bluuebunny/crossref_metadata_2025 huggingface dataset:
SHIFT-ADD CORRELATION PATTERNS OF ORBITS OF ONE-DIMENSIONAL LINEAR CELLULAR AUTOMATA
Authors: BARBÉ ANDRÉ
Published: October 2004

We consider the two-dimensional state-time evolution pattern (orbit) of a one-dimensional linear cellular automaton (CA) defined over a finite commutative ring R, and correlate this to shifted versions of itself by adding the original pattern and its shifted versions. The resulting pattern is called the shift-add (correlation) pattern. A dual counterpart of this pattern is also introduced: it forms a so-called pseudo-CA orbit. We show that the set of shift-add patterns for different shifts interrelate like a pseudo-CA whose states are two-dimensional patterns over R. The set of dual shift-add patterns forms likewise a regular CA. Complementary ways of viewing the shift-add correlation space are also presented. Finally, the nature of shift-add correlation patterns for the newly defined class of pseudo-CA is investigated.
SYNCHRONIZATION OF CHAOTIC NEURAL NETWORKS AND APPLICATIONS TO COMMUNICATIONS
Authors: MILANOVIĆ VELJKO , ZAGHLOUL MONA E.
Published: October 2004

Methods for synchronizing discrete time chaotic neural networks are presented with possible applications in single- or multi-user private communications. Chaotic neurons, characterized with a piecewise-linear N-shaped transfer function, are connected into Hopfield-like networks with parameters set for chaos. The networks are used as transmitter and receiver circuits in chaotic communications schemes. The first algorithm is a modification of simple chaotic masking which makes synchronization robust and insensitive to the perturbation from the added information signal. A mathematical proof and simulation results of the scheme are shown for small networks. We have verified the method experimentally, using single- and two-neuron circuits. The second algorithm utilizes modulation of the transmitting chaotic network by a binary bit stream and detection of the corresponding synchronization error at the receiver. A method for multiple-user chaotic communication is also presented, utilizing chaotic neurons and spread spectrum techniques. The effects of additive noise in the proposed communication schemes are considered and simulated. Synchronization of larger networks and possible applications are also discussed.
TRANSIENT CHAOTIC MIXING IN OPEN HYDRODYNAMICAL FLOWS
Authors: PÉNTEK Á. , TÉL T. , TOROCZKAI Z.
Published: October 2004

We investigate particle motion and mixing in time-dependent open flows with uniform inflow and outflow velocities. The dynamics is typically chaotic, of the transient type that can be observed on finite time scales only. There exists an underlying chaotic set consisting of an infinity of unstable tracer orbits, restricted to a finite domain of the flow. Transient dynamics is accompanied by persistent fractality. The latter is reflected by tracer patterns and by the singularity distribution of the particles’ time delay function. As an illustrative example, we consider a planar incompressible flow modeling the leapfrogging motion of two vortex rings.
STABILIZATION OF PERIODIC ORBITS IN VARIABLE STRUCTURE SYSTEMS.
Authors: BATLLE CARLES , FOSSAS ENRIC , OLIVAR GERARD
Published: October 2004

A method to stabilize periodic orbits in switching topology systems is proposed. The method only requires knowledge of the times when the target orbit changes the topology and is specialized to bilinear systems, which constitute a general model for DC-DC power converters. Several simulations for the buck and Čuk converters are presented.
SENSOR AND CONTROL ASPECTS OF BIPED ROBOT "JOHNNIE"
Authors: PFEIFFER FRIEDRICH , LÖFFLER KLAUS , GIENGER MICHAEL , ULBRICH HEINZ
Published: October 2004

The biped robot "Johnnie" is designed to achieve a dynamically stable gait pattern, allowing for high walking velocities. Very accurate and fast sensors were developed for the machine. In particular the design of the 3D-orientation sensor and the 6-axes force-torque sensor are presented. The control scheme is based on the information from these sensors to deal with unstructured terrain and disturbances. Two different implementations are investigated: a computed torque approach and a trajectory control with adaptive trajectories. Walking speeds of 2.2 km/h have been achieved in experiments.
The role of angiotensin converting enzyme 2 in the generation of angiotensin 1–7 by rat proximal tubules
Authors: Li Ningjun , Zimpelmann Joseph , Cheng Keding , Wilkins John A. , Burns Kevin D.
Published: October 2004

