bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial [NCT00256139]
Authors: Ortonne Jean-Paul , Shear Neil , Shumack Stephen , Henninger Eric ,   the CLEAR Multinational Study Group
Published: December 2005

Background

Chronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL) is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG1monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication.

Methods

A total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529) or placebo (n = 264) for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo). The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36) and Dermatology Life Quality Index (DLQI). Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA), a visual analog scale (VAS) for itching, and the Patient's Global Psoriasis Assessment (PGPA).

Results

Efalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P< .001). Corresponding improvements in DLQI in the High-Need cohort were 5.4 points for efalizumab compared to 2.3 for placebo (P< .001). Improvements from baseline on the SF-36, PSA, PGPA, and itching VAS at Week 12 were also significantly greater in efalizumab-treated patients than for placebo.

Conclusion

A 12-week course of efalizumab improved HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis. The benefits of efalizumab therapy in High-Need patients were similar to those observed in the total study population, indicating that the beneficial impact of efalizumab on QOL is consistent regardless of disease severity, prior therapy, or contraindications to previous therapies.
X-ray structure of engineered human Aortic Preferentially Expressed Protein-1 (APEG-1)
Authors: Manjasetty Babu A , Niesen Frank H , Scheich Christoph , Roske Yvette , Goetz Frank , Behlke Joachim , Sievert Volker , Heinemann Udo , Büssow Konrad
Published: December 2005

Background

Human Aortic Preferentially Expressed Protein-1 (APEG-1) is a novel specific smooth muscle differentiation marker thought to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs).

Results

Good quality crystals that were suitable for X-ray crystallographic studies were obtained following the truncation of the 14 N-terminal amino acids of APEG-1, a region predicted to be disordered. The truncated protein (termed ΔAPEG-1) consists of a single immunoglobulin (Ig) like domain which includes an Arg-Gly-Asp (RGD) adhesion recognition motif. The RGD motif is crucial for the interaction of extracellular proteins and plays a role in cell adhesion. The X-ray structure of ΔAPEG-1 was determined and was refined to sub-atomic resolution (0.96 Å). This is the best resolution for an immunoglobulin domain structure so far. The structure adopts a Greek-key β-sandwich fold and belongs to the I (intermediate) set of the immunoglobulin superfamily. The residues lying between the β-sheets form a hydrophobic core. The RGD motif folds into a 310 helix that is involved in the formation of a homodimer in the crystal which is mainly stabilized by salt bridges. Analytical ultracentrifugation studies revealed a moderate dissociation constant of 20 μM at physiological ionic strength, suggesting that APEG-1 dimerisation is only transient in the cell. The binding constant is strongly dependent on ionic strength.

Conclusion

Our data suggests that the RGD motif might play a role not only in the adhesion of extracellular proteins but also in intracellular protein-protein interactions. However, it remains to be established whether the rather weak dimerisation of APEG-1 involving this motif is physiogically relevant.
Encapsulated Escherichia coli in alginate beads capable of secreting a heterologous pectin lyase
Authors: Papi Rigini M , Chaitidou Sotiria A , Trikka Fotini A , Kyriakidis Dimitrios A
Published: December 2005

Background

Production of heterologous proteins in the E. coli periplasm, or into the extracellular fluid has many advantages; therefore naturally occurring signal peptides are selected for proteins translocation. The aim of this study was the production in high yields of a recombinant pectin lyase that is efficiently secreted and the encapsulation of transformed E. coli cells for pectin degradation in a biotechnological process.

Results

The nucleotide sequence of Bacillus subtilis α-amylase's signal peptide was fused to the N-terminal of an heterologously expressed pectin lyase in E. coli BL21 [DE3]. Thus pectin lyase secretion was achieved into the extracellular growth medium. E. coli cells harboring the recombinant plasmid heterologously express pectin lyase to around 22% of the total cellular proteins, as it was estimated by SDS-PAGE and image analysis. IPTG induces the heterologously expressed enzyme, which is initially distributed extracellularly (7 hour) and later on at the periplasmic (9 hours) or cytosolic fraction (20 hours). No pectin lyase activity was found in the membranes fraction and in the inclusion bodies. Encapsulation of the recombinant strains of E. coli in alginate or alginate/silica beads 1:5 showed that pectin lyase could degrade effectively its substrate, for at least ten operational cycles.

Conclusion

Secretion of an heterologously overexpressed pectin lyase in E. coli BL21 [DE3] was achieved in this study. For this purpose the signal peptide of α-amylase from B. subtilis was fused to the N-terminal domain of pectin lyase. Encapsulated E. coli BL21 [DE3] cells harboring pET29c/exPNL were used successfully for pectin degradation up to ten operational cycles indicating that under special conditions this might have biotechnological implementations.
Socio-economic inequity in demand for insecticide-treated nets, in-door residual house spraying, larviciding and fogging in Sudan
Authors: Onwujekwe Obinna , Malik El-Fatih Mohamed , Mustafa Sara Hassan , Mnzava Abraham
Published: December 2005

Background

In order to optimally prioritize and use public and private budgets for equitable malaria vector control, there is a need to determine the level and determinants of consumer demand for different vector control tools.

