bluuebunny/crossref_metadata_2025 huggingface dataset:
Fish Consumption and Incidence of Stroke
Authors: He Ka , Song Yiqing , Daviglus Martha L. , Liu Kiang , Van Horn Linda , Dyer Alan R. , Goldbourt Uri , Greenland Philip
Published: May 2004

Background and Purpose—

Results from observational studies on fish consumption and risk of stroke are inconsistent. We quantitatively assessed the relationship between fish intake and incidence of stroke using a meta-analysis of cohort studies.

Methods—

We searched the Medline and Embase databases (1966 through October 2003) and identified 9 independent cohorts (from 8 studies) that provided a relative risk (RR) and corresponding 95% CI for total or any type of stroke in relation to fish consumption. Pooled RR and 95% CI of stroke were estimated by variance-based meta-analysis.

Results—

Compared with those who never consumed fish or ate fish less than once per month, the pooled RRs for total stroke were 0.91 (95% CI, 0.79 to 1.06) for individuals with fish intake 1 to 3 times per month, 0.87 (95% CI, 0.77 to 0.98) for once per week, 0.82 (95% CI, 0.72 to 0.94) for 2 to 4 times per week, and 0.69 (95% CI, 0.54 to 0.88) for ≥5 times per week (
P
for trend=0.06). In stratified analyses of 3 large cohort studies with data on stroke subtypes, the pooled RRs across 5 categories of fish intake were 1.0, 0.69 (95% CI, 0.48 to 0.99), 0.68 (95% CI, 0.52 to 0.88), 0.66 (95% CI, 0.51 to 0.87), and 0.65 (95% CI, 0.46 to 0.93) for ischemic stroke (
P
for trend=0.24); and 1.0, 1.47 (95% CI, 0.81 to 2.69), 1.21 (95% CI, 0.78 to 1.85), 0.89 (95% CI, 0.56 to 1.40), and 0.80 (95% CI, 0.44 to 1.47) for hemorrhagic stroke (
P
for trend=0.31).

Conclusions—

These results suggest that intake of fish is inversely related to risk of stroke, particularly ischemic stroke. Fish consumption as seldom as 1 to 3 times per month may protect against the incidence of ischemic stroke.
Comparison of Perfusion Computed Tomography and Computed Tomography Angiography Source Images With Perfusion-Weighted Imaging and Diffusion-Weighted Imaging in Patients With Acute Stroke of Less Than 6 Hours’ Duration
Authors: Schramm Peter , Schellinger Peter D. , Klotz Ernst , Kallenberg Kai , Fiebach Jochen B. , Külkens Sonja , Heiland Sabine , Knauth Michael , Sartor Klaus
Published: May 2004

Background and Purpose—

We aimed to determine the diagnostic value of perfusion computed tomography (PCT) and CT angiography (CTA) including CTA source images (CTA-SI) in comparison with perfusion-weighted magnetic resonance imaging (MRI) (PWI) and diffusion-weighted MRI (DWI) in acute stroke <6 hours.

Methods—

Noncontrast-enhanced CT, PCT, CTA, stroke MRI, including PWI and DWI, and MR angiography (MRA), were performed in patients with symptoms of acute stroke lasting <6 hours. We analyzed ischemic lesion volumes on patients’ arrival as shown on NECT, PCT, CTA-SI, DWI, and PWI (Wilcoxon, Spearman, Bland-Altman) and compared them to the infarct extent as shown on day 5 NECT.

Results—

Twenty-two stroke patients underwent CT and MRI scanning within 6 hours. PCT time to peak (PCT-TTP) volumes did not differ from PWI-TTP (
P
=0.686 for patients who did not undergo thrombolysis/
P
=0.328 for patients who underwent thrombolysis), nor did PCT cerebral blood volume (PCT-CBV) differ from PWI-CBV (
P
=0.893/
P
=0.169). CTA-SI volumes did not differ from DWI volumes (
P
=0.465/
P
=0.086). Lesion volumes measured in PCT maps significantly correlated with lesion volumes on PWI (
P
=0.0047,
r
=1.0/
P
=0.0019,
r
=0.897 for TTP;
P
=0.0054,
r
=0.983/
P
=0.0026,
r
=0.871 for CBV). Also, PCT-CBV lesion volumes significantly correlated with follow-up CT lesion volumes (
P
=0.0047,
r
=1.0/
P
=0.0046,
r
=0.819).

Conclusions—

In hyperacute stroke, the combination of PCT and CTA can render important diagnostic information regarding the infarct extent and the perfusion deficit. Lesions on PCT-TTP and PCT-CBV do not differ from lesions on PWI-TTP and PWI-CBV; lesions on CTA source images do not differ from lesions on DWI. The combination of noncontrast-enhanced CT (NECT), perfusion CT (PCT), and CT angiography (CTA) can render additional information within <15 minutes and may help in therapeutic decision-making if PWI and DWI are not available or cannot be performed on specific patients.
Argatroban Anticoagulation in Patients With Acute Ischemic Stroke (ARGIS-1)
Authors: LaMonte Marian P. , Nash Marshall L. , Wang David Z. , Woolfenden Andrew R. , Schultz John , Hursting Marcie J. , Brown Philip M.
Published: May 2004

Background and Purpose—

Direct thrombin inhibitors, including argatroban, represent an anticoagulant class distinct from heparins. We investigated the safety of 2 levels of argatroban anticoagulation in acute ischemic stroke.

