bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural changes in dysferlinopathy support defective membrane repair mechanism
Authors: Cenacchi G , Fanin M , De Giorgi L B , Angelini C
Published: January 2005

Background:The dysferlin gene has recently been shown to be involved in limb girdle muscular dystrophy type 2B and its allelic disease, Miyoshi myopathy, both of which are characterised by an active muscle degeneration and regeneration process. Dysferlin is known to play an essential role in skeletal muscle fibre repair, but the process underlying the pathogenetic mechanism of dysferlinopathy is not completely understood.

Aims:To define both specific alterations of muscle fibres and a possible sequential mechanism of myopathy development.

Methods:A histological, immunohistochemical, and ultrastructural analysis of 10 muscle biopsies from patients with molecularly diagnosed dysferlinopathy.

Results:An inflammatory response was seen in most of the muscle biopsies. The immunohistochemical pattern demonstrated active regeneration and inflammation. Non-necrotic fibres showed alterations at different submicroscopic levels, namely: the sarcolemma and basal lamina, subsarcolemmal region, and sarcoplasmic compartment. In the subsarcolemmal region there were prominent aggregations of small vesicles, probably derived from the Golgi apparatus, which consisted of empty, swollen cisternae. In the sarcolemma there were many gaps and microvilli-like projections, whereas the basal lamina was multilayered.

Conclusions:The histopathological, immunohistochemical, and ultrastructural data show that dysferlinopathy is characterised by a very active inflammatory/degenerative process, possibly associated with an inefficient repair and regenerative system. The presence of many crowded vesicles just beneath the sarcolemma provides submicroscopical proof of a defective resealing mechanism, which fails to repair the sarcolemma.
LYVE-1 immunohistochemical assessment of lymphangiogenesis in endometrial and lung cancer: Figure 1
Authors: Koukourakis M I , Giatromanolaki A , Sivridis E , Simopoulos C , Gatter K C , Harris A L , Jackson D G
Published: January 2005

Aims/Methods:Normal and malignant pulmonary and endometrial tissues were analysed for lymphatic vessels to assess the process of lymphangiogenesis and its role at these sites, using specific immunostaining for LYVE-1 and the panendothelial marker CD31.

Results:Lymphatics were clearly demonstrated in some normal tissues (myometrium, bronchial submucosa, and intestinal submucosa), but not in others (endometrium and alveolar tissue). LYVE-1 positive lymphatic vessels were detected at the tumour periphery of endometrial and lung carcinomas, but not within the main tumour mass. Double staining for LYVE-1 and the MIB1 proliferation marker revealed a higher proliferation index in lymphatic endothelial cells at the invading front of endometrial carcinomas, compared with myometrial areas distal to the tumour. Lung and endometrial carcinomas did not have an intratumorous lymphatic network.

Conclusions:Although lymphangiogenesis may occur at the invading tumour front, incorporated lymphatics do not survive. Therefore, the dissemination of cancer cells through the lymphatics may occur by invasion of peripheral cancer cells into the adjacent normal lymphatics, or through shunts eventually produced at the invading tumour front as a consequence of active angiogenesis and lymphangiogenesis.
Alterations of mononuclear inflammatory cells, CD4/CD8+ T cells, interleukin 1β, and tumour necrosis factor α in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis
Authors: Hussein M R , Hassan H I , Hofny E R M , Elkholy M , Fatehy N A , Abd Elmoniem A E A , Ezz El-Din A M , Afifi O A , Rashed H G
Published: January 2005

Background:Systemic sclerosis (SSc) is a multisystem disease with underlying immune mechanisms.

Aims:To investigate the clinicopathological characteristics of the lesions; immunological alterations in the bronchoalveolar lavage fluid (BALF), peripheral blood, and skin; and correlations between the clinicopathological characteristics and immunological alterations in SSc.

Materials/Methods:Skin biopsies, BALF, and peripheral blood samples were obtained from 19 patients (18 women, one man) with SSc and six age and sex matched healthy controls (HCs). Mononuclear inflammatory cells (MICs), CD4/CD8 cells, tumour necrosis factor α (TNFα), and interleukin 1β (IL1-1β) concentrations were examined in all samples using histological methods, enzyme linked immunosorbent assay, and immunoperoxidase staining.

Results:The mean (SD) age of the patients with SSc was 34.8 (2.6) years. Proteinuria, positive rheumatoid factor, and C reactive protein were seen in 15.8%, 26.3%, and 26.3% of patients, respectively. Compared with HCs, there were significantly higher: total MICs (macrophages, lymphocytes), neutrophils, and eosinophils in BALF, blood, and skin (all p<0.05); cytokine concentrations in BALF (TNFα, p<0.001; IL-1, p<0.01) and peripheral blood (p<0.01 and p<0.05); and CD8/CD4+ T cells in peripheral blood (p<0.05). Compared with HCs, lesional skin had significantly higher histiocyte cell counts (p<0.05), lower lymphocyte counts (p<0.05), and higher CD4/CD8 ratios (p<0.001). There were significant correlations between cytokine concentrations and CD8+ T cells and forced vital capacity (p<0.001 and p<0.01, respectively).