Objectives

To determine the demand from people of different socio-economic groups for indoor residual house-spraying (IRHS), insecticide-treated nets (ITNs), larviciding with chemicals (LWC), and space spraying/fogging (SS) and the disease control implications of the result.

Methods

Ratings and levels of willingness-to-pay (WTP) for the vector control tools were determined using a random cross-sectional sample of 720 householdes drawn from two states. WTP was elicited using the bidding game. An asset-based socio-economic status (SES) index was used to explore whether WTP was related to SES of the respondents.

Results

IRHS received the highest proportion of highest preferred rating (41.0%) followed by ITNs (23.1%). However, ITNs had the highest mean WTP followed by IRHS, while LWC had the least. The regression analysis showed that SES was positively and statistically significantly related to WTP across the four vector control tools and that the respondents' rating of IRHS and ITNs significantly explained their levels of WTP for the two tools.

Conclusion

People were willing to pay for all the vector-control tools, but the demand for the vector control tools was related to the SES of the respondents. Hence, it is vital that there are public policies and financing mechanisms to ensure equitable provision and utilisation of vector control tools, as well as protecting the poor from cost-sharing arrangements.
Plasmodium yoelii 17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum
Authors: Sarfo Bismark Y , Armah Henry B , Irune Ikovwaiza , Adjei Andrew A , Olver Christine S , Singh Shailesh , Lillard James W , Stiles Jonathan K
Published: December 2005

Background

Malaria afflicts 300–500 million people causing over 1 million deaths globally per year. The immunopathogenesis of malaria is mediated partly by co mplex cellular and immunomodulator interactions involving co-regulators such as cytokines and adhesion molecules. However, the role of chemokines and their receptors in malaria immunopathology remains unclear. RANTES (Regulated on Activation Normal T-Cell Expressed and Secreted) is a chemokine involved in the generation of inflammatory infiltrates. Recent studies indicate that the degradation of cell-cell junctions, blood-brain barrier dysfunction, recruitment of leukocytes and Plasmodium-infected erythrocytes into and occlusion of microvessels relevant to malaria pathogenesis are associated with RANTES expression. Additionally, activated lymphocytes, platelets and endothelial cells release large quantities of RANTES, thus suggesting a unique role for RANTES in the generation and maintenance of the malaria-induced inflammatory response. The hypothesis of this study is that RANTES and its corresponding receptors (CCR1, CCR3 and CCR5) modulate malaria immunopathogenesis. A murine malaria model was utilized to evaluate the role of this chemokine and its receptors in malaria.

Methods

The alterations in immunomodulator gene expression in brains of Plasmodium yoelii 17XL-infected mice was analysed using cDNA microarray screening, followed by a temporal comparison of mRNA and protein expression of RANTES and its corresponding receptors by qRT-PCR and Western blot analysis, respectively. Plasma RANTES levels was determined by ELISA and ultrastructural studies of brain sections from infected and uninfected mice was conducted.

Results

RANTES (p < 0.002), CCR1 (p < 0.036), CCR3 (p < 0.033), and CCR5 (p < 0.026) mRNA were significantly upregulated at peak parasitaemia and remained high thereafter in the experimental mouse model. RANTES protein in the brain of infected mice was upregulated (p < 0.034) compared with controls. RANTES plasma levels were significantly upregulated; two to three fold in infected mice compared with controls (p < 0.026). Some d istal microvascular endothelium in infected cerebellum appeared degraded, but remained intact in controls.

Conclusion

The upregulation of RANTES, CCR1, CCR3, and CCR5 mRNA, and RANTES protein mediate inflammation and cellular degradation in the cerebellum during P. yoelii 17XL malaria.
Use of different but overlapping determinants in a retrovirus receptor accounts for non-reciprocal interference between xenotropic and polytropic murine leukemia viruses
Authors: Van Hoeven Neal S , Miller A Dusty
Published: December 2005

Background

Retrovirus infection depends on binding of the retroviral envelope (Env) protein to specific cell-surface protein receptors. Interference, or superinfection resistance, is a frequent consequence of retroviral infection, and occurs when newly-synthesized Env binds to receptor proteins resulting in a block to entry by retroviruses that use the same receptors. Three groups of viruses demonstrate a non-reciprocal pattern of interference (NRI), which requires the existence of both a common receptor utilized by all viruses within the group, and a specific receptor that is used by a subset of viruses. In the case of amphotropic and 10A1 murine leukemia viruses (MLV), the common and specific receptors are the products of two related genes. In the case of avian sarcoma and leukosis virus types B, D, and E, the two receptors are distinct protein products of a single gene. NRI also occurs between xenotropic and polytropic MLV. The common receptor, Xpr1, has been identified, but a specific receptor has yet to be described.

Results

Using chimeric receptor proteins and interference studies, we have identified a region of Xpr1 that is uniquely utilized by xenotropic MLV and show that this receptor domain is required for non-reciprocal interference.