ANG converting enzyme (ACE) 2 (ACE2) is a homologue of ACE, which is not blocked by conventional ACE inhibitors. ACE2 converts ANG 1–10 (ANG I) to ANG 1–9, which can be hydrolyzed by ACE to form the biologically active peptide ANG 1–7. ACE2 is expressed in the kidney, but its precise intrarenal localization is unclear, and the role of intrarenal ACE2 in the production of ANG 1–7 is unknown. The present studies determined the relative distribution of ACE2 in the rat kidney and defined its role in the generation of ANG 1–7 in proximal tubule. In microdissected rat nephron segments, semiquantitative RT-PCR revealed that ACE2 mRNA was widely expressed, with relatively high levels in proximal straight tubule (PST). Immunohistochemistry demonstrated ACE2 protein in tubular segments, glomeruli, and endothelial cells. Utilizing mass spectrometry, incubation of isolated PSTs with ANG I (10−6M) led to generation of ANG 1–7 (sensitivity of detection > 1 × 10−9M), accompanied by the formation of ANG 1–8 (ANG II) and ANG 1–9. The ACE2 inhibitor DX600 completely blocked ANG I-mediated generation of ANG 1–7. Incubation of PSTs with ANG 1–9 also led to generation of ANG 1–7, an effect blocked by the ACE inhibitor captopril or enalaprilat, but not by DX600. Incubation of PSTs with ANG II or luminal perfusion of ANG II did not result in detection of ANG 1–7. The results indicate that ACE2 is widely expressed in rat nephron segments and contributes to the production of ANG 1–7 from ANG I in PST. ANG II may not be a major substrate for ACE2 in isolated PST. The data suggest that ACE2-mediated production of ANG 1–7 represents an important component of the proximal tubular renin-ANG system.
Megalin binds and internalizes angiotensin II
Authors: Gonzalez-Villalobos Romer , Klassen R. Bryan , Allen Patricia L. , Navar L. G. , Hammond Timothy G.
Published: October 2004

Megalin is an abundant membrane protein heavily involved in receptor-mediated endocytosis. The major functions of megalin in vivo remain incompletely defined as megalin typically faces specialized milieus such as glomerular filtrate, airways, epididymal fluid, thyroid colloid, and yolk sac fluid, which lack many of its known ligands. In the course of studies on ANG II internalization, we were surprised when only part of the uptake of labeled ANG II into immortalized yolk sac cells (BN-16 cells) was blocked by specific peptide inhibitors and direct competitors of the angiotensin type 1 receptor. This led us to test if megalin was a receptor for ANG II. Four lines of direct evidence demonstrate that megalin and, to a lesser extent, its chaperone protein cubilin are receptors for ANG II. First, in BN-16 cells anti-megalin and anti-cubilin antisera interfere with ANG II uptake. Second, also in BN-16 cells, pure ANG II competes for uptake of a known megalin ligand. Third, in proximal tubule cell brush-border membrane vesicles extracted from mice, anti-megalin antisera interfere with ANG II binding. Fourth, purified megalin binds ANG II directly in surface plasmon resonance experiments. The finding that megalin is a receptor for ANG II suggests a major new function for the megalin pathway in vivo. These results also indicate that ANG II internalization in some tissues is megalin dependent and that megalin may play a role in regulating proximal tubule ANG II levels.
Effect of altitude on thrombopoietin and the platelet count in healthy volunteers
Authors: Hartmann Sabine , Huch Renate , Breymann Christian , Krafft Alexander
Published: October 2004