Conclusions:MICs, CD4/CD8+ cells, and cytokines are altered in SSc. These alterations correlated with the underlying disease process and therefore may have pathogenic, modulatory, and potential prognostic roles in SSc.
Best Practice No 181: Table 1
Authors: Reynolds T M
Published: January 2005

Renal stones have afflicted humans for millennia but there is still no solution to this problem. This review discusses the laboratory and metabolic aspects of the clinical management of patients with renal stones, both primary and secondary in origin. First, non-pharmacological interventions such as increased fluid intake, decreased protein consumption, dietary changes in sodium, calcium, oxalate, potassium, purine, vitamins, and essential fatty acids are considered. Then specific pharmacological treatment to modify urine calcium, oxalate, urate, citrate, and acidity are considered. Finally, more unusual types of stone are examined.
Extramedullary myeloid tumour (EMMT) of the gallbladder
Authors: Ojima H , Hasegawa T , Matsuno Y , Sakamoto M
Published: January 2005

This report describes a rare case of an extramedullary myeloid tumour (EMMT) of the gallbladder in a patient without leukaemia. A 33 year old man visited a local hospital because of jaundice. Abdominal computed tomography revealed a tumorous mass measuring 6.0 × 4.5 cm and involving the entire gallbladder. A percutaneous needle biopsy was attempted, but because adenocarcinoma could not be completely ruled out, the use of undue force was considered dangerous. Under a preoperative diagnosis of gallbladder carcinoma, a hepatopancreatoduodenectomy was performed. The tumour cells exhibited various amounts of eosinophilic cytoplasm, had medium sized round nuclei with indentation and grooving, and were strongly immunoreactive for myeloperoxidase, CD43, and c-kit protein (CD117). After surgery, the patient underwent combination chemotherapy as prescribed for cases of acute myeloblastic leukaemia. The patient did not develop acute leukaemia during a follow up period of four years. In conclusion, a correct diagnosis of EMMT can be made using appropriate immunohistochemical staining.
Differential prognostic impact of hypoxia induced and diffuse HIF-1α expression in invasive breast cancer
Authors: Vleugel M M , Greijer A E , Shvarts A , van der Groep P , van Berkel M , Aarbodem Y , van Tinteren H , Harris A L , van Diest P J , van der Wall E
Published: January 2005

Background:Intratumorous hypoxia triggers a broad cellular response mediated by the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1α concentrations increase during breast carcinogenesis, and are associated with poor prognosis. An earlier study noted two HIF-1α overexpression patterns: diffuse scattered throughout the tissue and confined to perinecrotic cells.

Aims:To investigate the prognostic impact of these different HIF-1α overexpression patterns in relation to its downstream effectors carbonic anhydrase (CA) IX and glucose transporter 1 (GLUT-1).

Methods:HIF-1α, CA IX, and GLUT-1 expression was studied by immunohistochemistry, including double staining for CA IX and HIF-1α. Clinical data included disease free survival, lymph node status, and tumour size.

Results:HIF-1α overexpression (44% of cases) had a perinecrotic (13.5%) or diffuse staining pattern (30.5%). CA IX expression was detectable in 12.5% of breast cancers, whereas GLUT-1 expression was seen in 29%, with both showing perinecrotic membrane staining. Perinecrotic HIF-1α overexpression was highly associated with CA IX and GLUT-1 overexpression, and double staining for HIF-1α and CA IX showed strong expression in the same cells. Diffusely overexpressed HIF-1α was not associated with CA IX or GLUT-1 expression. Patients with diffuse HIF-1α staining had a significantly better prognosis than patients with perinecrotically overexpressed HIF-1α.

Conclusions:Different regulation pathways of HIF-1α overexpression exist in breast cancer: (1) hypoxia induced, perinecrotic HIF-1α overexpression with strong expression of hypoxia associated genes (CA IX and GLUT-1), which is associated with a poor prognosis; and (2) diffuse HIF-1α overexpression lacking major hypoxia associated downstream effects, resulting in a more favourable prognosis.
Analysis of prosthetic cardiac devices: a guide for the practising pathologist
Authors: Butany J , Collins M J
Published: January 2005

Pathologists all over the world increasingly encounter prosthetic cardiac devices. A good evaluation of these devices is a valuable source of information, which can contribute to patient care and the appreciation and understanding of the pathobiology involved in the changes occurring between the host and the implanted prosthetic device. This article summarises the considerations underlying the analysis of prosthetic devices (particularly prosthetic heart valves), including the identification of the devices, the major morphological features of the devices, their modes of failure, and some technical details about evaluation and pitfalls.
Osseous metaplasia in a tubular adenoma of the colon: Figure 1
Authors: Al-Daraji W I , Abdellaoui A , Salman W D
Published: January 2005

An 85 year old woman presented with a one month history of change in her bowel habits in the form of alternating diarrhoea and constipation. She also noted some rectal bleeding. Flexible sigmoidoscopy revealed a 1.5 cm polyp 30 cm from the anus. The polyp was removed during the sigmoidoscopy by electrocautery and sent for histological examination. The polyp was a tubular adenoma with mild dysplasia. The adenoma contained numerous foci of metaplastic bone. These consisted of irregular islands of mineralised osteoid bone rimmed by a layer of scattered osteoblasts. This is the first case of osseous metaplasia in a tubular adenoma of the colon to be reported.
Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours
Authors: Tse G M K , Tsang A K H , Putti T C , Scolyer R A , Lui P C W , Law B K B , Karim R Z , Lee C S
Published: January 2005

Background/Aims:CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions.