Conclusion

We propose a novel pattern of receptor usage by xenotropic and polytropic MLV to explain the NRI observed between these viruses. We propose that the specific and common receptor determinants for xenotropic and polytropic viruses are simultaneously present in discreet domains of a single Xpr1 protein.
Detection of Cold Pain, Cold Allodynia and Cold Hyperalgesia in Freely Behaving Rats
Authors: Allchorne Andrew J , Broom Daniel C , Woolf Clifford J
Published: December 2005

Background:

Pain is elicited by cold, and a major feature of many neuropathic pain states is that normally innocuous cool stimuli begin to produce pain (cold allodynia). To expand our understanding of cold induced pain states we have studied cold pain behaviors over a range of temperatures in several animal models of chronic pain.

Results:

We demonstrate that a Peltier-cooled cold plate with ± 1°C sensitivity enables quantitative measurement of a detection withdrawal response to cold stimuli in unrestrained rats. In naïve rats the threshold for eliciting cold pain behavior is 5°C. The withdrawal threshold for cold allodynia is 15°C in both the spared nerve injury and spinal nerve ligation models of neuropathic pain. Cold hyperalgesia is present in the spared nerve injury model animals, manifesting as a reduced latency of withdrawal response threshold at temperatures that elicit cold pain in naïve rats. We also show that following the peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant, a hypersensitivity to cold occurs.

Conclusion:

The peltier-cooled provides an effective means of assaying cold sensitivity in unrestrained rats. Behavioral testing of cold allodynia, hyperalgesia and pain will greatly facilitate the study of the neurobiological mechanisms involved in cold/cool sensations and enable measurement of the efficacy of pharmacological treatments to reduce these symptoms.
Sequence analysis of Drd2, Drd4, and Dat1 in SHR and WKY rat strains
Authors: Mill Jonathan , Sagvolden Terje , Asherson Philip
Published: December 2005

Background

The Spontaneously Hypertensive Rat (SHR) shows a number of behaviours that closely parallel those seen in children with attention-deficit hyperactivity disorder. These include motor hyperactivity, excessive responses under a fixed-interval/extinction schedule, difficulty in acquiring operant tasks and increased sensitivity to immediate behavioural reinforcement. As in children with ADHD, the behavioural and cognitive deficits in the SHR are responsive to stimulants, including d-amphetamine and d,l-methylphenidate. The non-hyperactive Wistar Kyoto (WKY) rat strain is often used as a control in behavioural studies of the SHR, and WKY itself has been suggested to be a useful animal model of depression. Numerous studies have shown that dopaminergic neurotransmission is altered between the two strains. Human genetic studies have found associations between several dopaminergic genes and both ADHD and depression.

Methods

We sequenced three candidate dopaminergic genes (Drd2, Drd4, and Dat1) in the SHR and WKY to identify between-strain sequence differences.

Results

No between-strain sequence differences were found in either Drd2 or Drd4, but several variations were found in the Dat1 gene that encodes the dopamine transporter.

Conclusion

It is plausible that DNA sequence changes in the Dat1 gene account for some of the behavioural differences observed between the SHR and WKY strains. Future work will focus on elucidating the functional effects of the observed polymorphisms.
Fast-track applications: The potential for direct delivery of proteins and nucleic acids to plant cells for the discovery of gene function
Authors: Roberts Michael R
Published: December 2005

In animal systems, several methods exist for the direct delivery of nucleic acids and proteins into cells for functional analysis. Until recently, these methods have not been applied to plant systems. Now, however, several preliminary reports suggest that both nucleic acids and proteins can also be delivered into plant cells by very simple, direct application. This promises to open the way for high-throughput screening for gene function in a range of plant species.
Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer
Authors: Lee Sangjun , Mohsin Syed K , Mao Sufeng , Hilsenbeck Susan G , Medina Dan , Allred D Craig
Published: December 2005

Introduction

The hyperplastic enlarged lobular unit (HELU) is a common alteration in adult female human breast and is the earliest histologically identifiable lesion with premalignant potential. Growth and differentiation in normal epithelium are regulated by estrogen and progesterone, whose effects are mediated through estrogen receptor (ER)-α and progesterone receptor (PR). We assessed correlations between growth (proliferation and apoptosis), endogenous hormone levels (using age as a surrogate for menopausal/estrogen status), and ER-α/PR expression in HELUs versus adjacent normal terminal duct lobular units (TDLUs) to gain insight into potentially premalignant hyperplasia.

Methods

Proliferation (Ki67 antigen), ER-α, and PR were assessed by immunohistochemistry, apoptosis using the TUNEL (terminal transferase-mediated dUTP nick end-labeling) assay, and nuclear colocalization of ER-α and Ki67 by dual-labeled immunofluorescence in HELUs and adjacent TDLUs (n = 100–584, depending on the factor) from 324 breasts. All factors were quantified under direct microscopic visualization. ER-α/PR expression was semiquantified by estimating the proportion of positive cells (0 = none, 1 = <1/100, 2 = 1/100 to 1/10, 3 = 1/10 to 1/3, 4 = 1/3 to 2/3, and 5 = >2/3). Ki67, TUNEL, and colocalization of ER-α and Ki67 were scored by absolute counting (%positive).

