yeast. Yeast uORFs are more highly conserved than has been suggested, lending further weight to their significance as functional elements involved in gene regulation. It also suggests a more complex and novel mechanism of control, whereby uORFs permit genes to escape from a more general attenuation of translation under conditions of stress. However, since uORFs are relatively rare (only ~13% of yeast genes have them) there remain many unanswered questions as to how UTR elements can direct translational control of many hundreds of genes under stress.
Reporter gene-expressing bone marrow-derived stromal cells are immune-tolerated following implantation in the central nervous system of syngeneic immunocompetent mice
Authors: Bergwerf Irene , De Vocht Nathalie , Tambuyzer Bart , Verschueren Jacob , Reekmans Kristien , Daans Jasmijn , Ibrahimi Abdelilah , Van Tendeloo Viggo , Chatterjee Shyama , Goossens Herman , Jorens Philippe G , Baekelandt Veerle , Ysebaert Dirk , Van Marck Eric , Berneman Zwi N , Linden Annemie Van Der , Ponsaerts Peter
Published: January 2009

Background

Cell transplantation is likely to become an important therapeutic tool for the treatment of various traumatic and ischemic injuries to the central nervous system (CNS). However, in many pre-clinical cell therapy studies, reporter gene-assisted imaging of cellular implants in the CNS and potential reporter gene and/or cell-based immunogenicity, still remain challenging research topics.

Results

In this study, we performed cell implantation experiments in the CNS of immunocompetent mice using autologous (syngeneic) luciferase-expressing bone marrow-derived stromal cells (BMSC-Luc) cultured from ROSA26-L-S-L-Luciferase transgenic mice, and BMSC-Luc genetically modified using a lentivirus encoding the enhanced green fluorescence protein (eGFP) and the puromycin resistance gene (Pac) (BMSC-Luc/eGFP/Pac). Both reporter gene-modified BMSC populations displayed high engraftment capacity in the CNS of immunocompetent mice, despite potential immunogenicity of introduced reporter proteins, as demonstrated by real-time bioluminescence imaging (BLI) and histological analysis at different time-points post-implantation. In contrast, both BMSC-Luc and BMSC-Luc/eGFP/Pac did not survive upon intramuscular cell implantation, as demonstrated by real-time BLI at different time-points post-implantation. In addition, ELISPOT analysis demonstrated the induction of IFN-γ-producing CD8+ T-cells upon intramuscular cell implantation, but not upon intracerebral cell implantation, indicating that BMSC-Luc and BMSC-Luc/eGFP/Pac are immune-tolerated in the CNS. However, in our experimental transplantation model, results also indicated that reporter gene-specific immune-reactive T-cell responses were not the main contributors to the immunological rejection of BMSC-Luc or BMSC-Luc/eGFP/Pac upon intramuscular cell implantation.

Conclusion

We here demonstrate that reporter gene-modified BMSC derived from ROSA26-L-S-L-Luciferase transgenic mice are immune-tolerated upon implantation in the CNS of syngeneic immunocompetent mice, providing a research model for studying survival and localisation of autologous BMSC implants in the CNS by real-time BLI and/or histological analysis in the absence of immunosuppressive therapy.
Catalytic inhibition of topoisomerase II by a novel rationally designed ATP-competitive purine analogue
Authors: Chène Patrick , Rudloff Joëlle , Schoepfer Joseph , Furet Pascal , Meier Peter , Qian Zhiyan , Schlaeppi Jean-Marc , Schmitz Rita , Radimerski Thomas
Published: January 2009

Background

Topoisomerase II poisons are in clinical use as anti-cancer therapy for decades and work by stabilizing the enzyme-induced DNA breaks. In contrast, catalytic inhibitors block the enzyme before DNA scission. Although several catalytic inhibitors of topoisomerase II have been described, preclinical concepts for exploiting their anti-proliferative activity based on molecular characteristics of the tumor cell have only recently started to emerge. Topoisomerase II is an ATPase and uses the energy derived from ATP hydrolysis to orchestrate the movement of the DNA double strands along the enzyme. Thus, interfering with ATPase function with low molecular weight inhibitors that target the nucleotide binding pocket should profoundly affect cells that are committed to undergo mitosis.