Methods:Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy.

Results:There was a progressive increase in the patients’ age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours.

Conclusions:CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.
A methylation sensitive dot blot assay (MS-DBA) for the quantitative analysis of DNA methylation in clinical samples
Authors: Clément G , Benhattar J
Published: January 2005

Background:There is increasing interest in DNA methylation and in its implication in transcriptional gene silencing, a phenomenon commonly seen in human cancer.

Aims:To develop a new method that would allow quantitative DNA methylation analysis in a large range of clinical samples, independently of the processing protocol.

Methods:A methylation sensitive dot blot assay (MS-DBA) was developed, which is quantitative and combines bisulfite modification, PCR amplification using primers without CpG sites, and dot blot analysis with two probes specific for methylated and unmethylated DNA.

Results:The established method was used to study methylation of the hTERT, APC, and p16 promoter regions in microdissected, formalin fixed and paraffin wax embedded tissues.

Conclusions:MS-DBA is a sensitive, specific, and quantitative approach to analyse DNA methylation in a variety of frozen or fixed tissues. Moreover, MS-DBA is rapid, easy to perform, and permits the screening of a large panel of samples in one experiment. Thus, MS-DBA can facilitate the routine analysis of DNA methylation in all types of clinical samples.
Effects of sarcoplasmic reticulum Ca2+-ATPase overexpression in postinfarction rat myocytes
Authors: Ahlers Belinda A. , Song Jianliang , Wang JuFang , Zhang Xue-Qian , Carl Lois L. , Tadros George M. , Rothblum Lawrence I. , Cheung Joseph Y.
Published: January 2005

Previous studies in adult myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) demonstrated abnormal contractility and intracellular Ca2+ concentration ([Ca2+]i) homeostasis and decreased sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expression and activity, but sarcoplasmic reticulum Ca2+ leak was unchanged. In the present study, we investigated whether SERCA2 overexpression in MI myocytes would restore contraction and [Ca2+]i transients to normal. Compared with sham-operated hearts, 3-wk MI hearts exhibited significantly higher left ventricular end-diastolic and end-systolic volumes but lower fractional shortening and ejection fraction, as measured by M-mode echocardiography. Seventy-two hours after adenovirus-mediated gene transfer, SERCA2 overexpression in 3-wk MI myocytes did not affect Na+-Ca2+ exchanger expression but restored the depressed SERCA2 levels toward those measured in sham myocytes. In addition, the reduced sarcoplasmic reticulum Ca2+ uptake in MI myocytes was improved to normal levels by SERCA2 overexpression. At extracellular Ca2+ concentration of 5 mM, the subnormal contraction and [Ca2+]i transient amplitudes in MI myocytes (compared with sham myocytes) were restored to normal by SERCA2 overexpression. However, at 0.6 mM extracellular Ca2+ concentration, the supernormal contraction and [Ca2+]i transient amplitudes in MI myocytes (compared with sham myocytes) were exacerbated by SERCA2 overexpression. We conclude that SERCA2 overexpression was only partially effective in ameliorating contraction and [Ca2+]i transient abnormalities in our rat model of ischemic cardiomyopathy. We suggest that other Ca2+ transport pathways, e.g., Na+-Ca2+ exchanger, may also play an important role in contractile and [Ca2+]i homeostatic abnormalities in MI myocytes.
Expression of Ankrd2 in fast and slow muscles and its response to stretch are consistent with a role in slow muscle function
Authors: Mckoy G. , Hou Y. , Yang S. Y. , Vega Avelaira D. , Degens H. , Goldspink G. , Coulton G. R.
Published: January 2005

In striated muscle, the structural genes associated with muscle fiber phenotype determination as well as muscle mass accretion are regulated largely by mechanical stimuli. Passive stretch of skeletal muscle stimulates muscle growth/hypertrophy and an increased expression of slow muscle genes. We previously identified Ankyrin repeat-domain protein ( Ankrd2) as a novel transcript expressed in fast tibialis anterior muscles after 7 days of passive stretch immobilization in vivo. Here, we test the hypothesis that the expression of Ankrd2 in stretched fast muscle is associated with the stretch-induced expression of slow muscle phenotype rather than the hypertrophic response. Our results show that, in 4- and 7-day stretched tibialis anterior muscle, the expression of Ankrd2 mRNA and protein was significantly upregulated ( P > 0.001). However, in fast muscles of kyphoscoliotic mutant mice, which lack the hypertrophic response to overload but have a slower muscle phenotype than wild-type, Ankrd2 expression was significantly upregulated. The distribution pattern of Ankrd2 in fast and slow muscle is also in accord with their slow fiber composition. Furthermore, it was markedly downregulated in denervated rat soleus muscle, which produces a pronounced shift toward the fast muscle phenotype. Using a sensitive proteomics approach (Ciphergen Technology), we observed that Ankrd2 protein was undetectable in soleus after 4 wk of denervation. We suggest that Ankrd2, which is also a titin binding protein, is a stretch-response gene associated with slow muscle function and that it is part of a separate mechanotransduction system to the one that regulates muscle mass.
High-frequency, low-magnitude vibrations suppress the number of blood vessels per muscle fiber in mouse soleus muscle
Authors: Murfee Walter L. , Hammett Laura A. , Evans Caroline , Xie Liqin , Squire Maria , Rubin Clinton , Judex Stefan , Skalak Thomas C.
Published: January 2005