Results

ER-α and PR expression were significantly elevated in HELUs versus adjacent TLDUs (average score: 4.5 versus 3.1 and 3.5 versus 2.1; P < 0.0001). Proliferation was also significantly higher in HELUs versus TDLUs (average 6.3% versus 2.0%; P < 0.0001). In contrast, apoptosis was significantly lower in HELUs versus TDLUs (average 0.61% versus 0.22%; P < 0.0001). Changes in proliferation and receptor expression were similar between premenopausal and postmenopausal TDLUs and HELUs, suggesting that hyperplastic cells remain responsive to regulation by estrogen. The proportion of ER-positive/proliferating cells was much higher in HELUs than TDLUs (27.6% vs. 4.9%; P < .0001).

Conclusion

Development of HELUs is associated with increased proliferation and decreased cell death relative to normal cells. ER-α and PR are highly elevated in HELUs, which may contribute to the hyperplasia because they mediate hormonal regulation of growth. An understanding of the fundamental causes of increased levels of receptors and growth may lead to new strategies to prevent breast cancer.
Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart
Authors: Mao Rong , Wang Xiaowen , Spitznagel Edward L , Frelin Laurence P , Ting Jason C , Ding Huashi , Kim Jung-whan , Ruczinski Ingo , Downey Thomas J , Pevsner Jonathan
Published: December 2005

Background

Down syndrome, caused by trisomic chromosome 21, is the leading genetic cause of mental retardation. Recent studies demonstrated that dosage-dependent increases in chromosome 21 gene expression occur in trisomy 21. However, it is unclear whether the entire transcriptome is disrupted, or whether there is a more restricted increase in the expression of those genes assigned to chromosome 21. Also, the statistical significance of differentially expressed genes in human Down syndrome tissues has not been reported.

Results

We measured levels of transcripts in human fetal cerebellum and heart tissues using DNA microarrays and demonstrated a dosage-dependent increase in transcription across different tissue/cell types as a result of trisomy 21. Moreover, by having a larger sample size, combining the data from four different tissue and cell types, and using an ANOVA approach, we identified individual genes with significantly altered expression in trisomy 21, some of which showed this dysregulation in a tissue-specific manner. We validated our microarray data by over 5,600 quantitative real-time PCRs on 28 genes assigned to chromosome 21 and other chromosomes. Gene expression values from chromosome 21, but not from other chromosomes, accurately classified trisomy 21 from euploid samples. Our data also indicated functional groups that might be perturbed in trisomy 21.

Conclusions

In Down syndrome, there is a primary transcriptional effect of disruption of chromosome 21 gene expression, without a pervasive secondary effect on the remaining transcriptome. The identification of dysregulated genes and pathways suggests molecular changes that may underlie the Down syndrome phenotypes.
Differential Expression and Processing of Chromogranin A and Secretogranin II in Relation to the Secretory Status of Endocrine Cells
Authors: Peinado J. R. , Vazquez-Martinez R. , Cruz-García D. , Ruiz-Navarro A. , Anouar Y. , Tonon M. C. , Vaudry H. , Gracia-Navarro F. , Castano J. P. , Malagón M. M.
Published: December 2005

Chromogranin A (CgA) and secretogranin II (SgII) are neuroendocrine secretory proteins that participate in regulation of the secretory pathway and also serve as precursors of biologically active peptides. To investigate whether there is a relationship between the expression, distribution, and processing of CgA and SgII and the degree of secretory activity, we employed two melanotrope subpopulations of the pituitary intermediate lobe that exhibit opposite secretory phenotypes. Thus, although one of the melanotrope subtypes shows high secretory activity, the other exhibits characteristics of a hormone storage phenotype. Our data show that SgII expression levels were higher in secretory melanotropes, whereas CgA expression showed similar rates in both cell subsets. The use of various antibodies revealed the presence of the unprocessed proteins as well as three CgA-derived peptides (67, 45, and 30 kDa) and six SgII-derived peptides (81, 66, 55, 37, 32, and 30 kDa) in both subpopulations. However, the smallest molecular forms of both granins predominated in secretory melanotropes, whereas the largest SgII- and CgA-immunoreactive peptides were more abundant in storage melanotropes, which is suggestive of a more extensive processing of granins in the secretory subset. Confocal microscopy studies showed that CgA immunoreactivity was higher in storage cells, but SgII immunoreactivity was higher in secretory melanotropes. Taken together, our results indicate that SgII and CgA are differentially regulated in melanotrope subpopulations. Thus, SgII expression is strongly related to the secretory activity of melanotrope cells, whereas CgA expression may not be related to secretory rate, but, rather, to hormone storage in this endocrine cell type.
Crack STIT tessellations: characterization of stationary random tessellations stable with respect to iteration
Authors: Nagel Werner , Weiss Viola
Published: December 2005

Our main result is the proof of the existence of random stationary tessellations in d-dimensional Euclidean space with the following stability property: their distribution is invariant with respect to the operation of iteration (or nesting) of tessellations with an appropriate rescaling. This operation means that the cells of a given tessellation are individually and independently subdivided by independent, identically distributed tessellations, resulting in a new tessellation. It is also shown that, for any stationary tessellation, the sequence that is generated by repeated rescaled iteration converges weakly to such a stable tessellation; thus, the class of all stable stationary tessellations is fully characterized.
Random dynamics and thermodynamic limits for polygonal Markov fields in the plane
Authors: Schreiber Tomasz
Published: December 2005