Results

Here we describe the discovery and characterization of a novel purine diamine analogue as a potent ATP-competitive catalytic inhibitor of topoisomerase II. Quinoline aminopurine compound 1 (QAP 1) inhibited topoisomerase II ATPase activity and decatenation reaction at sub-micromolar concentrations, targeted both topoisomerase II alpha and beta in cell free assays and, using a quantitative cell-based assay and a chromosome segregation assay, displayed catalytic enzyme inhibition in cells. In agreement with recent hypothesis, we show that BRCA1 mutant breast cancer cells have increased sensitivity to QAP 1.

Conclusion

The results obtained with QAP 1 demonstrate that potent and selective catalytic inhibition of human topoisomerase II function with an ATP-competitive inhibitor is feasible. Our data suggest that further drug discovery efforts on ATP-competitive catalytic inhibitors are warranted and that such drugs could potentially be developed as anti-cancer therapy for tumors that bear the appropriate combination of molecular alterations.
Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy
Authors: Zabala Maider , Alzuguren Pilar , Benavides Carolina , Crettaz Julien , Gonzalez-Aseguinolaza Gloria , Ortiz de Solorzano Carlos , Gonzalez-Aparicio Manuela , Kramer Maria Gabriela , Prieto Jesus , Hernandez-Alcoceba Ruben
Published: January 2009

Background

Bioluminescent imaging (BLI) is based on the detection of light emitted by living cells expressing a luciferase gene. Stable transfection of luciferase in cancer cells and their inoculation into permissive animals allows the noninvasive monitorization of tumor progression inside internal organs. We have applied this technology for the development of a murine model of colorectal cancer involving the liver, with the aim of improving the pre-clinical evaluation of new anticancer therapies.

Results

A murine colon cancer cell line stably transfected with the luciferase gene (MC38Luc1) retains tumorigenicity in immunocompetent C57BL/6 animals. Intrahepatic inoculation of MC38Luc1 causes progressive liver infiltration that can be monitored by BLI. Compared with ultrasonography (US), BLI is more sensitive, but accurate estimation of tumor mass is impaired in advanced stages. We applied BLI to evaluate the efficacy of an immunogene therapy approach based on the liver-specific expression of the proinflammatory cytokine interleukin-12 (IL-12). Individualized quantification of light emission was able to determine the extent and duration of antitumor responses and to predict long-term disease-free survival.

Conclusion

We show that BLI is a rapid, convenient and safe technique for the individual monitorization of tumor progression in the liver. Evaluation of experimental treatments with complex mechanisms of action such as immunotherapy is possible using this technology.
Integrated taxonomy: traditional approach and DNA barcoding for the identification of filarioid worms and related parasites (Nematoda)
Authors: Ferri Emanuele , Barbuto Michela , Bain Odile , Galimberti Andrea , Uni Shigehiko , Guerrero Ricardo , Ferté Hubert , Bandi Claudio , Martin Coralie , Casiraghi Maurizio
Published: January 2009

Background

We compared here the suitability and efficacy of traditional morphological approach and DNA barcoding to distinguish filarioid nematodes species (Nematoda, Spirurida). A reliable and rapid taxonomic identification of these parasites is the basis for a correct diagnosis of important and widespread parasitic diseases. The performance of DNA barcoding with different parameters was compared measuring the strength of correlation between morphological and molecular identification approaches. Molecular distance estimation was performed with two different mitochondrial markers (coxIand 12S rDNA) and different combinations of data handling were compared in order to provide a stronger tool for easy identification of filarioid worms.

Results

DNA barcoding and morphology based identification of filarioid nematodes revealed high coherence. Despite bothcoxIand 12S rDNA allow to reach high-quality performances, onlycoxIrevealed to be manageable. Both alignment algorithm, gaps treatment, and the criteria used to define the threshold value were found to affect the performance of DNA barcoding with 12S rDNA marker. UsingcoxIand a defined level of nucleotide divergence to delimit species boundaries, DNA barcoding can also be used to infer potential new species.

Conclusion

An integrated approach allows to reach a higher discrimination power. The results clearly show where DNA-based and morphological identifications are consistent, and where they are not. The coherence between DNA-based and morphological identification for almost all the species examined in our work is very strong. We propose DNA barcoding as a reliable, consistent, and democratic tool for species discrimination in routine identification of parasitic nematodes.
An HPV 16 L1-based chimeric human papilloma virus-like particles containing a string of epitopes produced in plants is able to elicit humoral and cytotoxic T-cell activity in mice
Authors: Paz de la Rosa Georgina , Monroy-García Alberto , Mora-García María de Lourdes , Peña Cristina Gehibie Reynaga , Hernández-Montes Jorge , Weiss-Steider Benny , Gómez Lim Miguel Angel
Published: January 2009

Background

Even though two prophylactic vaccines against HPV are currently licensed, infections by the virus continue to be a major health problem mainly in developing countries. The cost of the vaccines limits wide-scale application in poor countries. A promising strategy for producing affordable and efficient vaccines involves the expression of recombinant immunogens in plants. Several HPV genes have been expressed in plants, including L1, which can self-assemble into virus-like particles. A plant-based, dual prophylactic/therapeutic vaccine remains an attractive possibility.