Extremely low-magnitude (0.3 g), high-frequency (30–90 Hz), whole body vibrations can stimulate bone formation and are hypothesized to provide a surrogate for the oscillations of muscle during contraction. Little is known, however, about the potential of these mechanical signals to stimulate adaptive responses in other tissues. The objective of this study was to determine whether low-level mechanical signals produce structural adaptations in the vasculature of skeletal muscle. Eight-week-old male BALB/cByJ (BALB) mice were divided into two experimental groups: mice subjected to low-level, whole body vibrations (45 Hz, 0.3 g) superimposed on normal cage activities for 15 min/day ( n = 6), and age-matched controls ( n = 7). After the 6-wk experimental protocol, sections from end and mid regions of the soleus muscles were stained with lectin from Bandeiraea Simplicifolia, an endothelial cell marker, and smooth muscle (SM) α-actin, a perivascular cell marker. Six weeks of this low-level vibration caused a 29% decrease in the number of lectin-positive vessels per muscle fiber in the end region of the soleus muscle, indicating a significant reduction in the number of capillaries per muscle fibers. Similarly, these vibrations caused a 36% reduction in SM α-actin-positive vessels per muscle fiber, indicating a reduction in the number of arterioles and venules. The decreases in lectin- and SM α-actin-positive vessels per muscle fiber ratios were not significant in the mid muscle sections. These results demonstrate the sensitivity of the vasculature in mouse skeletal muscle to whole body, low-level mechanical signals.
Functional imaging of working memory in obstructive sleep-disordered breathing
Authors: Thomas Robert J. , Rosen Bruce R. , Stern Chantal E. , Weiss J. Woodrow , Kwong Kenneth K.
Published: January 2005

Functional magnetic resonance imaging was used to map cerebral activation in 16 patients with obstructive sleep-disordered breathing (OSDB) and 16 healthy subjects, during the performance of a 2-back verbal working memory task. Six patients with OSDB were reimaged after a minimum period of 8 wk of treatment with positive airway pressure. Working memory speed in OSDB was significantly slower than in healthy subjects, and a group average map showed absence of dorsolateral prefrontal activation, regardless of nocturnal hypoxia. After treatment, resolution of subjective sleepiness contrasted with no significant change in behavioral performance, persistent lack of prefrontal activation, and partial recovery of posterior parietal activation. These findings suggest that working memory may be impaired in OSDB and that this impairment is associated with disproportionate impairment of function in the dorsolateral prefrontal cortex. Nocturnal hypoxia may not be a necessary determinant of cognitive dysfunction, and sleep fragmentation may be sufficient. There may be dissociations between respiratory vs. cortical recovery and objective vs. subjective recovery. Hypofrontality may provide a plausible biological mechanism for a clinical overlap with disorders of mood and attention.
Robustly stable multiestimation scheme for adaptive control andidentification with model reduction issues
Authors: Bilbao-Guillerna A. , De La Sen M. , Ibeas A. , Alonso-Quesada S.
Published: January 2005

A discrete pole‐placement‐based and multiestimation‐based
adaptive control scheme involving a relative adaptation dead zone is presented for a plant with known poles and unknown zeros. The basic usefulness of the proposed multiestimation scheme is related to the use of a set of models of reduced order associated
with the multiestimation scheme instead of a high‐order one. Depending on the frequency spectrum characteristics of the input and on the estimates evolution, the multiestimation scheme selects on‐line the most appropriate model and its related estimation scheme in order to improve the identification and control performances. Robust closed‐loop stability is proved even in the presence of unmodeled dynamics of sufficiently small sizes as it has been confirmed by simulation results. The scheme chooses in real time the estimator/controller associated with a particular reduced model possessing the best performance according to an identification performance index by implementing a switching rule between estimators. The switching rule is subject to a minimum residence time at each identifier/adaptive controller parameterization for closed‐loop stabilization purposes. A conceptually simple higher‐level supervisor, based on heuristic updating rules which estimate on‐line the weights of the switching rule between estimation schemes, is discussed.
Irreducible complexity of iterated symmetric bimodal maps
Authors: Lampreia J. P. , Severino R. , Ramos J. Sousa
Published: January 2005

We introduce a tree structure for the iterates of symmetric bimodal maps and identify a subset which we prove to be isomorphic to the family of unimodal maps. This subset is used as a second factor for a ∗‐product that we define in the space of bimodal kneading sequences. Finally, we give some properties for this product and study the ∗‐product induced on the associated Markov shifts.
A simple mathematical model for Batesian mimicry
Authors: Blows Terence R. , Wimmer Barry J.
Published: January 2005

A simple mathematical model is presented for Batesian mimicry,
which occurs when a harmless species (mimic) is morphologically similar to another species (model) that is noxious or distasteful to predators, thus gaining a measure of protection. Although mathematical models for species interaction, such as predator‐prey
or competition, are well known, there is no similar literature on mimicry. The mathematical model developed here is a one‐dimensional iterated map which has the full range of dynamic behavior present in the logistic map, depending on the values of its parameters. The dynamics ranges from a stable fixed point and stable cycles through chaotic dynamics achieved through a sequence of period doubling bifurcations.
Rothe time‐discretization method for a nonlocal problem arising in thermoelasticity
Authors: Merazga Nabil , Bouziani Abdelfatah
Published: January 2005