Although there is evidence that altitude increases the platelet count, its effect on the platelet precursor stimulating factor, thrombopoietin (TPO), is unclear. Unlike erythropoietin, TPO appears largely unresponsive to exogenous signals. In a study in 16 healthy volunteers,we report the effects of altitude exposure at between 1000 and 1822 m for 1 or 2 weeks on TPO, the platelet count (+ indices), erythropoietin, hemoglobin, hematocrit and erythrocytes (+ indices).There were significant post-expo-sure increases in TPO (57.9 vs 37.1 U/l; P = 0.0006), platelet count (219.1 vs 208.0 x 103/ml; P = 0.031) and erythropoietin (16.1 vs 9.9 U/l; P = 0.0032).There was a positive correlation between the increases in TPO and platelet count (r = 0.52, P = 0.043). Hemoglobin and hematocrit remained unchanged. Our results provide clear evidence for a relationship, presumably driven by hypoxia, between altitude exposure,TPO production and the platelet count.
Temporal changes in pulmonary expression of key procoagulant molecules in rabbits with endotoxin-induced acute lung injury: elevated expression levels of protease-activated receptors
Authors: Jesmin Subrina , Matsuda Naoyuki , Sakuma Ichiro , Kobayashi Shigeaki , Sakuraya Fumika , Hattori Yuichi , Gando Satoshi
Published: October 2004

Recently a new concept has emerged implicating thrombin signaling as the “bridge” that connects tissue damage to hemostatic and inflammatory responses. In view of this concept, we hypothesized that induction of protease-activated receptor (PAR) expression may play a critical role in endotoxin-induced tissue injury through the cellular actions of thrombin. Thus, in this study, temporal changes in expression of key precoagulant molecules, including PARs, in lungs from rabbits rendered endotoxemic by 100 μg/kg lipopolysaccharide (LPS) were examined with measurements of variables reflecting acute lung injury (ALI). ALI induction by LPS was confirmed by blood gas derangement, lung vascular hyperpermeability, and histopathological changes, and was characterized by the deposition of fibrin in the alveolar spaces, bronchioles and vessels. Plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) were highly expressed in lungs after LPS injection. While the peaks in levels of PAI-1 and TF were comparable (12∼13-fold from control), their expression time-courses were different: PAI-1 exhibited a bell-shaped expression pattern and peak at 6 h, whereas TF level reached maximum at 10 h. Of note, LPS induced a rapid and significant increase in levels of PAR-1 compared to control, with a peak level at 1 h (3.3-fold). Although declining thereafter, it remained significantly higher than the control level throughout the study period. Expressions of PAR-2, -3, and -4 were also increased by LPS with different time courses from PAR-1 expression. Immunofluorescence staining for PAR-1 were localized in blood vessels, bronchial epithelium, and alveolar pneumocytes after LPS. These results suggest that the increased expression levels of PARs, in addition to PAI-1 and TF, may, in part, underlie the development of ALI occurring during endotoxemia.
Strenuous, acute exercise suppresses polymorphonuclear leukocyte respiratory burst under adherence to surface-adherent platelets in men
Authors: Wang Jong-Shyan
Published: October 2004