Results

We sought to express in tomato plants chimeric HPV 16 VLPs containing L1 fused to a string of epitopes from HPV 16 E6 and E7 proteins. The L1 employed had been modified to eliminate a strong inhibitory region at the 5' end of the molecule to increase expression levels. Several tomato lines were obtained expressing either L1 alone or L1-E6/E7 from 0.05% to 0.1% of total soluble protein. Stable integration of the transgenes was verified by Southern blot. Northern and western blot revealed successful expression of the transgenes at the mRNA and protein level. The chimeric VLPs were able to assemble adequately in tomato cells. Intraperitoneal administration in mice was able to elicit both neutralizing antibodies against the viral particle and cytotoxic T-lymphocytes activity against the epitopes.

Conclusion

In this work, we report for the first time the expression in plants of a chimeric particle containing the HPV 16 L1 sequence and a string of T-cell epitopes from HPV 16 E6 and E7 fused to the C-terminus. The particles were able to induce a significant antibody and cytotoxic T-lymphocytes response. Experimentsin vivoare in progress to determine whether the chimeric particles are able to induce regression of disease and resolution of viral infection in mice. Chimeric particles of the type described in this work may potentially be the basis for developing prophylactic/therapeutic vaccines. The fact that they are produced in plants, may lower production costs considerably.
Osseointegration of zirconia implants compared with titanium: an in vivo study
Authors: Depprich Rita , Zipprich Holger , Ommerborn Michelle , Naujoks Christian , Wiesmann Hans-Peter , Kiattavorncharoen Sirichai , Lauer Hans-Christoph , Meyer Ulrich , Kübler Norbert R , Handschel Jörg
Published: January 2009

Background

Titanium and titanium alloys are widely used for fabrication of dental implants. Since the material composition and the surface topography of a biomaterial play a fundamental role in osseointegration, various chemical and physical surface modifications have been developed to improve osseous healing. Zirconia-based implants were introduced into dental implantology as an altenative to titanium implants. Zirconia seems to be a suitable implant material because of its tooth-like colour, its mechanical properties and its biocompatibility. As the osseointegration of zirconia implants has not been extensively investigated, the aim of this study was to compare the osseous healing of zirconia implants with titanium implants which have a roughened surface but otherwise similar implant geometries.

Methods

Forty-eight zirconia and titanium implants were introduced into the tibia of 12 minipigs. After 1, 4 or 12 weeks, animals were sacrificed and specimens containing the implants were examined in terms of histological and ultrastructural techniques.

Results

Histological results showed direct bone contact on the zirconia and titanium surfaces. Bone implant contact as measured by histomorphometry was slightly better on titanium than on zirconia surfaces. However, a statistically significant difference between the two groups was not observed.

Conclusion

The results demonstrated that zirconia implants with modified surfaces result in an osseointegration which is comparable with that of titanium implants.
Characterization of a prenatally assessed de novo supernumerary minute ring chromosome 20 in a phenotypically normal male
Authors: Kitsiou-Tzeli Sofia , Manolakos Emmanouil , Lagou Magdalini , Kontodiou Maria , Kosyakova Nadezda , Ewers Elisabeth , Weise Anja , Garas Antonios , Orru Sandro , Liehr Thomas , Metaxotou Aikaterini
Published: January 2009

Background

The heterogeneous group of small supernumerary marker chromosomes (sSMCs) presents serious counseling problems, especially if they are present de novo and diagnosed prenatally. The incidence has been estimated at 1 in 1000 prenatal samples. We present a case of mosaic sSMC diagnosed prenatally after amniocentesis. The sSMC was characterized by various molecular cytogenetic techniques and determined to be a r(20) chromosome. After genetic counseling, the parents decided to continue the pregnancy, and a boy with minor phenotypic variants was born after 39 weeks of pregnancy. The case is compared with four other cases of prenatally detected r(20) mosaicism.