Methods—

This multicenter, randomized, double-blinded, placebo-controlled study included 171 patients with acute (≤12 hours from onset) stroke and National Institutes of Health Stroke Scale (NIHSS) scores of 5 to 22. Patients received continuous intravenous argatroban (100 μg/kg bolus) at 3 μg/kg per minute (n=59) or 1 μg/kg per minute (n=58), respectively, adjusted to target activated partial thromboplastin times (aPTTs) 2.25× and 1.75× baseline or placebo (n=54) for 5 days. The primary outcome was symptomatic intracranial hemorrhage (ICH) at 30 days.

Results—

Baseline characteristics including neurologic deficits (median NIHSS score 9) were comparable between groups. Argatroban at mean doses of 2.7 and 1.2 μg/kg per minute increased aPTTs significantly (
P
<0.001), with mean aPTTs at or near target values throughout infusion. Symptomatic ICH was not significantly different between groups (high-dose argatroban, 5.1%; low-dose argatroban, 3.4%; placebo, 0%;
P
≥0.18), with 3 events during argatroban infusion and 2 events ≥7 days after stopping infusion. No significant between-group differences occurred in asymptomatic ICH (7 events), major systemic hemorrhage (no event), or 90-day mortality (13.4% overall).

Conclusions—

In this first North American randomized, double-blinded, placebo-controlled study of direct thrombin inhibition in acute ischemic stroke, argatroban at each dose evaluated significantly prolonged aPTTs without increasing ICH or major bleeding. These results suggest that argatroban provides safe anticoagulation in acute ischemic stroke, warranting future studies powered to evaluate its efficacy and more precisely estimate event rates.
Cerebral Microbleeds
Authors: Jeerakathil Tom , Wolf Philip A. , Beiser Alexa , Hald John K. , Au Rhoda , Kase Carlos S. , Massaro Joseph M. , DeCarli Charles
Published: May 2004

Background and Purpose—

Cerebral microbleeds (CMBs) are areas of low signal intensity on gradient echo T2*-weighted magnetic resonance imaging (T2*MRI) corresponding to hemosiderin deposits in the perivascular space. Microangiopathy from atherosclerosis or amyloid angiopathy might lead to the formation of these lesions; therefore, there may be associations between CMBs and cardiovascular risk factors, APOE allele status, and brain morphology. We examined these relationships in the Framingham Study (FHS).

Methods—

In 472 subjects from the FHS Offspring and Cohort, we related CMB status to age, sex, systolic blood pressure, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels, smoking, diabetes, total hemispheric brain volume, white matter hyperintensity volume (WMHV), and APOE allele status.

Results—

Overall prevalence of CMBs was 4.7%, but CMBs were more prevalent with advanced age and male sex. Blood pressure, brain volume, and WMHV were related to CMBs in crude analysis but not after adjustment for age and sex. There were no significant relationships demonstrated between CMBs and APOE allele status, cholesterol, smoking, or diabetes.

Conclusions—

There is a low prevalence of CMBs in the community and a strong relationship with increasing age and male sex. We found no independent relationships with cardiovascular risk factors, APOE status, brain volumes, or WMH.
Two Solitudes: The Behaviour of Pigeons in Competitive Feeding
Authors: Sogbein  , Church  , Plowright  , Gagnon  , Potvin
Published: May 2004

Previous research showed that pigeons foraging for preferred grains of maize and less preferred grains of wheat respond to the presence of a competitor by becoming less choosy ( i.e. they more readily choose wheat). We extended this work by disentangling the presence of the competitor from the resource depletion associated with it. In Experiment 1, eight birds foraged for maize and wheat in a flight cage. They were tested both alone and with another bird in different foraging sessions. Two groups were formed and differed in how they were treated when the birds foraged in pairs: both birds had access to food (Both Eat) versus only one bird had access to food (Only One Eats) while the other was placed behind a transparent curtain. For the latter treatment, no effect of the mere presence of the other bird on choice was found. Pigeons were, however, less choosy in the presence of a real competitor that exploited the food. At the end of the experiment, the pigeons that had been tested in the 'Both Eat' treatment, were tested in the 'Only One Eats' treatment. They behaved as if foraging alone. Experiment 2 introduced a new condition in which one bird ate and the other was placed behind the curtain where it pecked at grain but could not eat it. Even though this other bird behaved as if it were a potential competitor, it had no effect on the forager in the pair. The only significant difference in choice proportions was between birds foraging in real competition ( i.e. where the other bird caused resource depletion) or not. In competitive feeding situations, pigeons react to what is most directly associated with the dwindling food conditions but are insensitive to the presence and to the pecking behaviour of the animal that creates them.
Opposite Changes in Plasma Testosterone and Corticosterone Levels Following a Simulated Territorial Challenge in Male Great Tits
Authors: Pinxten Rianne , Arckens Lutgarde , van Duyse Els , Eens Marcel , Darras Veerle
Published: May 2004