We construct random dynamics for collections of nonintersecting planar contours, leaving invariant the distributions of length- and area-interacting polygonal Markov fields with V-shaped nodes. The first of these dynamics is based on the dynamic construction of consistent polygonal fields, as presented in the original articles by Arak (1983) and Arak and Surgailis (1989), (1991), and it provides an easy-to-implement Metropolis-type simulation algorithm. The second dynamics leads to a graphical construction in the spirit of Fernándezet al.(1998), (2002) and yields a perfect simulation scheme in a finite window in the infinite-volume limit. This algorithm seems difficult to implement, yet its value lies in that it allows for theoretical analysis of the thermodynamic limit behaviour of length-interacting polygonal fields. The results thus obtained include, in the class of infinite-volume Gibbs measures without infinite contours, the uniqueness and exponential α-mixing of the thermodynamic limit of such fields in the low-temperature region. Outside this class, we conjecture the existence of an infinite number of extreme phases breaking both the translational and rotational symmetries.
A class of self-similar random measure
Authors: Vere-Jones David
Published: December 2005

We describe a class of self-similar random measure that generalizes the class of stable, completely random measure, or, in one dimension, the class of processes with stable independent increments. As with the stable processes, the realizations are purely atomic, but the masses of the atoms are not necessarily independent, but rather characterized by self-similar dependence relations. Indeed, the class can be described most effectively in terms of the point process on the product space for the locations and sizes (‘marksȉ) of the atoms. Then self-similarity reduces to an invariance relation (‘biscale invariance’) on the distribution of this marked point process. The condition can be satisfied when the marked point process is compound Poisson, corresponding to the nonnegative stable processes, but is by no means restricted to this case. An example is given which modifies and extends Ogata's epidemic-type aftershock sequence model for earthquake occurrence.
Dynamic admission control for loss systems with batch arrivals
Authors: Örmeci E. L. , Burnetas A.
Published: December 2005

We consider the problem of dynamic admission control in a Markovian loss system with two classes. Jobs arrive at the system in batches; each admitted job requires different service rates and brings different revenues depending on its class. We introduce the definition of a ‘preferred class’ for systems receiving mixed and single-class batches separately, and derive sufficient conditions for each system to have a preferred class. We also establish a monotonicity property of the optimal value functions, which reduces the number of possibly optimal actions.
Uniqueness criteria for continuous-time Markov chains with general transition structures
Authors: Chen Anyue , Pollett Phil , Zhang Hanjun , Cairns Ben
Published: December 2005

We derive necessary and sufficient conditions for the existence of bounded or summable solutions to systems of linear equations associated with Markov chains. This substantially extends a famous result of G. E. H. Reuter, which provides a convenient means of checking various uniqueness criteria for birth-death processes. Our result allows chains with much more general transition structures to be accommodated. One application is to give a new proof of an important result of M. F. Chen concerning upwardly skip-free processes. We then use our generalization of Reuter's lemma to prove new results for downwardly skip-free chains, such as the Markov branching process and several of its many generalizations. This permits us to establish uniqueness criteria for several models, including the general birth, death, and catastrophe process, extended branching processes, and asymptotic birth-death processes, the latter being neither upwardly skip-free nor downwardly skip-free.
Light-tailed asymptotics of stationary probability vectors of Markov chains of GI/G/1 type
Authors: Li Quan-Lin , Zhao Yiqiang Q.
Published: December 2005

In this paper, we consider the asymptotic behavior of stationary probability vectors of Markov chains of GI/G/1 type. The generating function of the stationary probability vector is explicitly expressed by the R-measure. This expression of the generating function is more convenient for the asymptotic analysis than those in the literature. The RG-factorization of both the repeating row and the Wiener-Hopf equations for the boundary row are used to provide necessary spectral properties. The stationary probability vector of a Markov chain of GI/G/1 type is shown to be light tailed if the blocks of the repeating row and the blocks of the boundary row are light tailed. We derive two classes of explicit expression for the asymptotic behavior, the geometric tail, and the semigeometric tail, based on the repeating row, the boundary row, or the minimal positive solution of a crucial equation involved in the generating function, and discuss the singularity classes of the stationary probability vector.
A probabilistic model for the survivability of cells
Authors: Adler Ilan , Ahn Hyun-Soo , Karp Richard M. , Ross Sheldon M.
Published: December 2005

Consider n cells, of which some are target cells, and suppose that each cell has a weight. The cells are killed in a sequential manner, with each currently live cell being the next one killed with a probability proportional to its weight. We study the distribution of the number of cells that are alive at the moment when all the target cells have been killed.
An epidemic model with exposure-dependent severities
Authors: Ball Frank , Britton Tom
Published: December 2005