Results

Here we describe a 3 months old male child with normal pre- and postnatal development and with a de novo ring supernumerary marker chromosome in amniocytes cultures. Using new fluorescence in situ hybridization (FISH) techniques, three distinguishable sSMCs (cryptic mosaicism), all derived from chromosome 20, were observed, including ring and minute chromosomes. This heterogeneity was impossible to detect by the conventional G-banding technique or conventional FISH technique that were used before the application of new FISH techniques (subcentromere-specific multicolor-FISH [subcenM-FISH]) and a probe, specific for the 20p12.2 band. The sSMC present in 25% of the cells was present as r(20)(::p12.2~12.3->q11.1::)[5]/r(20;20)(::p12.1->q11.1::q11.1 >p12.1::)[2]/min(20;20)(:p12.1->q11.1::q11.1->p12.1:)[1]. The final karyotype was 47,XY,+r(20)[25%]/46,XY[75%].

Conclusion

We emphasize the importance of application of molecular cytogenetics in a prenatally diagnostic laboratory and description of more cases to enable a better genetic counseling and risk evaluation.
Identification of a rare de novo three-way complex t(5;20;8)(q31;p11.2;p21) with microdeletions on 5q31.2, 5q31.3, and 8p23.2 in a patient with hearing loss and global developmental delay: case report
Authors: Haj Roland , Jackson Kelly , Torchia Beth A , Shaffer Lisa G , Bejjani Bassem A , Gowans Gordon C , Ruff Michael E
Published: January 2009

Background

Complex chromosome rearrangements (CCRs), which involve more than two breakpoints on two or more chromosomes, are uncommon occurrences. Although most CCRs appear balanced at the level of the light microscope, many demonstrate cryptic, submicroscopic imbalances at the translocation breakpoints.

Results

We report a female with hearing loss and global developmental delay with a complex three-way unbalanced translocation (5;20;8)(q31;p11.2;p21) resulting in microdeletions on 5q31.2, 5q31.3, and 8p23.2 identified by karyotyping, microarray analysis and fluorescence in situ hybridization.

Discussion

The microdeletion of bands 8p23.2 may be associated with the hearing impairment. Furthermore, the characterization of this patient's chromosomal abnormalities demonstrates the importance of integrated technologies within contemporary cytogenetics laboratories.
Giant lymphatic cyst of omentum: a case report
Authors: Kumar Sanjeev , Agrawal Nikhil , Khanna Rahul , Khanna AK
Published: January 2009

Background

Omental cysts are rare abdominal lesions and are difficult to diagnose. Mostly they are detected incidentally during imaging studies performed for unrelated reasons.

Case presentation

Presentation can be both acute and chronic. Acute presentations are usually due to complication in cyst. Imaging is helpful in excluding other causes of lump abdomen.

We encountered a case of giant lymphatic cyst presenting with abdominal swelling, clinically mimicking huge ovarian cyst.

Conclusion

The goal of surgical therapy is complete excision of the cyst, and Omental cysts can be removed without endangering the adjacent bowel.
MRI bone oedema scores are higher in the arthritis mutilans form of psoriatic arthritis and correlate with high radiographic scores for joint damage
Authors: Tan Yu M , Østergaard Mikkel , Doyle Anthony , Dalbeth Nicola , Lobo Maria , Reeves Quentin , Robinson Elizabeth , Taylor William J , Jones Peter B , Pui Karen , Lee Jamie , McQueen Fiona M
Published: January 2009

Introduction

The aim of this study was to investigate the magnetic resonance imaging (MRI) features of bone disease in the arthritis mutilans (AM) form of psoriatic arthritis (PsA).

Methods

Twenty-eight patients with erosive PsA were enrolled (median disease duration of 14 years). Using x-rays of both hands and feet, 11 patients were classified as AM and 17 as non-AM (erosive psoriatic arthritis without bone lysis)by two observers. MRI scans (1.5T) of the dominant hand (wrist and fingers scanned separately) were obtained using standard contrast-enhanced T1-weighted and fat-saturated T2-weighted sequences. Scans were scored separately by two readers for bone erosion, oedema and proliferation using a PsA MRI scoring system. X-rays were scored for erosions and joint space narrowing.