The apparent ability of plasma testosterone (T) and corticosterone (B) levels to fluctuate rapidly in response to agonistic interactions, suggests that these hormones may play an important role in an animal's acute behavioural response during such interactions. In the present study, free-living male great tits, Parus major, were subjected to a simulated territorial intrusion (STI) during the egg laying, incubation and nestling stage of first broods. Plasma T and B levels of challenged males were compared to those of control males matched for breeding stage, day in breeding stage, and time of day. Plasma B levels were significantly higher in challenged males compared to control males during the egg laying and incubation stage but not during the nestling stage. On the other hand, challenged males had significantly lower plasma T levels than control males throughout the breeding cycle. While having low plasma T and elevated plasma B levels, challenged males showed a vigorous and unrelenting territorial response to the STI. Plasma T and B levels of challenged males did not correlate with the intensity of the behavioural response to the STI. These findings do not agree with the predictions of the 'challenge hypothesis' that males exposed to a territorial challenge while having breeding baseline T levels will respond with an increase in T or that T correlates with the intensity of aggression during a challenge. Together, our findings suggest a role for B rather than T in the regulation of territorial defence in male great tits.
Epidemiology and Natural History of Acute Patellar Dislocation
Authors: Fithian Donald C. , Paxton Elizabeth W. , Stone Mary Lou , Silva Patricia , Davis Daniel K. , Elias David A. , White Lawrence M.
Published: May 2004

Background

The goals of this study were to (1) define the epidemiology of acute patellar dislocation, (2) determine the risk of subsequent patellar instability episodes (subluxation and/or redislocation) during the study period, and (3) identify risk factors for subsequent instability episodes.

Study Design

Prospective cohort study.

Methods

The authors prospectively followed 189 patients for a period of 2 to 5 years. Historical data, injury mechanisms, and physical and radiographic measurements were recorded to identify potential risk factors for poor outcomes.

Results

Risk was highest among females 10 to 17 years old. Patients presenting with a prior history of instability were more likely to be female (P < .05) and were older than first-time dislocation patients (P < .05). Fewer first-time dislocators (17%) had episodes of instability during follow-up than patients with a previous history of instability (49%) (P < .01). After adjusting for demographics, patients with a prior history had 7 times higher odds of subsequent instability episodes during follow-up than first time dislocators (adjusted odds ratio = 6.6, P < .001).

Conclusions

Patellar dislocators who present with a history of patellofemoral instability are more likely to be female, are older, and have greater risk of subsequent patellar instability episodes than first-time patellar dislocators. Risk of recurrent patellar instability episodes in either knee is much higher in this group than in first-time dislocators.
Rupture of the Pectoralis Major Muscle
Authors: Äärimaa Ville , Rantanen Jussi , Heikkilä Jouni , Helttula Ilmo , Orava Sakari
Published: May 2004

Background

Total or near-total rupture of the pectoralis major muscle is a rare injury. Fewer than 200 cases have been reported in literature, many of them in single case reports. There is discrepancy regarding whether this kind of injury should be treated operatively.

Hypothesis

Early surgical treatment is necessary to obtain optimal functional recovery following total or near-total ruptures of the pectoralis major muscle.

Study Design

A case series of 33 operatively treated pectoralis major ruptures combined with a meta-analysis of the previously published cases in the English literature.

Methods

The authors have retrospectively analyzed 33 operatively treated cases of total or near-total ruptures of the pectoralis major muscle. They have also analyzed the previously published cases and the final outcomes of their treatment. The difference in outcome between groups of acute operation, delayed operation, and conservative treatment in both their own material and meta-analysis was statistically analyzed.

Results

Both the case series and the analysis of the cases from the literature showed that early operative treatment is associated with better outcome than delayed treatment. The delayed operation was associated with better outcome than the conservative treatment.

Conclusion

Early surgical treatment by anatomic repair gives the best results in the treatment of total and near-total ruptures of the pectoralis major muscle.
Effects of Applied Quadriceps and Hamstrings Muscle Loads on Forces in the Anterior and Posterior Cruciate Ligaments
Authors: Markolf Keith L. , O'Neill Geoffery , Jackson Steven R. , McAllister David R.
Published: May 2004

Background

Muscle contraction can subject healing knee ligament grafts to high loads.

Purpose

To directly measure the effects of quadriceps and hamstrings muscle loads on forces in the anterior cruciate ligaments and posterior cruciate ligaments.

Study Design

Controlled laboratory study.

Methods

Thirteen cadaveric knee specimens had load cells installed to record resultant forces in both anterior and posterior cruciate ligaments under 5 loading conditions. Cruciate force measurements were repeated with a 100-N load applied to the quadriceps tendon and again with a combined 50-N biceps load and 50-N semimembranosus-semitendinosus load.

Results

Applied quadriceps loads resulted in mean changes in anterior cruciate ligament and posterior cruciate ligament forces that were less than 20 N for all loading conditions. Hamstrings load significantly increased mean posterior cruciate ligament force between 30° and 105° of flexion with 100 N of applied posterior tibial force.

Conclusions

At the muscle force levels used in this study, the hamstrings were more effective than the quadriceps in altering cruciate force levels, especially near 90° of flexion, where they have an excellent mechanical advantage for controlling anterior-posterior tibial translation.

Clinical Relevance

Isolated hamstrings activity generally had little or no effect on anterior cruciate ligament forces but significantly increased forces in the posterior cruciate ligament beyond approximately 30° of flexion.
Laparoscopic Repair of Groin Pain in Athletes
Authors: Genitsaris Michael , Goulimaris Ioannis , Sikas Nikolas
Published: May 2004

Background

There has been increasing interest regarding the cause and treatment of groin pain in athletes. The most common finding is a deficiency of the posterior wall of the inguinal canal, often repaired with bilateral inguinal myorrhaphy.