We investigate a model parabolic mixed problem with purely boundary integral conditions arising in the context of thermoelasticity. Using the Rothe method which is based on a semidiscretization of the given problem with respect to the time variable, the questions of existence, uniqueness, and continuous dependence upon data of a weak solution are proved. Moreover, we establish convergence and derive an error estimate for a semidiscrete approximation.
On the asymptotic behavior of solutions of certain third‐order nonlinear differential equations
Authors: Tunç Cemil
Published: January 2005

We establish sufficient conditions under which all solutions of the third‐order nonlinear differential equation are bounded and converge to zero as t → ∞.
Tauberian theorems for summability transforms
Authors: Goonatilake Rohitha
Published: January 2005

The convolution summability method is introduced as a generalization of the random‐walk method. In this paper, two well‐known summability analogs concerning the strong law of large numbers (SLLN) and the law of the single logarithm (LSL), that gives the rate of convergence in SLLN for the random‐walk method, are extended to this generalized method.
Maximum process problems in optimal control theory
Authors: Peskir Goran
Published: January 2005

Given a standard Brownian motion and the equation of motion , we set St = max0≤s≤tXs and consider the optimal control problem supvE(Sτ − Cτ), where c > 0 and the supremum is taken over all admissible controls v satisfying vt ∈ [μ0, μ1] for all t up to τ = inf{t > 0|Xt ∉ (ℓ0, ℓ1)} with μ0 < 0 < μ1 and ℓ0 < 0 < ℓ1 given and fixed. The following control v∗ is proved to be optimal: “pull as hard as possible,” that is, if Xt < g∗(St), and “push as hard as possible,” that is, if Xt > g∗(St), where s ↦ g∗(s) is a switching curve that is determined explicitly (as the unique solution to a nonlinear differential equation). The solution found demonstrates that the problem formulations based on a maximum functional can be successfully included in optimal control theory (calculus of variations) in addition to the classic problem formulations due to Lagrange, Mayer, and Bolza.
Reliability for some bivariate beta distributions
Authors: Nadarajah Saralees
Published: January 2005

In the area of stress‐strength models there has been a large
amount of work as regards estimation of the reliability R = Pr(X < Y). The algebraic form for R = Pr(X < Y) has been worked out for the vast majority of the well‐known distributions when X and Y are independent random variables belonging to the same
univariate family. In this paper, we consider forms of R when (X, Y) follows a bivariate distribution with dependence between
X and Y. In particular, we derive explicit expressions for R when the joint distribution is bivariate beta. The calculations
involve the use of special functions.
Solution of nonlinear Fredholm‐Hammerstein integral equations by using semiorthogonal spline wavelets
Authors: Lakestani M. , Razzaghi M. , Dehghan M.
Published: January 2005

Compactly supported linear semiorthogonal B‐spline wavelets
together with their dual wavelets are developed to approximate the solutions of nonlinear Fredholm‐Hammerstein integral equations. Properties of these wavelets are first presented; these properties are then utilized to reduce the computation of integral equations
to some algebraic equations. The method is computationally attractive, and applications are demonstrated through an illustrative example.
A decomposition‐based control strategy for large, sparse dynamic systems
Authors: Zečević Aleksandar I. , Šiljak Dragoslav D.
Published: January 2005

We propose a new output control design for large, sparse dynamic
systems. A graph‐theoretic decomposition is used to cluster the states, inputs, and outputs,
and to identify an appropriate bordered block diagonal structure for the gain matrix. The resulting control law can be easily implemented in a multiprocessor environment with a minimum of communication. A large‐scale problem is considered to demonstrate the validity of the proposed approach.
On the numerical solution of the one‐dimensional convection‐diffusion equation
Authors: Dehghan Mehdi
Published: January 2005

The numerical solution of convection‐diffusion transport problems
arises in many important applications in science and engineering. These problems occur in many applications such as in the transport of air and ground water pollutants, oil reservoir flow, in the modeling of semiconductors, and so forth. This paper describes
several finite difference schemes for solving the one‐dimensional convection‐diffusion equation with constant coefficients. In this research the use of modified equivalent partial differential equation (MEPDE) as a means of estimating the order of accuracy of a given finite difference technique is emphasized. This approach can unify the deduction of arbitrary techniques for the numerical solution of convection‐diffusion equation. It is
also used to develop new methods of high accuracy. This approach allows simple comparison of the errors associated with the partial differential equation. Various difference approximations are derived for the one‐dimensional constant coefficient convection‐diffusion equation. The results of a numerical experiment are provided, to verify the efficiency of the designed new algorithms. The paper ends with a concluding remark.
Long‐run availability of a priority system: a numerical approach
Authors: Vanderperre Edmond J. , Makhanov Stanislav S.
Published: January 2005

We consider a two‐unit cold standby system attended by two
repairmen and subjected to a priority rule. In order to describe the random behavior of the twin system, we employ a stochastic process endowed with state probability functions satisfying coupled Hokstad‐type differential equations. An explicit evaluation of the exact solution is in general quite intricate. Therefore, we propose a numerical solution of the equations. Finally, particular but important repair time distributions are involved to analyze the long‐run availability of the T‐system. Numerical results are illustrated by adequate computer‐plotted graphs.
Similarity to contraction and asymptotics of a class of infinite‐dimensional discrete‐time systems
Authors: Yamé Joseph J.
Published: January 2005