Results

On MRI, 1013 bones were scored by both readers. Reliability for scoring erosions and bone oedema was high (intraclass correlation coefficients = 0.80 and 0.77 respectively) but only fair for bone proliferation (intraclass correlation coefficient = 0.42). MRI erosion scores were higher in AM patients (53.0 versus 15.0, p = 0.004) as were bone oedema and proliferation scores (14.7 versus 10.0, p = 0.056 and 3.6 versus 0.7, p = 0.003 respectively). MRI bone oedema scores correlated with MRI erosion scores and X-ray erosion and joint space narrowing scores (r = 0.65, p = 0.0002 for all) but not the disease activity score 28-C reactive protein (DAS28CRP) or pain scores.

Conclusions

In this patient group with PsA, MRI bone oedema, erosion and proliferation were all more severe in the AM-form. Bone oedema scores did not correlate with disease activity measures but were closely associated with X-ray joint damage scores. These results suggest that MRI bone oedema may be a pre-erosive feature and that bone damage may not be coupled with joint inflammation in PsA.
Prevelar Raising and Phonetic Conditioning: Role of Labial and Anterior Tongue Gestures
Authors: Purnell Thomas C.
Published: January 2009

This article analyzes prevelar raising of /æ/, a restructuring present in the Upper Midwestern United States, from an articulatory perspective. Labov, Ash, and Boberg raise the question as to where this phenomenon lies within the range of uniform gestures. The present article describes lingual, mandibular, and labial movements in producing raised and unraised /æ/ in order to answer the question as to why /æg/ is elevated in the vowel space above /æk/ even when speakers are not participating in the prevelar raising. Results of a study of speakers who raise /æ/ before /g/ compared to a cohort of nonraisers reveal that in addition to a more anterior gesture for /æ/ before /g/ than before /k/, there is statistically significant lip repositioning associated with the raising gesture. The results highlight limitations of sound change descriptions when only acoustic data is available.
/æ/-RAISING in Wisconsin English
Authors: Bauer Matt , Parker Frank
Published: January 2009

The raising of /æ/ before voiced velars (such that bag is perceived as beg) has been noted and documented sporadically in the American Midwest over the past 60 years. Commentaries range from the impressionistic to the acoustically based. Here we present not only acoustic but also articulatory data from ultrasound gathered from speakers of the dialect in question. Our results from a speech production experiment show that /æ/ is in fact raised before /g/ in the affected dialect, but not so much that it merges with either /e/ or /ϵ/. Instead, this raising appears to follow from coarticulatory effects and is consistent with a perception-based theory that sound change results when listeners fail to correct for such effects and end up internalizing a novel target. Moreover, the proximity of /eg/ to raised /æg/ appears to have led speakers of this dialect to reanalyze the few /eg/ words in the lexicon (e.g., vague, plague, and bagel) as containing /æg/.
Decentralized search on spheres using small-world Markov chains: expected hitting times and structural properties
Authors: Ghate Archis
Published: January 2009

We build a family of Markov chains on a sphere using distance-based long-range connection probabilities to model the decentralized message-passing problem that has recently gained significant attention in the small-world literature. Starting at an arbitrary source point on the sphere, the expected message delivery time to an arbitrary target on the sphere is characterized by a particular expected hitting time of our Markov chains. We prove that, within this family, there is a unique efficient Markov chain whose expected hitting time is polylogarithmic in the relative size of the sphere. For all other chains, this expected hitting time is at least polynomial. We conclude by defining two structural properties, called scale invariance and steady improvement, of the probability density function of long-range connections and prove that they are sufficient and necessary for efficient decentralized message delivery.
Uniform approximations of discrete-time filters
Authors: Heine Kari , Crisan Dan
Published: January 2009

Throughout recent years, various sequential Monte Carlo methods, i.e. particle filters, have been widely applied to various applications involving the evaluation of the generally intractable stochastic discrete-time filter. Although convergence results exist for finite-time intervals, a stronger form of convergence, namely, uniform convergence, is required for bounding the error on an infinite-time interval. In this paper we prove easily verifiable conditions for the filter applications that are sufficient for the uniform convergence of certain particle filters. Essentially, the conditions require the observations to be accurate enough. No mixing or ergodicity conditions are imposed on the signal process.
Expected coalescence time for a nonuniform allocation process
Authors: McSweeney John K. , Pittel Boris G.
Published: January 2009