We consider a stochastic model for the spread of a susceptible–infective–removed (SIR) epidemic among a closed, finite population, in which there are two types of severity of infectious individuals, namely mild and severe. The type of severity depends on the amount of infectious exposure an individual receives, in that infectives are always initially mild but may become severe if additionally exposed. Large-population properties of the model are derived. In particular, a coupling argument is used to provide a rigorous branching process approximation to the early stages of an epidemic, and an embedding argument is used to derive a strong law and an associated central limit theorem for the final outcome of an epidemic in the event of a major outbreak. The basic reproduction number, which determines whether or not a major outbreak can occur given few initial infectives, depends only on parameters of the mild infectious state, whereas the final outcome in the event of a major outbreak depends also on parameters of the severe state. Moreover, the limiting final size proportions need not even be continuous in the model parameters.
How to estimate the rate function of a cumulative process
Authors: Duffy Ken , Metcalfe Anthony P.
Published: December 2005

Consider two sequences of bounded random variables, a value and a timing process, that satisfy the large deviation principle (LDP) with rate function J(⋅,⋅) and whose cumulative process satisfies the LDP with rate function I(⋅). Under mixing conditions, an LDP for estimates of I constructed by transforming an estimate of J is proved. For the case of a cumulative renewal process it is demonstrated that this approach is favourable to a more direct method, as it ensures that the laws of the estimates converge weakly to a Dirac measure at I.
A uniformly convergent adaptive particle filter
Authors: Papavasiliou Anastasia
Published: December 2005

Particle filters are Monte Carlo methods that aim to approximate the optimal filter of a partially observed Markov chain. In this paper, we study the case in which the transition kernel of the Markov chain depends on unknown parameters: we construct a particle filter for the simultaneous estimation of the parameter and the partially observed Markov chain (adaptive estimation) and we prove the convergence of this filter to the correct optimal filter, as time and the number of particles go to infinity. The filter presented here generalizes Del Moral's Monte Carlo particle filter.
Queues, stores, and tableaux
Authors: Draief Moez , Mairesse Jean , O'Connell Neil
Published: December 2005

Consider the single-server queue with an infinite buffer and a first-in–first-out discipline, either of type M/M/1 or Geom/Geom/1. Denote by 𝒜 the arrival process and by s the services. Assume the stability condition to be satisfied. Denote by 𝒟 the departure process in equilibrium and by r the time spent by the customers at the very back of the queue. We prove that (𝒟, r) has the same law as (𝒜, s), which is an extension of the classical Burke theorem. In fact, r can be viewed as the sequence of departures from a dual storage model. This duality between the two models also appears when studying the transient behaviour of a tandem by means of the Robinson–Schensted–Knuth algorithm: the first and last rows of the resulting semistandard Young tableau are respectively the last instant of departure from the queue and the total number of departures from the store.
Sharp reliability bounds for the ℒ-like distributions, a class in which ageing is based on Laplace transform inequalities
Authors: Hu Chin-Yuan , Lin Gwo Dong
Published: December 2005

We establish Klar's (2002) conjecture about sharp reliability bounds for life distributions in the ℒα-class in reliability theory. The key idea is to construct a set of two-point distributions whose support points satisfy a certain system of equalities and inequalities.
The conserved oligomeric Golgi complex acts in organ morphogenesis via glycosylation of an ADAM protease inC. elegans
Authors: Kubota Yukihiko , Sano Mitsue , Goda Saori , Suzuki Norio , Nishiwaki Kiyoji
Published: December 2005

In C. elegans, the gonad acquires two U-shaped arms through directed migration of gonadal distal tip cells (DTCs). A member of the ADAM (a disintegrin and metalloprotease) family, MIG-17, is secreted from muscle cells and localizes to the gonadal basement membrane where it functions in DTC migration. Mutations in cogc-3 and cogc-1 cause misdirected DTC migration similar to that seen in mig-17 mutants. Here, we report that COGC-3 and COGC-1 proteins are homologous to mammalian COG-3/Sec34 and COG-1/ldlBp, respectively, two of the eight components of the conserved oligomeric Golgi (COG) complex required for Golgi function. Knockdown of any of the other six components by RNA interference also produces DTC migration defects, suggesting that the eight components function in a common pathway. COGC-3 and COGC-1 are required for the glycosylation and gonadal localization of MIG-17, but not for secretion of MIG-17 from muscle cells. Furthermore,COGC-3 requires MIG-17 activity for its action in DTC migration. Our findings demonstrate that COG complex-dependent glycosylation of an ADAM protease plays a crucial role in determining organ shape.
Generic and Brand Advertising Strategies in a Dynamic Duopoly
Authors: Bass Frank M. , Krishnamoorthy Anand , Prasad Ashutosh , Sethi Suresh P.
Published: December 2005