Interaction between polymorphonuclear leukocyte (PMN) and platelets is important in the pathogenesis of thrombosis and inflammation. This study investigates how strenuous, acute exercise affects PMN oxidative burst activity under adherence to surface-adherent platelets. Thirty sedentary healthy men exercised strenuously (up to maximal oxygen consumption) on a bicycle ergometer. Before and immediately after exercise, the kinetics of oxidant production, phosphorylation of various protein kinase C (PKC) isoforms, and translocation of p47phox in PMNs under adherence to surface-adherent platelets were measured using fluorescence microscopy combined with computerized image analysis. Analytical results can be summarized as follows: (i) either treating the platelet with P-selectin (CD62P) and glycoprotein IIb/IIIa (CD41) antibodies or treating the PMN with β2-integrin (CD18) and Mac-1 (CD11b) antibodies and PKCζpseudosubstrate effectively inhibits platelet-promoted oxidant production of PMN; (ii) PMNs adhesion to surface-adherent platelets is associated with a higher amount of phospho-PKCζand a larger ratio of membrane to cytosolic p47phox than suspended PMNs; (iii) strenuous, acute exercise decreases platelet-promoted oxidant production of PMN and is accompanied by suppressed phosphorylation of PKCζ, translocation of p47phox, and inhibition of PKCζpseudosubstrate to oxidant production; (iv) no significant changes occur in PKCα/βII and δ phosphorylation of adherent PMNs following this exercise. Therefore, we conclude that strenuous, acute exercise suppresses platelet-promoted oxidative burst of PMN, possibly by reducing phosphorylation of PKCζand translocation of the cytosolic p47phox to the plasma membrane, thus inhibiting the assembly and activation of NADPH oxidase in PMN.
Neutrophils stimulated by apolipoprotein(a) generate fragments that are stronger inhibitors of plasmin formation than apo(a)
Authors: Lamanuzzi Leila , Mtairag El Mostafa , Pepe Gabriella , Anglés-Cano Eduardo
Published: October 2004

Apolipoprotein(a), the plasminogen-like component of lipoprotein(a), is transformed into fragments by polymorphonuclear neutrophils (PMNs) elastase. Since stimulated PMNs express urokinase-type plasminogen activator (uPA), we sought to investigate the relevance of apo(a) fragmentation on plasminogen activation by neutrophils. Freshly isolated human PMNs stimulated by a 10 kringle recombinant apo(a), r-apo(a), activate plasminogen in a specific and saturable manner (Km = 476 ± 42 nM, Vmax = 896 ± 18 pmol min-1). This activation is prevented by amiloride, an inhibitor of u-PA, and ɛ-aminocaproic acid, ɛ-ACA, a lysine analogue that blocks plasminogen binding to PMNs. Stimulation of PMNs by apo(a) results in the formation of elastase-derived apo(a) fragments. These fragments produce a concentration-dependent decrease in the formation of plasmin. Addition of elastase inhibitors to PMNs prevented degradation of apo(a) and partially restored the formation of plasmin. In a similar manner, isolated r-apo(a) fragments were able to produce a 100% decrease in plasmin generation as compared to intact r-apo(a). These data indicate that apo(a) fragments produce a more pronounced inhibition in the generation of cellbound plasmin by uPA than the parent apo(a). These effects of apo(a) and its fragments were neutralised by a monoclonal antibody directed against the lysine-binding site of apo(a). This mechanism may be of biological relevance to the effects of Lp(a) in conditions where PMNs accumulate and release elastase, i.e. thrombus lysis and inflammatory lesions.
Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients
Authors: Kurnik Daniel , Loebstein Ronen , Rabinovitz Hadas , Austerweil Naomi , Almog Shlomo , Halkin Hillel
Published: October 2004

Most multivitamin supplements contain far less vitamin K1 than thought to affect warfarin anticoagulation. Having described 3 patients with multivitamin-warfarin interactions, we hypothesized that vitamin K1–depleted patients are sensitive to even small increments. Therefore, we compared the effect of a vitamin K1-containing multivitamin on warfarin anticoagulation between patients with low versus normal vitamin K1 status. We screened 102 warfarin-treated patients and recruited nine with “low” (< 1.5 mcg/L, 10th percentile) (group 1) and 7 with “normal” (>4.5 mcg/L, median) (group 2) total vitamin K1 plasma levels (vitamin K1 + vitamin K1 2,3-epoxide). Patients received one multivitamin tablet containing 25 mcg of vitamin K1 daily, for 4 weeks (period 1). A predefined algorithm was used to adjust warfarin doses if the INR was outside the therapeutic range. Patients requiring warfarin increments were then switched to 4 weeks of a vitamin K1-free multivitamin supplement (period 2). During period 1, subtherapeutic INRs occurred in 9/9 and 1/7 patients in group 1 and 2, respectively (p <0.001). In group 1, INR decreased by a median of 0.51 (p <0.01), and warfarin dose had to be raised by 5.3% (p <0.01), whereas INR and warfarin dose did not change significantly in group 2. During period 2 (7 patients), there were trends towards decreased total vitamin K1 and rising INRs associated with significantly lower warfarin doses. We conclude that vitamin K1-containing multivitamins reduce INR in patients with low vitamin K1 status. Our study suggests that vitamin Kdepleted patients are sensitive to even small changes in vitamin K1 intake.
Human Study of Biatrial Electrical Coupling
Authors: Lemery Robert , Soucie Luc , Martin Bruno , Tang Anthony S.L. , Green Martin , Healey Jeff
Published: October 2004