We study a process where balls are repeatedly thrown intonboxes independently according to some probability distributionp. We start withnballs, and at each step, all balls landing in the same box are fused into a single ball; the process terminates when there is only one ball left (coalescence). Letc:= ∑jpj2, the collision probability of two fixed balls. We show that the expected coalescence time is asymptotically 2c−1, under two constraints onpthat exclude a thin set of distributionsp. One of the constraints isc=o(ln−2n). This ln−2nis shown to be a threshold value: forc= ω(ln−2n), there existspwithc(p) =csuch that the expected coalescence time far exceedsc−1. Connections to coalescent processes in population biology and theoretical computer science are discussed.
Exact values and sharp estimates for the total variation distance between binomial and Poisson distributions
Authors: Adell José A. , Anoz José M. , Lekuona Alberto
Published: January 2009

We present a method to obtain both exact values and sharp estimates for the total variation distance between binomial and Poisson distributions with the same mean λ. We give a simple efficient algorithm, whose complexity order isto compute exact values. Such an algorithm can be further simplified for moderate sample sizesn, provided that λ is neither close tofrom the left nor close tofrom the right. Sharp estimates, better than other known estimates in the literature, are also provided. The 0s of the second Krawtchouk and Charlier polynomials play a fundamental role.
Large deviations for eigenvalues of sample covariance matrices, with applications to mobile communication systems
Authors: Fey Anne , van der Hofstad Remco , Klok Marten J.
Published: January 2009

We study sample covariance matrices of the form W = (1 / n)CCT, where C is a k x n matrix with independent and identically distributed (i.i.d.) mean 0 entries. This is a generalization of the so-called Wishart matrices, where the entries of C are i.i.d. standard normal random variables. Such matrices arise in statistics as sample covariance matrices, and the high-dimensional case, when k is large, arises in the analysis of DNA experiments. We investigate the large deviation properties of the largest and smallest eigenvalues of W when either k is fixed and n → ∞ or kn → ∞ with kn = o(n / log log n), in the case where the squares of the i.i.d. entries have finite exponential moments. Previous results, proving almost sure limits of the eigenvalues, require only finite fourth moments. Our most explicit results for large k are for the case where the entries of C are ∓ 1 with equal probability. We relate the large deviation rate functions of the smallest and largest eigenvalues to the rate functions for i.i.d. standard normal entries of C. This case is of particular interest since it is related to the problem of decoding of a signal in a code-division multiple-access (CDMA) system arising in mobile communication systems. In this example, k is the number of users in the system and n is the length of the coding sequence of each of the users. Each user transmits at the same time and uses the same frequency; the codes are used to distinguish the signals of the separate users. The results imply large deviation bounds for the probability of a bit error due to the interference of the various users.
Analysis of stochastic fluid queues driven by local-time processes
Authors: Konstantopoulos Takis , Kyprianou Andreas E. , Salminen Paavo , Sirviö Marina
Published: January 2009

We consider a stochastic fluid queue served by a constant rate server and driven by a process which is the local time of a reflected Lévy process. Such a stochastic system can be used as a model in a priority service system, especially when the time scales involved are fast. The input (local time) in our model is typically (but not necessarily) singular with respect to the Lebesgue measure, a situation which, in view of the nonsmooth or bursty nature of several types of Internet traffic, is nowadays quite realistic. We first discuss how to rigorously construct the (necessarily) unique stationary version of the system under some natural stability conditions. We then consider the distribution of performance steady-state characteristics, namely, the buffer content, the idle period, and the busy period. These derivations are much based on the fact that the inverse of the local time of a Markov process is a Lévy process (a subordinator), hence making the theory of Lévy processes applicable. Another important ingredient in our approach is the use of Palm calculus for stationary random point processes and measures.
State-dependent importance sampling for regularly varying random walks
Authors: Blanchet Jose H. , Liu Jingchen
Published: January 2009

Consider a sequence (Xk:k≥ 0) of regularly varying independent and identically distributed random variables with mean 0 and finite variance. We develop efficient rare-event simulation methodology associated with large deviation probabilities for the random walk (Sn:n≥ 0). Our techniques are illustrated by examples, including large deviations for the empirical mean and path-dependent events. In particular, we describe two efficient state-dependent importance sampling algorithms for estimating the tail ofSnin a large deviation regime asn↗ ∞. The first algorithm takes advantage of large deviation approximations that are used to mimic the zero-variance change of measure. The second algorithm uses a parametric family of changes of measure based on mixtures. Lyapunov-type inequalities are used to appropriately select the mixture parameters in order to guarantee bounded relative error (or efficiency) of the estimator. The second example involves a path-dependent event related to a so-called knock-in financial option under heavy-tailed log returns. Again, the importance sampling algorithm is based on a parametric family of mixtures which is selected using Lyapunov bounds. In addition to the theoretical analysis of the algorithms, numerical experiments are provided in order to test their empirical performance.
Multifractality of products of geometric Ornstein-Uhlenbeck-type processes
Authors: Anh V. V. , Leonenko Nikolai N. , Shieh Narn-Rueih
Published: January 2009