A class of infinite‐dimensional discrete‐time state operators is
exhibited as concrete instances of power‐bounded operators that are not similar to contractions. It is shown that such discrete‐time systems arise from sampled feedback control of unstable continuous‐time systems. The asymptotic behavior of the state operators of these discrete systems is not intimately related to their spectral radius.
Quantification of Isoprostanes as Indices of Oxidant Stress and the Risk of Atherosclerosis in Humans
Authors: Morrow Jason D.
Published: January 2005

Enhanced oxidant stress occurring either locally in the vessel wall or systemically is implicated in the pathogenesis of atherosclerosis in humans. Nonetheless, evidence that oxidant stress is increased in vivo in association with this disease and that it can be quantified in living human beings has been lacking because of the unavailability of biomarkers to assess oxidant stress in humans. Recently, the development of methods to quantify the F
2
-isoprostanes (IsoPs), prostaglandin (PG)-like compounds derived from the free radical-catalyzed peroxidation of arachidonic acid, has allowed, for the first time to the author’s knowledge, a facile and accurate assessment of oxidant stress in vivo. The purpose of this brief review is to discuss the usefulness of quantifying IsoPs as an index of oxidative injury in association with atherosclerosis. F
2
-IsoPs can be measured in human biological fluids, such as plasma and urine, using highly precise assays. They have been shown to be increased in association in with a number of atherosclerotic risk factors, including cigarette smoking, hypercholesterolemia, diabetes mellitus, and obesity, among others. In addition, recent evidence suggests their quantification may represent an independent marker of atherosclerotic risk. A reduction in cardiovascular risk factors is associated with a decrease in IsoP formation in humans. Despite the fact that the role of oxidant stress in the pathogenesis of atherosclerosis is a hotly debated issue, current evidence suggests that the IsoPs represent a biomarker that has the potential to be of great importance in the assessment of human atherosclerotic cardiovascular disease.
c-Src and Hydrogen Peroxide Mediate Transforming Growth Factor-β1–Induced Smooth Muscle Cell–Gene Expression in 10T1/2 Cells
Authors: Sato Mahito , Kawai-Kowase Keiko , Sato Hiroko , Oyama Yuko , Kanai Hiroyoshi , Ohyama Yoshio , Suga Tatsuo , Maeno Toshitaka , Aoki Yasuhiro , Tamura Junichi , Sakamoto Hironosuke , Nagai Ryozo , Kurabayashi Masahiko
Published: January 2005

Objective—

Transforming growth factor-β1 (TGF-β1) controls the expression of numerous genes, including smooth muscle cell (SMC)–specific genes and extracellular matrix protein genes. Here we investigated whether c-Src plays a role in TGF-β1 signaling in mouse embryonic fibroblast C3H10T1/2 cells.

Methods and Results—

TGF-β1 induction of the SMC contractile protein SM22α gene expression was inhibited by PP1 (an inhibitor of Src family kinases) or by C-terminal Src kinase (a negative regulator of c-Src). Induction of SM22α by TGF-β1 was markedly attenuated in SYF cells (c-Src
−
, Yes
−
, and Fyn
−
) compared with Src
++
cells (c-Src
++
, Yes
−
, and Fyn
−
). PP1 also inhibited the TGF-β1–induced expression of serum response factor (SRF), a transcription factor regulating the SMC marker gene expression. Confocal immunofluorescence analysis showed that TGF-β1 stimulates production of hydrogen peroxide. Antioxidants such as catalase or NAD(P)H oxidase inhibitors such as apocynin inhibited the TGF-β1–induced expression of SM22α. Furthermore, we demonstrate that TGF-β1 induction of the plasminogen activator inhibitor-1 (PAI-1) gene, which is known to be dependent on Smad but not on SRF, is inhibited by PP1 and apocynin.

Conclusion—

Our results suggest that TGF-β1 activates c-Src and generates hydrogen peroxide through NAD(P)H oxidase, and these signaling pathways lead to the activation of specific sets of genes, including SM22α and PAI-1.
Inherited Apolipoprotein A-V Deficiency in Severe Hypertriglyceridemia
Authors: Oliva Claudio Priore , Pisciotta Livia , Volti Giovanni Li , Sambataro Maria Paola , Cantafora Alfredo , Bellocchio Antonella , Catapano Alberico , Tarugi Patrizia , Bertolini Stefano , Calandra Sebastiano
Published: January 2005

Objective—

Mutations in
LPL
or
APOC2
genes are recognized causes of inherited forms of severe hypertriglyceridemia. However, some hypertrigliceridemic patients do not have mutations in either of these genes. Because inactivation or hyperexpression of
APOA5
gene, encoding apolipoprotein A-V (apoA-V), causes a marked increase or decrease of plasma triglycerides in mice, and because some common polymorphisms of this gene affect plasma triglycerides in humans, we have hypothesized that loss of function mutations in
APOA5
gene might cause hypertriglyceridemia.