Background—

The relative contribution of the atrial septum and interatrial connections to biatrial activation is a fundamental concept of human cardiac electrophysiology that has yet to be fully characterized. The purpose of the present study was to determine how both atria are coupled electrically.

Methods and Results—

Twenty patients (16 men; mean age 54±11years) with a history of symptomatic atrial fibrillation (AF) underwent simultaneous biatrial noncontact mapping before catheter ablation of AF. The multiple electrode array catheters were positioned, respectively, in the left atrium (LA; transseptally) and the right atrium (RA). In all but 2 patients, isopotential maps revealed that endocardial septal activations of the RA and LA were separate, independent, and asynchronous of each other. Interatrial conduction was related to the site of initial atrial depolarization, revealing conduction over Bachmann’s bundle in all patients during sinus rhythm, high RA pacing, and pacing from the LA appendage. Pacing from the coronary sinus was associated with conduction over the interatrial connection at the level of the coronary sinus in all patients, and conduction over Bachmann’s bundle also occurred in 5 (26%) of 19 patients. Interatrial conduction over the fossa ovalis occurred in only 2 (2%) of the 116 segments analyzed.

Conclusions—

Electrical coupling of the RA and LA in humans is predominantly provided by muscular connections at the level of Bachmann’s bundle and the coronary sinus. The true septum (the fossa ovalis and its limbus) of the RA and LA is asynchronous and discordant, usually without contralateral conduction during sinus rhythm or atrial pacing.
Blood Pressure-Related Cognitive Decline
Authors: Elias Penelope K. , Elias Merrill F. , Robbins Michael A. , Budge Marc M.
Published: October 2004

Systolic and diastolic blood pressures have been inversely related to cognitive performance in prospective and cross-sectional studies. However, in large, community-based samples, these findings have been limited to older adults. In this 20-year longitudinal study, we examined the relationship between baseline blood pressure and cognitive decline for 529 participants using 2 age groups (18 to 46 years and 47 to 83 years). Cognitive performance was measured over multiple examinations with the Wechsler Adult Intelligence Scale from which 4 scores were derived by factor analysis. A 2-stage growth curve method of analysis was used to model cognitive change. Results indicated that higher levels of baseline systolic blood pressure, diastolic blood pressure, mean arterial pressure, and blood pressure categories as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure were significantly associated with decline in Visualization/Fluid abilities in both younger and older age groups. Young adults are as susceptible to blood pressure-related longitudinal decline in cognitive performance as are older adults.
Plasma cGMP and Large Artery Remodeling in Asymptomatic Men
Authors: Devynck Marie-Aude , Simon Alain , Pernollet Marie-Gabrielle , Chironi Gilles , Gariepy Jérôme , Rendu Francine , Levenson Jaime
Published: October 2004

cGMP regulates vascular smooth muscle tone and arterial wall response to proliferative signals. We determined plasma cGMP and carotid artery intima-media thickness (IMT) and diameter in 84 asymptomatic men submitted to investigation of their cardiovascular risk profiles. Plasma cGMP was positively associated with IMT (
P
<0.01) and diameter (
P
<0.05), independently of coexisting risk factors. These associations were reinforced in the subgroup of subjects with high-sensitivity C-reactive protein level or multiple atherosclerotic plaques. A positive relationship existed between diameter and IMT (
P
<0.01) and disappeared after cGMP adjustment. This suggests a link between cGMP pathway and arterial wall geometry that is revealed by vascular injury conditions and may participate in early large artery remodeling.
Bu(o)ying Condoms: A Prophylactic Performance of Sexuality (or Performance as Cultural Prophylactic Agency)
Authors: Alexander Bryant Keith
Published: October 2004