We investigate the properties of multifractal products of geometric Ornstein-Uhlenbeck (OU) processes driven by Lévy motion. The conditions on the mean, variance, and covariance functions of the resulting cumulative processes are interpreted in terms of the moment generating functions. We consider five cases of infinitely divisible distributions for the background driving Lévy processes, namely, the gamma and variance gamma distributions, the inverse Gaussian and normal inverse Gaussian distributions, and thez-distributions. We establish the corresponding scenarios for the limiting processes, including their Rényi functions and dependence structure.
Stochastic and substochastic solutions for infinite-state Markov chains with applications to matrix-analytic methods
Authors: Grassmann Winfried K. , Tavakoli Javad
Published: January 2009

This paper deals with censoring of infinite-state banded Markov chains. Censoring involves reducing the time spent in states outside a certain set of states to 0 without affecting the number of visits within this set. We show that, if all states are transient, there is, besides the standard censored Markov chain, a nonstandard censored Markov chain which is stochastic. Both the stochastic and the substochastic solutions are found by censoring a sequence of finite transition matrices. If all matrices in the sequence are stochastic, the stochastic solution arises in the limit, whereas the substochastic solution arises if the matrices in the sequence are substochastic. We also show that, if the Markov chain is recurrent, the only solution is the stochastic solution. Censoring is particularly fruitful when applied to quasi-birth-and-death (QBD) processes. It turns out that key matrices in such processes are not unique, a fact that has been observed by several authors. We note that the stochastic solution is important for the analysis of finite queues.
A quadratic ARCH(∞) model with long memory and Lévy stable behavior of squares
Authors: Surgailis Donatas
Published: January 2009

We introduce a modification of the linear ARCH (LARCH) model (Giraitis, Robinson, and Surgailis (2000)) - a special case of Sentana's (1995) quadratic ARCH (QARCH) model - for which the conditional variance is a sum of a positive constant and the square of an inhomogeneous linear combination of past observations. Necessary and sufficient conditions for the existence of a stationary solution with finite variance are obtained. We give conditions under which the stationary solution with infinite fourth moment can exhibit long memory, the leverage effect, and a Lévy-stable limit behavior of partial sums of squares.
Entry and Exit Decision Problem with Implementation Delay
Authors: Costeniuc Marius , Schnetzer Michaela , Taschini Luca
Published: January 2009

We study investment and disinvestment decisions in situations where there is a time lagd> 0 from the timetwhen the decision is taken to the timet+dwhen the decision is implemented. In this paper we apply the probabilistic approach to the combined entry and exit decisions under the Parisian implementation delay. In particular, we prove the independence between Parisian stopping times and a general Brownian motion with drift stopped at the stopping time. Relying on this result, we solve the constrained maximization problem, obtaining an analytic solution to the optimal ‘starting’ and ‘stopping’ levels. We compare our results with the instantaneous entry and exit situation, and show that an increase in the uncertainty of the underlying process hastens the decision to invest or disinvest, extending a result of Bar-Ilan and Strange (1996).
A Fourth Moment Inequality for Functionals of Stationary Processes
Authors: Durieu Olivier
Published: January 2009

In this paper, a fourth moment bound for partial sums of functionals of strongly ergodic Markov chains is established. This type of inequality plays an important role in the study of the empirical process invariance principle. This inequality is specially adapted to the technique of Dehling, Durieu, and Volný (2008). The same moment bound can be proved for dynamical systems whose transfer operator has some spectral properties. Examples of applications are given.
Total Time on Test Transforms of Order n and Their Implications in Reliability Analysis
Authors: Nair N. Unnikrishnan , Sankaran P. G. , Kumar B. Vinesh
Published: January 2009

In this paper we study the properties of total time on test transforms of order n and examine their applications in reliability analysis. It is shown that the successive transforms produce either distributions with increasing or bathtub-shaped failure rates or distributions with decreasing or upside bathtub-shaped failure rates. The ageing properties of the baseline distribution is compared with those of transformed distributions, and a partial order based on nth-order transforms and their implications are discussed.
Tails of Stopped Random Products: The Factoid and Some Relatives
Authors: Pakes Anthony G.
Published: January 2009