To increase the sales of their products through advertising, firms must integrate their brand-advertising strategy for capturing market share from competitors and their generic-advertising strategy for increasing primary demand for the category. This paper examines whether, when, and how much brand advertising versus generic advertising should be done. Using differential game theory, optimal advertising decisions are obtained for a dynamic duopoly with symmetric or asymmetric competitors. We show how advertising depends on the cost and effectiveness of each type of advertising for each firm, the allocation of market expansion benefits, and the profit margins determined endogenously from price competition. We find that generic advertising is proportionally more important in the short term and that there are free-riding effects leading to suboptimal industry expenditure on generic advertising that worsen as firms become more symmetric. Due to free-riding by the weaker firm, its instantaneous profit and market share can actually be higher. The effectiveness of generic advertising and the allocation of its benefits, however, have little effect on the long-run market shares, which are determined by brand-advertising effectiveness. Extensions of the model show that market potential saturation leads to a decline in generic advertising over time.
Prediction in Marketing Using the Support Vector Machine
Authors: Cui Dapeng , Curry David
Published: December 2005

Many marketing problems require accurately predicting the outcome of a process or the future state of a system. In this paper, we investigate the ability of the support vector machine to predict outcomes in emerging environments in marketing, such as automated modeling, mass-produced models, intelligent software agents, and data mining. The support vector machine (SVM) is a semiparametric technique with origins in the machine-learning literature of computer science. Its approach to prediction differs markedly from that of standard parametric models. We explore these differences and benchmark the SVM's prediction hit-rates against those from the multinomial logit model. Because there are few applications of the SVM in marketing, we develop a framework to position it against current modeling techniques and to assess its weaknesses as well as its strengths.
Transactive Memory Systems, Learning, and Learning Transfer
Authors: Lewis Kyle , Lange Donald , Gillis Lynette
Published: December 2005

Knowledge embedded in a group’s structures and processes can be leveraged to create sustainable advantage for organizations. We propose that knowledge embedded with a transactive memory system (TMS) helps groups apply prior learning to new tasks and develop an abstract understanding of a problem domain, leading to sustained performance. We present a framework for understanding TMSs as learning systems that affect group learning and learning transfer, and we test the major outcomes of the framework in an empirical study. We found that groups with a prior TMS and experience with two tasks in the same domain were more likely to develop an abstract understanding of the principles relevant to the task domain—a critical factor for learning transfer in general. We did not, however, find strong support for our contention that a TMS facilitates learning transfer after experience with only a single task. Further examinations of our findings showed that the extent to which members maintained expertise across tasks influenced the degree of learning transfer, especially for groups whose members had previously developed a TMS with another group. Our findings show that a TMS has broader benefits beyond the task for which it first developed because a TMS affects members’ ability to apply prior learning and develop a collective, abstract understanding of the task domain. More generally, our study demonstrates that TMSs influence group learning and learning transfer. We discuss our study’s implications for practice and for TMS and group learning theories.
The new role of D-dimer as a predictor of recurrent venous thromboembolism D-Dimere: Ihre neue Rolle als Prädiktoren für rezidivierende venöse Thromboembolien
Authors: Cosmi Benilde , Palareti Gualtiero
Published: December 2005

Venous thromboembolism (VTE) tends to recur after oral anticoagulant therapy (OAT) withdrawal, regardless of the duration of treatment. As a result, the optimal duration of OAT after VTE is still a matter of debate. Patients are currently stratified in risk categories for recurrence on the basis of the clinical characteristics of the index event. Distal deep vein thrombosis (DVT) or VTE due to a transient risk factor are associated with a low risk of recurrence and a brief three-month course of anticoagulation is usually recommended. An event which is either idiopathic or with known thrombophilic defects, such as FV Leiden or the G20120A prothrombin mutation, is associated with a high risk of recurrence and an OAT course of at least six months is recommended.

More recently, D-dimer (D-d) levels have been shown to be additional risk factors for recurrence. D-d has been evaluated both during OAT and after its withdrawal. In some patients, after VTE D-d levels are persistently elevated during anticoagulation in spite of apparently adequate antithrombotic treatment, which could indicate insufficient anticoagulation. D-d is more frequently altered during anticoagulation in patients with idiopathic or cancer-associated VTE than with secondary VTE. After idiopathic DVT, the time spent at near normal International Normalized Ratio (INR) values (<1.5) during the first three months of OAT is associated with higher D-d values measured during OAT and after its interruption and is a significant risk factor for late VTE recurrences. Moreover, altered D-d significantly increases the risk of recurrence associated with inherited thrombophilic conditions, while residual venous obstruction does not increase the risk of recurrence associated with abnormal D-d. Results of a management study (PROLONG study) indicate that subjects with negative D-d at one month after OAT withdrawal have a low risk of recurrence, while those with altered D-d have a significantly higher risk and deserve prolonged OAT treatment.
ZNS-Proteine im Liquor: Einflussfaktoren auf ihre Konzentration im Liquor und klinische Relevanz Brain specific proteins in cerebrospinal fluid (CSF): factors influencing their concentration in CSF and clinical relevance
Authors: Tumani Hayrettin , Brettschneider Johannes
Published: December 2005

Lösliche ZNS-Proteine können als Marker für Krankheitsaktivität und die Beurteilung von Therapieeffekten nützlich sein. Die Kenntnis der Herkunft der ZNS-Proteine erlaubt es, zellspezifische Reaktionen zu erkennen und Pathomechanismen genauer zu studieren.