Hypothesis

Laparoscopic repair will offer a shorter convalescent period and better results as compared with open myorrhaphy.

Study Design

Retrospective review of prospectively collected data.

Methods

Between October 1993 and October 2002, 131 athletes with groin pain unrelieved after 2 to 8 months of conservative management underwent bilateral laparoscopic repair with the transabdominal preperitoneal technique for hernias. In 123 (94%) patients, physical examination revealed a dilated external ring, unilateral or bilateral, of the inguinal canal, and in 8 patients (6%) it was normal.

Results

During laparoscopy, a deficiency of the posterior inguinal wall was seen in all athletes. All patients left the hospital 24 hours after the procedure, discontinued oral analgesics within 72 hours of surgery, and were back to full sporting activities with- in 2 to 3 weeks. Four patients (3%) complained of thigh pain. After a mean follow-up of 5 years (range, 4 months to 10 years), there was 1 recurrence (0.76%).

Conclusions

Laparoscopic repair is an efficient method for the treatment of groin pain originating from a deficiency of the posterior inguinal wall, having fast recovery and excellent long-term results.
Histone H1–like protein participates in endothelial cell–specific activation of the von Willebrand factor promoter
Authors: Wang Xinyu , Peng Yiwen , Ma Yuliang , Jahroudi Nadia
Published: May 2004

A region of the von Willebrand factor (VWF) promoter has been identified that is necessary to confer endothelial cell-specific activation to the VWF promoter. This region spans sequences +155 to +247 and contains binding sites for GATA6 and NFY transcription factors. To identify potential DNA binding transcription factors that directly interact with these sequences in an endothelial-specific manner, we have performed extensive gel mobility assays with use of 7 overlapping DNA probes that collectively span this entire region. An endothelial-specific protein DNA complex was formed with an oligonucleotide that corresponded to sequences +155 to +184 of the VWF gene. Mutation analysis identified a 6-nucleotide element corresponding to sequences +164 to +169 as the core-binding region for the formation of this complex. Transfection analysis demonstrated that the mutation, which abolished DNA-protein interaction, resulted in significant inhibition of the VWF promoter activity. DNA pull-down analysis, mass spectrometry, and Western blot analysis demonstrated that a 32-kDa polypeptide with homology to histone H1 constituted the endothelial-specific DNA binding protein, or a DNA binding subunit of this protein complex. On the basis of these results, we hypothesize that an H1-like protein functions as an endothelial cell-specific transcriptional activator of the VWF promoter. (Blood. 2004;104: 1725-1732)
Genomic approaches to hematologic malignancies
Authors: Ebert Benjamin L. , Golub Todd R.
Published: May 2004

In the past several years, experiments using DNA microarrays have contributed to an increasingly refined molecular taxonomy of hematologic malignancies. In addition to the characterization of molecular profiles for known diagnostic classifications, studies have defined patterns of gene expression corresponding to specific molecular abnormalities, oncologic phenotypes, and clinical outcomes. Furthermore, novel subclasses with distinct molecular profiles and clinical behaviors have been identified. In some cases, specific cellular pathways have been highlighted that can be therapeutically targeted. The findings of microarray studies are beginning to enter clinical practice as novel diagnostic tests, and clinical trials are ongoing in which therapeutic agents are being used to target pathways that were identified by gene expression profiling. While the technology of DNA microarrays is becoming well established, genome-wide surveys of gene expression generate large data sets that can easily lead to spurious conclusions. Many challenges remain in the statistical interpretation of gene expression data and the biologic validation of findings. As data accumulate and analyses become more sophisticated, genomic technologies offer the potential to generate increasingly sophisticated insights into the complex molecular circuitry of hematologic malignancies. This review summarizes the current state of discovery and addresses key areas for future research.
OSCAR is an FcRγ-associated receptor that is expressed by myeloid cells and is involved in antigen presentation and activation of human dendritic cells
Authors: Merck Estelle , Gaillard Claude , Gorman Daniel M. , Montero-Julian Felix , Durand Isabelle , Zurawski Sandra M. , Menetrier-Caux Christine , Carra Giuseppe , Lebecque Serge , Trinchieri Giorgio , Bates Elizabeth E. M.
Published: May 2004

We have isolated a novel cell surface molecule, the human homolog of osteoclast-associated receptor (OSCAR). Unlike mouse OSCAR, hOSCAR is widely transcribed in cells of the myeloid lineage. Notably, hOSCAR is expressed on circulating blood monocytes and CD11c+ dendritic cells but not on T and B cells. hOSCAR is continually expressed during differentiation of CD14+ monocytes into dendritic cells and maintained after maturation. hOSCAR associates with the FcRγ as shown by translocation of FcRγ to the cell surface in presence of hOSCAR and coimmunoprecipitation from transfected cell lines and ex vivo cells. Engagement of hOSCAR with specific mAb leads to Ca2+ mobilization and cytokine release, indicators of cellular activation. Endocytosis of the receptor in dendritic cells was observed, followed by passage of the internalized material into Lamp-1+ and HLA-DR+ compartments, suggesting a role in antigen uptake and presentation. Dendritic cells were able to stimulate a T-cell clone specific for an epitope of mouse IgG1 after uptake and processing of the hOSCAR-specific antibody, demonstrating the capacity of this receptor to mediate antigen presentation. hOSCAR thus represents a novel class of molecule expressed by dendritic cells involved in the initiation of the immune response.
Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices
Authors: Shpacovitch V M , Varga G , Strey A , Gunzer M , Mooren F , Buddenkotte J , Vergnolle N , Sommerhoff C P , Grabbe S , Gerke V , Homey B , Hollenberg M , Luger T A , Steinhoff M
Published: May 2004

Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains. PAR2 can be activated by serine proteases such as trypsin, mast cell tryptase, and allergic or bacterial proteases. This receptor is expressed by various cells and seems to be crucially involved during inflammation and the immune response. As previously reported, human neutrophils express functional PAR2. However, the precise physiological role of PAR2 on human neutrophils and its implication in human diseases remain unclear. We demonstrate that PAR2 agonist-stimulated human neutrophils show significantly enhanced migration in 3-D collagen lattices. PAR2 agonist stimulation also induced down-regulation of L-selectin display and up-regulation of membrane-activated complex-1 very late antigen-4 integrin expression on the neutrophil cell surface. Moreover, PAR2 stimulation results in an increased secretion of the cytokines interleukin (IL)-1β, IL-8, and IL-6 by human neutrophils. These data indicate that PAR2 plays an important role in human neutrophil activation and may affect key neutrophil functions by regulating cell motility in the extracellular matrix, selectin shedding, and up-regulation of integrin expression and by stimulating the secretion of inflammatory mediators. Thus, PAR2 may represent a potential therapeutic target for the treatment of diseases involving activated neutrophils.
Immunologic basis for the rare occurrence of true nonsecretory plasma cell dyscrasias
Authors: Decourt Catherine , Galea Horia Radu , Sirac Christophe , Cogné Michel
Published: May 2004

Lymphocytes and plasma cells are major actors of the adaptive immune response and can rightly be considered as human health keepers. However, recombination and mutation events occurring at high rate in the B cell lineage also expose these cells to gene alterations, potentially resulting in uncontrolled and life-threatening cell proliferation. Although in cultured cell lines, such gene alterations frequently generate nonsecretory variants, most immunoproliferative B cell disorders feature in vivo immunoglobulin (Ig) secretion. In this paper, we review the molecular mechanisms involved in various instances of the rare, nonsecretory myelomas, in light of current notions about the molecular control of Ig production, assembly, and secretion in normal B cells. We finallydocument the attractive hypothesis that B cell clones, which retain nonsecretable, intracellular Igs, may be ideal, in vivo targets for efficient anti-idiotypic immune responses, and clones featuring an abundant secretion may by contrast easily induce T cell anergy and escape the anti-tumoral immune surveillance.
Mechanism of Iodide/Chloride Exchange by Pendrin
Authors: Yoshida Akio , Hisatome Ichiro , Taniguchi Shinichi , Sasaki Norihiro , Yamamoto Yasutaka , Miake Junichiro , Fukui Hiroko , Shimizu Hideki , Okamura Tomohisa , Okura Tsuyoshi , Igawa Osamu , Shigemasa Chiaki , Green Eric D. , Kohn Leonard D. , Suzuki Koichi
Published: May 2004

We performed an electrophysiological study to investigate ion transport of pendrin and thereby understand the pathogenesis of Pendred syndrome. Using pendrin-transfected COS-7 cells, we could show that pendrin transports both iodide and chloride measured as voltage-dependent inward and outward membrane currents. Chloride in the culture medium, [Cl−]o, was efficiently exchanged with cytoplasmic iodide, [I−]i, under physiological concentrations, indicating that pendrin is important for chloride uptake and iodide efflux. Although exchange of iodide in the medium, [I−]o, with cytoplasmic chloride, [Cl−]i, was observed, a significantly high concentration of iodide (10 mm) was required. In addition, either iodide or chloride was required on both sides of the cell membrane for the anion exchange activity of pendrin, indicating that iodide and chloride activate the exchange activity of pendrin while they are transported. The present study further supports that pendrin is responsible for the iodide efflux in thyroid cells where intracellular iodide concentration is high and that the general function of pendrin in other tissues is to transport chloride through exchange with other anions.
Convergence of Interferon-γ and Progesterone Signaling Pathways in Human Endometrium: Role of PIASy (Protein Inhibitor of Activated Signal Transducer and Activator of Transcription-y)
Authors: Zoumpoulidou Georgia , Jones Marius C. , de Mattos Silvia Fernandez , Francis Julia M. , Fusi Luca , Lee Yun Soo , Christian Mark , Varshochi Rana , Lam Eric W.-F. , Brosens Jan J.
Published: May 2004