This article uses the experience of buying condoms at the grocery store and the free availability of condoms in gay bars as both a literal and figurative analogy for the tensive social issue of negotiating sex and sexuality. It posits the condom both as preventive agent for the spread of disease and as an erotic trigger for the social sexual imaginary. In the process, the project promotes the metaphorical construction of performance as cultural prophylactic agency and calls for a radical performative reflexivity both in performance of everyday life and specifically in academic performative engagement.
Culture, State, Globalization: The Articulation of Global Capitalism
Authors: Kien Grant
Published: October 2004

Suggesting cultural analysis of the phenomenon of globalization needs to take into account more than studies of subjectivity and communications technology, the author suggests a deconstructive methodology that seeks reconciliation of postmodernism with structuralism and idealism with materialism. Demonstrating points of contact between various social actors in the globalization arena, a sketch is made of the state as a pluralist agent articulating the process of globalizing capital. Motivations to globalize are said to point to a real social by which the political structure of the state is revealed. Subversion of the dominant discourse through self-determined practices of liberty are suggested as a means of constructing alternatives to global capital.
A role for the thiol isomerase protein ERP5 in platelet function
Authors: Jordan Peter A. , Stevens Joanne M. , Hubbard Gary P. , Barrett Natasha E. , Sage Tanya , Authi Kalwant S. , Gibbins Jonathan M.
Published: October 2004

Formation and rearrangement of disulfide bonds during the correct folding of nascent proteins is modulated by a family of enzymes known as thiol isomerases, which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5 (ERP5), and ERP57. Recent evidence supports an alternative role for this family of proteins on the surface of cells, where they are involved in receptor remodeling and recognition. In platelets, blocking PDI with inhibitory antibodies inhibits a number of platelet activation pathways, including aggregation, secretion, and fibrinogen binding. Analysis of human platelet membrane fractions identified the presence of the thiol isomerase protein ERP5. Further study showed that ERP5 is resident mainly on platelet intracellular membranes, although it is rapidly recruited to the cell surface in response to a range of platelet agonists. Blocking cell-surface ERP5 using inhibitory antibodies leads to a decrease in platelet aggregation in response to agonists, and a decrease in fibrinogen binding and P-selectin exposure. It is possible that this is based on the disruption of integrin function, as we observed that ERP5 becomes physically associated with the integrin β3 subunit during platelet stimulation. These results provide new insights into the involvement of thiol isomerases and regulation of platelet activation.
A novel apoptosis pathway activated by the carboxyl terminus of p21
Authors: Dong Chen , Li Qing , Lyu Shu-chen , Krensky Alan M. , Clayberger Carol
Published: October 2004

Delivery of biologically active peptides into cells may help elucidate intracellular signal transduction pathways, identify additional in vivo functions, and develop new therapeutics. Although p21 was first identified as a major regulator of cell cycle progression, it is now clear that p21 subserves multiple functions. The amino terminus of p21 interacts with cyclins and cyclin-dependent kinases, while the carboxyl terminus interacts with proliferating cell nuclear antigen (PCNA), growth arrest and DNA damage–inducible gene 45 (GADD45), calmodulin, SET, and CCAAT/enhancer binding protein-α (C/EBP-α). A chimeric peptide, p21-IRS, consisting of the carboxyl terminal domain of p21 conjugated to a pentapeptide (RYIRS) rapidly enters lymphoid cells and activates apoptosis. In the present study, we investigate the molecular events involved in p21-activated apoptosis. Comparison of p21-IRS with other known proapoptotic agents demonstrates that p21-IRS activates a novel apoptotic pathway: mitochondria are central to the process, but caspases and a decrease in Δψm are not involved. Targeting the p21 peptide to specific cell populations may allow development of novel therapies to eliminate aberrant cells in human diseases.
Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-γ-producing lymphocytes and IL-6- and TNF-α-producing macrophages
Authors: Billiau An D. , Roskams Tania , Van Damme-Lombaerts Rita , Matthys Patrick , Wouters Carine
Published: October 2004