Der Liquorraum wird vom vaskulären System getrennt durch die Blut-Liquor-Schranke. Zuverlässigster Laborparameter für die Beurteilung der Blut-Liquor-Schranke ist der Liquor/Serum-Konzentrationsquotient des Albumins (Qalb). Eine Erhöhung des Qalb als Ausdruck einer “Dysfunktion” der Blut-Liquor-Schranke findet sich bei unterschiedlichen neurologischen Erkrankungen. Als zugrunde liegende Pathomechanismen werden eine Verlangsamung der Liquorzirkulation und ein Anstieg der Permeabilität an den Liquor-nahen Kapillaren diskutiert. Das ausschließlich aus dem ZNS stammende Liquorprotein Beta-Trace kann einen Beitrag zur Klärung des Pathomechanismus von Schrankenstörungen unklarer Ätiologie leisten. Die Konzentration der ZNS-Proteine im Liquor läßt keinen Zusammenhang mit der Molekülgröße bzw. dem Molekulargewicht erkennen. Dagegen kann die Lokalisation eines pathologischen Prozesses im Gehirn die Konzentration von Liquorproteinen wesentlich beeinflussen. Bestimmte Regionen des Gehirns, z.B. frontale, parietale oder occipitale Rindenareale gelten als Liquor-fern. Entzündliche Prozesse in diesen Regionen können mit einem normalen lumbalen Liquorbefund einhergehen. Am Beispiel des Tau-Proteins und anderer Liquorproteine wurde gezeigt, dass Liquorproteine neuronalen und glialen Ursprungs bei sehr unterschiedlichen Erkrankungen pathologisch erhöhte Konzentrationen aufweisen können. Diese fehlende Spezifität der Liquorproteine schränkt die klinische Relevanz deutlich ein. Andererseits zeigten insbesondere Untersuchungen zur Liquordiagnostik dementieller Erkrankungen, dass krankheitsspezifische Informationen durch Liquorproteine dann möglich sind, wenn Kombinationen mehrerer Parameter untersucht werden.
Die Wertigkeit der quantitativen und qualitativen IgG Analyse im Liquor Quality rating of quantitative and qualitative IgG analysis in liquor
Authors: Mayringer Irmgard , Deisenhammer Florian
Published: December 2005

Die intrathekale IgG Synthese kann zum einen quantitativ und zum anderen qualitativ nachgewiesen werden und ist oftmals ein wichtiges Kriterium zur endgültigen Diagnosestellung vor allem bei demyelinisierenden Erkrankungen des zentralen Nervensystems (z. B. der Multiplen Sklerose). Die qualitative IgG Bestimmung mittels isoelektrischer Fokussierung ist die Methode mit der höchsten Sensitivität und ist daher als erste Wahl zu empfehlen. Die quantitative Bestimmung hat den Vorteil der wesentlich rascheren Verfügbarkeit und kann im Falle eines positiven Ergebnisses als Nachweis einer intrathekalen IgG Synthese gewertet werden. In dieser Arbeit werden die gängigsten Methoden und ihre Wertigkeit in der neurologischen Labordiagnostik besprochen.
An Integrated Approach to the Determination and Consequences of Residual Stress on the Fatigue Performance of Welded Aircraft Structures
Authors: Edwards L , Fitzpatrick ME , Irving PE , Sinclair I , Zhang X , Yapp D
Published: December 2005

Although residual stress in welded structures and components has long been known to have an effect on their fatigue performance, access to reliable, spatially accurate residual stress field data has been limited. Recent advances in neutron and synchrotron X-ray diffraction allow a far more detailed picture of weld residual stress fields to be obtained that permits the development and use of predictive models that can be used for accurate design against fatigue in aircraft structures. This paper describes a fully integrated study of the three-dimensional residual stress distribution accompanying state-of-the-art fusion welds in 2024-T4 aluminum alloy, and how it is affected by subsequent machining and service loading. A particular feature of this work has been the development of techniques allowing the nondestructive evaluation of the residual stress field in the full range of specimens used to provide the design data required for welded aircraft structures and the integration of this information into all aspects of damage tolerant design.
Trends in High Temperature Structural Integrity Assessment
Authors: Webster GA
Published: December 2005

Failure in components that may contain defects and that operate at elevated temperatures can occur by creep, fatigue, or fast fracture, or some combination of these processes. Frequently, these components include welds and repairs to welds. Codes and standards are available for assessing the structural integrity of these types of components. This paper addresses the main issues of concern in making safety assessments and reliable lifetime predictions for situations where creep processes dominate. Emphasis is placed on the creep component of cracking. Initially, models of crack initiation and growth are reviewed. The creep fracture mechanics parameter C* is used to make predictions. The influence of constraint on the mechanisms responsible for void nucleation and growth is considered and creep crack growth rate laws derived. Methods of calculating C* in components from the plastic fracture mechanics parameter J or, approximately, from stress intensity factor K and limit analysis using reference stress concepts are described. A procedure for making remaining life assessments for cracking into progressively deteriorating material is considered. Techniques for dealing with an initial transient phase, or incubation period, during which damage builds up at a crack tip are presented. An indication of the scatter to be expected in creep crack growth data, for use in sensitivity studies, is provided. The role of residual stress on the early stages of cracking and subsequent crack propagation is discussed.