All cardinal events during the reproductive cycle, including ovulation, implantation, and menstruation, are characterized by a profound tissue remodeling and an associated local inflammatory response. The ovarian hormone progesterone is a key modulator of inflammatory signals in reproductive tissues, but the underlying mechanisms are not well understood. In this study, we report that differentiating human endometrial stromal cells (ESCs) acquire resistance to interferon-γ (IFNγ)-dependent signal transducers and activators of transcription (STAT) 1 signaling, although phosphorylation, nuclear translocation, and binding of STAT1 to DNA, are unaffected. These observations prompted an investigation into the role of nuclear repressors of STAT1 signaling. We demonstrate that protein inhibitor of activated STAT-y is complexed to the progesterone receptor (PR) in human ESCs and that its ability to repress STAT1 signaling is dependent upon activation of PR in response to hormone binding. Conversely, IFNγ and protein inhibitor of activated STAT-y synergistically inhibited PR-dependent transcription, demonstrating that the progesterone and IFNγ signaling pathways engage in reciprocal transcriptional antagonism in human endometrium.
Limiting distributions for minimum relative entropy calibration
Authors: Kruk Łukasz
Published: May 2004

We consider minimum relative entropy calibration of a given prior distribution to a finite set of moment constraints. We show that the calibration algorithm is stable (in the Prokhorov metric) under a perturbation of the prior and the calibrated distributions converge in variation to the measure from which the moments have been taken as more constraints are added. These facts are used to explain the limiting properties of the minimum relative entropy Monte Carlo calibration algorithm.
The stochastic precedence ordering with applications in sampling and testing
Authors: Boland Philip J. , Singh Harshinder , Cukic Bojan
Published: May 2004

Stratified and simple random sampling (or testing) are two common methods used to investigate the number or proportion of items in a population with a particular attribute. Although it is known that cost factors and information about the strata in the population are often crucial in deciding whether to use stratified or simple random sampling in a given situation, the stochastic precedence ordering for random variables can also provide the basis for an interesting criteria under which these methods may be compared. It may be particularly relevant when we are trying to find as many special items as possible in a population (for example individuals with a disease in a country). Properties of this total stochastic order on the class of random variables are discussed, and necessary and sufficient conditions are established which allow the comparison of the number of items of interest found in stratified random sampling with the number found in simple random sampling in the stochastic precedence order. These conditions are compared with other results established on stratified and simple random sampling (testing) using different stochastic-order-type criteria, and applications are given for the comparison of sums of Bernoulli random variables and binomial distributions.
Precise large deviations for sums of random variables with consistently varying tails
Authors: Ng Kai W. , Tang Qihe , Yan Jia-An , Yang Hailiang
Published: May 2004

Let {Xk, k ≥ 1} be a sequence of independent, identically distributed nonnegative random variables with common distribution function F and finite expectation μ > 0. Under the assumption that the tail probability is consistently varying as x tends to infinity, this paper investigates precise large deviations for both the partial sums Sn and the random sums SN(t), where N(·) is a counting process independent of the sequence {Xk, k ≥ 1}. The obtained results improve some related classical ones. Applications to a risk model with negatively associated claim occurrences and to a risk model with a doubly stochastic arrival process (extended Cox process) are proposed.
Asymptotic behavior of tail and local probabilities for sums of subexponential random variables
Authors: Ng Kai W. , Tang Qihe
Published: May 2004

Let {Xk,k≥ 1} be a sequence of independently and identically distributed random variables with common subexponential distribution function concentrated on (−∞, ∞), and letτbe a nonnegative and integer-valued random variable with a finite mean and which is independent of the sequence {Xk,k≥ 1}. This paper investigates asymptotic behavior of the tail probabilities P(· >x) and the local probabilities P(x< · ≤x+h) of the quantitiesandforn≥ 1, and their randomized versionsX(τ),SτandS(τ), whereX0= 0 by convention andh> 0 is arbitrarily fixed.
A mosaic of triangular cells formed with sequential splitting rules
Authors: Cowan Richard
Published: May 2004

The iterative division of a triangle by chords which join a randomly-selected vertex of a triangle to the opposite side is investigated. Results on the limiting random graph which eventuates are given. Aspects studied are: the order of vertices; the fragmentation of chords; age distributions for elements of the graph; various topological characterisations of the triangles. Different sampling protocols are explored. Extensive use is made of the theory of branching processes.
Non-Gaussian bifurcating models and quasi-likelihood estimation
Authors: Basawa I. V. , Zhou J.
Published: May 2004

A general class of Markovian non-Gaussian bifurcating models for cell lineage data is presented. Examples include bifurcating autoregression, random coefficient autoregression, bivariate exponential, bivariate gamma, and bivariate Poisson models. Quasi-likelihood estimation for the model parameters and large-sample properties of the estimates are discussed.
Interval and band estimation for curves with jumps
Authors: Gijbels Irène , Hall Peter , Kneip Aloïs
Published: May 2004

Jump points in curves arise when the conditions under which data are generated change suddenly, for example because of an unplanned change in a treatment. This paper suggests bootstrap methods for quantifying the error in estimates of jump points, and for constructing confidence intervals for jump points and confidence bands for the curve. These problems have the unusual feature that the sampling error of the jump-point estimator often has a highly non-normal distribution, which depends intimately on the distribution of regression errors. The methods are illustrated by a simulation study as well as by an application to data on the annual flow volume of the Nile river.
Boundary coiflets for wavelet shrinkage in function estimation
Authors: Johnstone Iain M. , Silverman Bernard W.
Published: May 2004