Methods and Results—

We sequenced
APOA5
gene in 10 hypertriglyceridemic patients in whom mutations in
LPL
and
APOC2
genes had been excluded. One of them was found to be homozygous for a mutation in
APOA5
gene (c.433 C>T, Q145X), predicted to generate a truncated apoA-V devoid of key functional domains. The plasma of this patient was found to activate LPL in vitro less efficiently than control plasma, thus suggesting that apoA-V might be an activator of LPL. Ten carriers of Q145X mutation were found in the patient’s family; 5 of them had mild hypertriglyceridemia.

Conclusions—

As predicted from animal studies, apoA-V deficiency is associated with severe hypertriglyceridemia in humans. This observation suggests that apoA-V regulates the secretion and/or catabolism of triglyceride-rich lipoproteins.
Association Between the CYP3A5 Genotype and Blood Pressure
Authors: Ho Herbert , Pinto Amar , Hall Stephen D. , Flockhart David A. , Li Lang , Skaar Todd C. , Cadman Peter , O’Connor Daniel T. , Wagner Urban , Fineberg Naomi S. , Weinberger Myron H.
Published: January 2005

We tested the hypothesis that the presence of a
CYP3A5
*
1
allele is associated with increases in blood pressure in 2 studies of subjects with a total of 683 participants. The first study involving 271 subjects was part of a longitudinal study conducted at Indiana University Medical Center that consisted of 2 phases. The first phase studied the relationship of salt sensitivity with blood pressure, whereas the second phase, conducted ≈26 years later, studied the relationship between blood pressure, carbohydrate intolerance, and vascular compliance in the same subjects. The second study was a cross-sectional evaluation of 412 normotensive and hypertensive subjects conducted at the University of California San Diego. The second study (Mantel–Haenszel χ
2
test;
P
=0.05) showed that a greater proportion of black participants with poor blood pressure control had
CYP3A5
*
1
/*
1
genotype. Evaluation of the untreated blood pressure from phase 1 of the first study showed that the blacks with
CYP3A5
*
3
/*
3
(146±35 mm Hg) had a higher systolic blood pressure than those with the *
1
/*
3
(119±14.1 mm Hg;
P
=0.0006) and *
1
/*
1
(125±17.4 mm Hg;
P
=0.009) genotypes. For blacks in study 2, the
CYP3A5
*
1
allele was more common in hypertensives (Fisher exact test;
P
=0.025) than normotensives. In whites there was no association between
CYP3A5
genotype and blood pressure in either study. We conclude that although untreated blood pressure may be higher in blacks with the
CYP3A5
*
3
/*
3
genotype, the
CYP3A5
*
1
allele may be associated with hypertension that is more refractory to treatment in this ethnic group.
Microangiopathic Hemolysis and Renal Failure in Malignant Hypertension
Authors: van den Born Bert Jan H. , Honnebier Uwkje P.F. , Koopmans Richard P. , van Montfrans Gert A.
Published: January 2005

Renal dysfunction is an important cause of morbidity and mortality in patients with malignant hypertension. Microangiopathic hemolysis (MAHA) related to malignant hypertension may cause renal insufficiency by obstruction of interlobular arteries. We hypothesized that the presence of MAHA is an important indicator of renal dysfunction and recovery in malignant hypertension. We retrospectively analyzed 97 patients admitted between April 1994 and April 2004 with malignant hypertension. MAHA was defined as a low platelet count (<150×10
9
/L) with either an elevated lactic dehydrogenase (>220 U/L) or presence of schistocytes. MAHA was present in 26 of 97 patients (27%). Serum creatinine levels at admission were significantly higher in those with than in those without MAHA: median serum creatinine 690 μmol/L (interquartile range [IQR] 394 to 1105) and 120 μmol/L (IQR 82 to 211), respectively (
P
<0.01). Macroalbuminuria was present in 88% with versus 41% without MAHA (
P
<0.01). Patients with MAHA were more often black (73%;
P
<0.01) and had higher systolic blood pressure (mean 242 mm Hg versus 225 mm Hg;
P
<0.01). Dialysis was needed in 15 patients with MAHA (58%) versus 2 patients (3%) without MAHA. In 6 patients with MAHA, dialysis could be stopped. Cox regression analysis showed that MAHA and systolic blood pressure were the most important indicators of renal improvement during follow-up, with a hazard ratio of 0.24 (95% confidence interval [CI], 0.08 to 0.75;
P
=0.01) and 1.02 per mm Hg increase in systolic blood pressure (95% CI, 1.01 to 1.05;
P
=0.01). In conclusion, MAHA is an important indicator of renal insufficiency and recovery in patients with malignant hypertension.
Noninvasive Evaluation of the Coronary Arteries With Multislice Computed Tomography in Hypertensive Patients
Authors: Schuijf Joanne D. , Bax Jeroen J. , Jukema J. Wouter , Lamb Hildo J. , Vliegen Hubert W. , van der Wall Ernst E. , de Roos Albert
Published: January 2005