Macrophage activation syndrome (MAS) is a rare and potentially fatal disorder, thought to result from uncontrolled activation and proliferation of T cells and excessive activation of macrophages. The term MAS designates a clinicopathologic entity that occurs in different hemophagocytic syndromes (HSs). Primary hemophagocytic lymphohistiocytosis (HLH) is recognized to have an immunogenetic basis, but in the secondary HS (also referred to as secondary HLH), the cause is unknown. The pathogenesis of the accelerated disease phase typical of MAS remains incompletely understood. This report describes the immunohistochemical findings on liver tissues from 5 children, each of whom presented with MAS in the context of a different type of HS. The data provide direct evidence for the involvement of activated CD8+ lymphocytes through the production of interferon-γ and of macrophages through hemophagocytosis and production of interleukin 6 and tumor necrosis factor-α, and underscore the view that MAS in different HSs share a common effector pathway. (Blood. 2005;105:1648-1651)
Microarrays for global expression constructed with a low redundancy set of 27,500 sequenced cDNAs representing an array of developmental stages and physiological conditions of the soybean plant
Authors: Vodkin Lila O , Khanna Anupama , Shealy Robin , Clough Steven J , Gonzalez Delkin Orlando , Philip Reena , Zabala Gracia , Thibaud-Nissen Françoise , Sidarous Mark , Strömvik Martina V , Shoop Elizabeth , Schmidt Christina , Retzel Ernest , Erpelding John , Shoemaker Randy C , Rodriguez-Huete Alicia M , Polacco Joseph C , Coryell Virginia , Keim Paul , Gong George , Liu Lei , Pardinas Jose , Schweitzer Peter
Published: October 2004

Background

Microarrays are an important tool with which to examine coordinated gene expression. Soybean (Glycine max) is one of the most economically valuable crop species in the world food supply. In order to accelerate both gene discovery as well as hypothesis-driven research in soybean, global expression resources needed to be developed. The applications of microarray for determining patterns of expression in different tissues or during conditional treatments by dual labeling of the mRNAs are unlimited. In addition, discovery of the molecular basis of traits through examination of naturally occurring variation in hundreds of mutant lines could be enhanced by the construction and use of soybean cDNA microarrays.

Results

We report the construction and analysis of a low redundancy 'unigene' set of 27,513 clones that represent a variety of soybean cDNA libraries made from a wide array of source tissue and organ systems, developmental stages, and stress or pathogen-challenged plants.

The set was assembled from the 5' sequence data of the cDNA clones using cluster analysis programs. The selected clones were then physically reracked and sequenced at the 3' end. In order to increase gene discovery from immature cotyledon libraries that contain abundant mRNAs representing storage protein gene families, we utilized a high density filter normalization approach to preferentially select more weakly expressed cDNAs. All 27,513 cDNA inserts were amplified by polymerase chain reaction. The amplified products, along with some repetitively spotted control or 'choice' clones, were used to produce three 9,728-element microarrays that have been used to examine tissue specific gene expression and global expression in mutant isolines.

Conclusions

Global expression studies will be greatly aided by the availability of the sequence-validated and low redundancy cDNA sets described in this report. These cDNAs and ESTs represent a wide array of developmental stages and physiological conditions of the soybean plant. We also demonstrate that the quality of the data from the soybean cDNA microarrays is sufficiently reliable to examine isogenic lines that differ with respect to a mutant phenotype and thereby to define a small list of candidate genes potentially encoding or modulated by the mutant phenotype.
Tuberculous peritonitis in a case receiving continuous ambulatory peritoneal dialysis(CAPD) treatment
Authors: Sahin Garip , Kiraz Nuri , Sahin Ilknur , Soydan Mehmet , Akgün Yurdanur
Published: October 2004

Background

Tuberculosis continues to be an important health problem in the world. Besides pulmonary involvement extrapulmonary involvement becomes an affair in developing countries, even in developed countries.