There are standard modifications of certain compactly supported wavelets that yield orthonormal bases on a bounded interval. We extend one such construction to those wavelets, such as ‘coiflets', that may have fewer vanishing moments than had to be assumed previously. Our motivation lies in function estimation in statistics. We use these boundary-modified coiflets to show that the discrete wavelet transform of finite data from sampled regression models asymptotically provides a close approximation to the wavelet transform of the continuous Gaussian white noise model. In particular, estimation errors in the discrete setting of computational practice need not be essentially larger than those expected in the continuous setting of statistical theory.
Power variation and stochastic volatility: a review and some new results
Authors: Barndorff-Nielsen Ole E. , Graversen Svend Erik , Shephard Neil
Published: May 2004

In this paper we review some recent work on limit results on realised power variation, that is, sums of powers of absolute increments of various semimartingales. A special case of this analysis is realised variance and its probability limit, quadratic variation. Such quantities often appear in financial econometrics in the analysis of volatility. The paper also provides some new results and discusses open issues.
Pricing risk when distributions are fat tailed
Authors: Gay Roger
Published: May 2004

In this paper, insurance claims X on [0, ∞) with tail distributions which are O(x−δ) for some δ > 1 are considered. Markets are assumed arbitrageable, the insurer setting a premium P > E[X]. Setting a premium as a fixed quantile of the loss distribution presents difficulties; for Pareto distributions with F(x) = 1 – (x + l)–δ ‘ultimately' (as δ ↓ 1) E[X] is larger than any quantile. When δ is near 1, premiums determined by weighting outcomes and a rule analogous to the expected utility principle are highly sensitive to change in δ, which is generally unknown or known only approximately. Under these circumstances, to protect insurers' interests, strategies are needed which provide some ‘premium stability' across a range of δ-values. We introduce a class of pricing functions which are functionally dependent on the governing loss distribution, and which are themselves distribution functions. We demonstrate that they provide a coherent framework for pricing insurance premiums when the loss distribution is fat tailed, and enable some degree of premium stability to be established.
On diagnostics in conditionally heteroskedastic time series models under elliptical distributions
Authors: Liu Shuangzhe
Published: May 2004

In statistical diagnostics and sensitivity analysis, the local influence method plays an important rôle. In the present paper, we use this method to study financial time series data and conditionally heteroskedastic models under elliptical distributions. We start with a likelihood displacement, and consider data- and model-perturbation schemes. We obtain corresponding matrices of derivatives, and measures of slope and normal curvature, and then discuss the assessment of local influence.
Maximum dynamic entropy models
Authors: Asadi Majid , Ebrahimi Nader , Hamedani G. G. , Soofi Ehsan S.
Published: May 2004

A formal approach to produce a model for the data-generating distribution based on partial knowledge is the well-known maximum entropy method. In this approach, partial knowledge about the data-generating distribution is formulated in terms of some information constraints and the model is obtained by maximizing the Shannon entropy under these constraints. Frequently, in reliability analysis the problem of interest is the lifetime beyond an age t. In such cases, the distribution of interest for computing uncertainty and information is the residual distribution. The information functions involving a residual life distribution depend on t, and hence are dynamic. The maximum dynamic entropy (MDE) model is the distribution with the density that maximizes the dynamic entropy for all t. We provide a result that relates the orderings of dynamic entropy and the hazard function for distributions with monotone densities. Applications include dynamic entropy ordering within some parametric families of distributions, orderings of distributions of lifetimes of systems and their components connected in series and parallel, record values, and formulation of constraints for the MDE model in terms of the evolution paths of the hazard function and mean residual lifetime function. In particular, we identify classes of distributions in which some well-known distributions, including the mixture of two exponential distributions and the mixture of two Pareto distributions, are the MDE models.
Optimal stopping rules for correlated random walks with a discount
Authors: Allaart Pieter
Published: May 2004

Optimal stopping rules are developed for the correlated random walk when future returns are discounted by a constant factor per unit time. The optimal rule is shown to be of dual threshold form: one threshold for stopping after an up-step, and another for stopping after a down-step. Precise expressions for the thresholds are given for both the positively and the negatively correlated cases. The optimal rule is illustrated by several numerical examples.
A finite-time ruin probability formula for continuous claim severities
Authors: Ignatov Zvetan G. , Kaishev Vladimir K.
Published: May 2004

An explicit formula for the probability of nonruin of an insurance company in a finite time interval is derived, assuming Poisson claim arrivals, any continuous joint distribution of the claim amounts and any nonnegative, increasing real function representing its premium income. The formula is compact and expresses the nonruin probability in terms of Appell polynomials. An example, illustrating its numerical convenience, is also given in the case of inverted Dirichlet-distributed claims and a linearly increasing premium-income function.
Note on Zeifman's bounds on the rate of convergence for birth-death processes
Authors: Mitrophanov A. Yu.
Published: May 2004

It is shown that the method of deriving bounds on the rate of convergence for birth–death processes developed by Zeifman can be effectively applied to stochastic models of chemical reactions.
The teaching of statistical consulting
Authors: Russell K. G.
Published: May 2004

This paper considers how students might be taught statistical consulting. Desirable characteristics of a good consultant are described. While skill in statistical techniques is considered, it is just one of several areas of expertise that are discussed. Suggestions are made as to what should be included in a consulting course to equip a student with these characteristics.
Priority queueing model with changeover times and switching threshold
Authors: Deng Yonglu , Tan Jiqing
Published: May 2004