Because patients with hypertension are at increased risk for coronary artery disease, early and noninvasive identification of the disease in patients with hypertension is important. Recently, multislice computed tomography (MSCT) has been demonstrated to allow both noninvasive coronary angiography and assessment of left ventricular function. The purpose of the present study therefore was to demonstrate the feasibility of this approach in patients with hypertension with known or suspected coronary artery disease and to compare the results to invasive coronary angiography and 2-dimensional echocardiography, respectively. MSCT was performed in 31 patients with confirmed hypertension. From the MSCT images, the presence of significant coronary stenoses (≥50% luminal narrowing) and regional wall motion abnormalities were evaluated and compared with invasive coronary angiography and 2-dimensional echocardiography. In addition, left ventricular ejection fraction was calculated from the MSCT images. A total of 243 (88%) coronary artery segments could be evaluated with MSCT. Sensitivity and specificity for the detection of significant coronary artery stenoses were 93% and 96%. On a per-patient basis, MSCT was accurate in 28 (90%) patients. Mean left ventricular ejection fraction was 46±14% (range, 16% to 64%). The agreement for assessing regional wall motion was 91% (kappa statistic, 0.81). In conclusion, simultaneous, noninvasive evaluation of coronary artery stenoses and left ventricular function with MSCT is accurate in patients with hypertension. This noninvasive approach may allow triage of patient treatment in terms of conservative versus invasive management.
Elimination of a long-range cis-regulatory module causes complete loss of limb-specificShhexpression and truncation of the mouse limb
Authors: Sagai Tomoko , Hosoya Masaki , Mizushina Youichi , Tamura Masaru , Shiroishi Toshihiko
Published: January 2005

Mutations in a conserved non-coding region in intron 5 of the Lmbr1 locus, which is 1 Mb away from the sonic hedgehog(Shh) coding sequence, are responsible for mouse and human preaxial polydactyly with mirror-image digit duplications. In the mouse mutants,ectopic Shh expression is observed in the anterior mesenchyme of limb buds. Furthermore, a transgenic reporter gene flanked with this conserved non-coding region shows normal polarized expression in mouse limb buds. This conserved sequence has therefore been proposed to act as a long-range,cis-acting regulator of limb-specific Shh expression. Previous phylogenetic studies have also shown that this sequence is highly conserved among tetrapods, and even in teleost fishes. Paired fins of teleost fishes and tetrapod limbs have evolved from common ancestral appendages, and polarized Shh expression is commonly observed in fins. In this study, we first show that this conserved sequence motif is also physically linked to the Shh coding sequence in a teleost fish, the medaka, by homology search of a newly available genomic sequence database. Next, we show that deletion of this conserved intronic sequence by targeted mutation in the mouse results in a complete loss of Shh expression in the limb bud and degeneration of skeletal elements distal to the stylopod/zygopod junction. This sequence contains a major limb-specific Shh enhancer that is necessary for distal limb development. These results suggest that the conserved intronic sequence evolved in a common ancestor of fishes and tetrapods to control fin and limb development.
Formation of Alliances in Internet-Based Supply Exchanges
Authors: Granot Daniel , Sošić Greys
Published: January 2005

In different industries, such as automobiles, chemicals, or retailing, competitors are joining forces in establishing electronic marketplaces to reduce inefficiencies in the purchasing process and cut costs by combining their buying power. Joining such an alliance leads to reduced costs, including those of possible rivals, because members share the development and operating costs. A company that joins an alliance agrees to share its suppliers with others, which may lead to more intense competition among the increased number of suppliers, and it may further benefit an alliance member at the expense of companies left outside the alliance. Natural questions that could arise, then, are when would a firm prefer to take part in an electronic marketplace joint venture; when would it prefer that other firms, possibly rivals, join the venture; and what are the financial consequences of either joining an alliance or remaining independent? In an attempt to gain a better understanding of the issues, we have developed a model of three retailers whose products may have a certain degree of substitutability. We provide some conditions, in terms of product substitutability and compatibility of retailers, that would lead to the formation of a three-member alliance, or a two-member alliance, or no alliance at all. We also study the effect of alliance structure and compatibility of retailers on the profit of a company.
Supply Chain Coordination with Revenue-Sharing Contracts: Strengths and Limitations
Authors: Cachon Gérard P. , Lariviere Martin A.
Published: January 2005

Under a revenue-sharing contract, a retailer pays a supplier a wholesale price for each unit purchased, plus a percentage of the revenue the retailer generates. Such contracts have become more prevalent in the videocassette rental industry relative to the more conventional wholesale price contract. This paper studies revenue-sharing contracts in a general supply chain model with revenues determined by each retailer's purchase quantity and price. Demand can be deterministic or stochastic and revenue is generated either from rentals or outright sales. Our model includes the case of a supplier selling to a classical fixed-price newsvendor or a price-setting newsvendor. We demonstrate that revenue sharing coordinates a supply chain with a single retailer (i.e., the retailer chooses optimal price and quantity) and arbitrarily allocates the supply chain's profit. We compare revenue sharing to a number of other supply chain contracts (e.g., buy-back contracts, price-discount contracts, quantity-flexibility contracts, sales-rebate contracts, franchise contracts, and quantity discounts). We find that revenue sharing is equivalent to buybacks in the newsvendor case and equivalent to price discounts in the price-setting newsvendor case. Revenue sharing also coordinates a supply chain with retailers competing in quantities, e.g., Cournot competitors or competing newsvendors with fixed prices. Despite its numerous merits, we identify several limitations of revenue sharing to (at least partially) explain why it is not prevalent in all industries. In particular, we characterize cases in which revenue sharing provides only a small improvement over the administratively cheaper wholesale price contract. Additionally, revenue sharing does not coordinate a supply chain with demand that depends on costly retail effort. We develop a variation on revenue sharing for this setting.