The upper tail behaviour is explored for a stopped random product ∏j=1NXj, where the factors are positive and independent and identically distributed, and N is the first time one of the factors occupies a subset of the positive reals. This structure is motivated by a heavy-tailed analogue of the factorial n!, called the factoid of n. Properties of the factoid suggested by computer explorations are shown to be valid. Two topics about the determination of the Zipf exponent in the rank-size law for city sizes are discussed.
On Asymptotics of Exchangeable Coalescents with Multiple Collisions
Authors: Gnedin Alexander , Iksanov Alex , Möhle Martin
Published: January 2009

We study the number of collisions, Xn, of an exchangeable coalescent with multiple collisions (Λ-coalescent) which starts with n particles and is driven by rates determined by a finite characteristic measure η(dx) = x−2Λ(dx). Via a coupling technique, we derive limiting laws of Xn, using previous results on regenerative compositions derived from stick-breaking partitions of the unit interval. The possible limiting laws of Xn include normal, stable with index 1 ≤ α < 2, and Mittag-Leffler distributions. The results apply, in particular, to the case when η is a beta(a − 2, b) distribution with parameters a > 2 and b > 0. The approach taken allows us to derive asymptotics of three other functionals of the coalescent: the absorption time, the length of an external branch chosen at random from the n external branches, and the number of collision events that occur before the randomly selected external branch coalesces with one of its neighbours.
Chaoticity for Multiclass Systems and Exchangeability Within Classes
Authors: Graham Carl
Published: January 2009

Classical results for exchangeable systems of random variables are extended to multiclass systems satisfying a natural partial exchangeability assumption. It is proved that the conditional law of a finite multiclass system, given the value of the vector of the empirical measures of its classes, corresponds to independent uniform orderings of the samples within {each} class, and that a family of such systems converges in law {if and only if} the corresponding empirical measure vectors converge in law. As a corollary, convergence within {each} class to an infinite independent and identically distributed system implies asymptotic independence between {different} classes. A result implying the Hewitt-Savage 0-1 law is also extended.
Disease modeling for Ebola and Marburg viruses
Authors: Bente Dennis , Gren Jason , Strong James E. , Feldmann Heinz
Published: January 2009

The filoviruses Ebola and Marburg are zoonotic agents that are classified as both biosafety level 4 and category A list pathogens. These viruses are pathogenic in humans and cause isolated infections or epidemics of viral hemorrhagic fever, mainly in Central Africa. Their natural reservoir has not been definitely identified, but certain species of African bat have been associated with Ebola and Marburg infections. Currently, there are no licensed options available for either treatment or prophylaxis. Different animal models have been developed for filoviruses including mouse, guinea pig and nonhuman primates. The ‘gold standard’ animal models for pathogenesis, treatment and vaccine studies are rhesus and cynomolgus macaques. This article provides a brief overview of the clinical picture and the pathology/pathogenesis of human filovirus infections. The current animal model options are discussed and compared with regard to their value in different applications. In general, the small animal models, in particular the mouse, are the most feasible for high biocontainment facilities and they offer the most options for research owing to the greater availability of immunologic and genetic tools. However, their mimicry of the human diseases as well as their predictive value for therapeutic efficacy in primates is limited, thereby making them, at best, valuable initial screening tools for pathophysiology, treatment and vaccine studies.
Progenitor cell therapies for traumatic brain injury: barriers and opportunities in translation
Authors: Walker Peter A. , Shah Shinil K. , Harting Matthew T. , Cox Charles S.
Published: January 2009

Traumatic brain injury (TBI) directly affects nearly 1.5 million new patients per year in the USA, adding to the almost 6 million cases in patients who are permanently affected by the irreversible physical, cognitive and psychosocial deficits from a prior injury. Adult stem cell therapy has shown preliminary promise as an option for treatment, much of which is limited currently to supportive care. Preclinical research focused on cell therapy has grown significantly over the last decade. One of the challenges in the translation of this burgeoning field is interpretation of the promising experimental results obtained from a variety of cell types, injury models and techniques. Although these variables can become barriers to a collective understanding and to evidence-based translation, they provide crucial information that, when correctly placed, offers the opportunity for discovery. Here, we review the preclinical evidence that is currently guiding the translation of adult stem cell therapy for TBI.