The paper studies a single-server two-queue priority system with changeover times and switching threshold. The server serves queue 1 exhaustively and does not remain at an empty queue if the other one is non-empty. It immediately switches from queue 2 to queue 1 when the length of the latter reaches some level M. Whenever service is changed from one queue to the other a changeover time is required. Arrivals are Poisson, service times and changeover times are independent and exponentially distributed. Using an analytic method we obtain the steady-state joint probability generating function of the lengths of the two queues. By means of this probability generating function some performance measures of the system such as mean length of queue and mean delay can be calculated.
Single cell lineage and regionalization of cell populations during Medaka neurulation
Authors: Hirose Yukihiro , Varga Zoltan M. , Kondoh Hisato , Furutani-Seiki Makoto
Published: May 2004

To study the movement of individual cells and development of cell grouping during neurogenesis, we labeled single cells in early Medaka gastrula at stage 13 [13 hours post-fertilization (hpf)] with a fluorescent vital dye, and analyzed cells and their descendants using time-lapse live recording up to stage 24 (44 hpf). At stage 13, all future neural cells were located in a dorsal 140° sector of the embryo, and migrated toward the vegetal pole;but during stage 15 to 16, they converged towards the midline. Cells that contributed to later neural subdivisions initially formed overlapping populations, but after stage 16+ they formed non-overlapping cell groups having characteristics of tissue `compartments', preceding development of morphologically distinct neural subdivisions. In early retinal development, a single compartment for future retinal cells was formed superficial to telencephalic and diencephalic compartments, but it was split into left and right eye components at stage 17 in parallel with anterodorsal movement of the diencephalic compartment. At stage 16+, when these compartments were established, Pax6 expression initiated, but only in the laterally located subpopulation of the retina precursor. These observations revise the current view of bilateral retinal development. Continuous live recording of labeled single precursor cells and computer graphics-assisted data analysis,which are presented for the first time in this study, provide excellent means with which to analyze essential cellular processes in organogenesis.
TheDrosophilaARF6-GEF Schizo controls commissure formation by regulating Slit
Authors: Önel Susanne , Bolke Liane , Klämbt Christian
Published: May 2004

The CNS of bilateral symmetric organisms is characterized by intensive contralateral axonal connections. Genetic screens in Drosophila have identified only a few genes required for guiding commissural growth cones toward and across the midline. Two evolutionarily conserved signaling molecules, Netrin and Slit, are expressed in the CNS midline cells. Netrin acts primarily as an attractive signaling cue, whereas Slit mediates repulsive functions. Here, we describe a detailed analysis of the Drosophilagene schizo, which is required for commissure formation. schizo leads to a commissural phenotype reminiscent of netrin mutant embryos. Double-mutant analyses indicate that Netrin and Schizo act independently. The schizo mutant phenotype can be suppressed by either expressing netrin in the CNS midline cells or by a reduction of the slit gene dose, indicating that the balance of attractive and repulsive signaling is impaired in schizo mutants. Overexpression of the schizo RNA in the CNS midline using the GAL4/UAS system leads to a slit phenocopy, suggesting that schizo primarily antagonizes Slit signaling. This is further supported by cell type-specific rescue experiments. The schizo gene generates at least two proteins containing a conserved Sec7 and a pleckstrin homology domain (PH) characteristic for guanine nucleotide exchange factors(GEF) acting on ARF GTPases, which are known to regulate endocytosis.In support of the notion that schizo regulates Slit expression via endocytosis, we found that block of endocytosis leads to a schizo-like phenotype. We thus propose that the balance of the two signaling cues Netrin and Slit can be regulated, controlling membrane dynamics.
Fgf signalling controls the dorsoventral patterning of the zebrafish embryo
Authors: Fürthauer Maximilian , Van Celst Jeanne , Thisse Christine , Thisse Bernard
Published: May 2004

The establishment of dorsoventral (DV) patterning in vertebrate embryos depends on the morphogenic activity of a group of Tgfβ superfamily members, the bone morphogenetic proteins (Bmps) (which specify ventral cell fates), and on their interaction with their dorsally secreted cognate inhibitors chordin and noggin. In the zebrafish, genetic analysis has revealed that Bmp2b and Bmp7, as well as their antagonist chordin, are required for proper DV patterning. The expression of Bmp genes is initially activated in the whole blastula. Well before the beginning of gastrulation, Bmp gene expression progressively disappears from the dorsal side to become restricted to the ventral part of the embryo. We show that this early restriction of Bmp gene expression, which occurs independently of noggin and chordin, is an essential step in the establishment of DV patterning. The progressive ventral restriction of Bmp gene transcripts is coincident with the spreading of Fgf activity from the dorsal side of the embryo, suggesting that Fgf signalling is implicated in dorsal downregulation of Bmp gene expression. In accordance with this, activation of the Fgf/Ras/Mapk-signalling pathway inhibits ventral Bmp gene expression, thereby causing a dorsalisation of the embryo. Conversely,inhibition of Fgf signalling causes Bmp gene expression to expand dorsally,leading to an expansion of ventral cell fates. In accordance with an important role of Fgf signalling in the DV patterning of the zebrafish, we show that loss of Fgf8 function enhances the ventralisation of chordin-deficient embryos. Our results thereby demonstrate that pre-gastrula stage Fgf-signalling is essential to delimit the expression domain of the genes encoding the functional morphogen of the dorsoventral axis of the early zebrafish embryo.