Case presentation

A thirty-six year old male patient was admitted with abdominal pain, diarrhea, nausea, vomiting and fever which had started one week before. The patient had been followed up with predialisis Chronic Renal Failure(CRF) diagnosis for 4 years and receiving continuous ambulatory peritoneal dialysis (CAPD) treatment for 4 months. In peritoneal fluid, 1600/mm3 cells were detected and 70% of them were polymorphonuclear leukocytosis. The patient begun nonspesific antibiotherapy but no benefit was obtained after 12 days and peritoneal fluid bacterial cultures remained negative. Peritoneal smear was positive for Asid-fast basilli (AFB), and antituberculosis therapy was started with isoniazid, rifampicine, ethambutol and pyrazinamide. After 15 days his peritoneal fluid cell count was decreased and his symptoms were relieved. Peritoneal fluid tuberculosis culture was found positive.

Conclusion

Considering this case, we think that in patients with CAPD catheter and peritonitis; when peritoneal fluid leukocytes are high and PMNL are dominant, AFB and tuberculosis culture must be investigated besides bacterial culture routinely.
Impact of seasonal variation, age and smoking status on human semen parameters: The Massachusetts General Hospital experience
Authors: Chen Zuying , Godfrey-Bailey Linda , Schiff Isaac , Hauser Russ
Published: October 2004

Background

To investigate the relationship of human semen parameters with season, age and smoking status.

Methods

The present study used data from subjects recruited into an ongoing cross-sectional study on the relationship between environmental agents and semen characteristics. Our population consisted of 306 patients who presented to the Vincent Memorial Andrology Laboratory of Massachusetts General Hospital for semen evaluation. Sperm concentration and motility were measured with computer aided sperm analysis (CASA). Sperm morphology was scored using Tygerberg Kruger strict criteria. Regression analyses were used to investigate the relationships between semen parameters and season, age and smoking status, adjusting for abstinence interval.

Results

Sperm concentration in the spring was significantly higher than in winter, fall and summer (p < 0.05). There was suggestive evidence of higher sperm motility and percent of sperm with normal morphology in the spring than in the other seasons. There were no statistically significant relationships between semen parameters and smoking status, though current smokers tended to have lower sperm concentration. We also did not find a statistically significant relationship between age and semen parameters.

Conclusions

We found seasonal variations in sperm concentration and suggestive evidence of seasonal variation in sperm motility and percent sperm with normal morphology. Although smoking status was not a significant predictor of semen parameters, this may have been due to the small number of current smokers in the study.
The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo
Authors: Hicks Anne E R , Abbitt Kate B , Dodd Paul , Ridger Victoria C , Hellewell Paul G , Norman Keith E
Published: October 2004

Selectins and their ligands support leuocyte rolling, facilitating the subsequent firm adhesion and migration that occur during inflammation. TBC-1269 (Bimosiamose), a structural mimetic of natural selectin ligands, inhibits P-, E-, and L-selectin in vitro, has anti-inflammatory effects in vivo, and recently underwent phase II clinical trials for childhood asthma and psoriasis. We studied whether the anti-inflammatory effects of TBC-1269 could be related to leukocyte rolling in vivo. Although TBC-1269 inhibited rolling of a murine leukocyte cell line on murine P-selectin in vitro and thioglycollate-induced peritonitis in vivo, it did not alter leukocyte rolling in mouse cremaster venules. TBC-1269 reduced neutrophil recruitment in thioglycollate-induced peritonitis in wild-type and P-selectin−/− mice but not in E-selectin−/− mice. We suggest that the in vivo effects of TBC-1269 may be mediated through E-selectin but do not appear to involve leukocyte rolling.
The Cellular Fate of Glucose and Its Relevance in Type 2 Diabetes
Authors: Bouché Clara , Serdy Shanti , Kahn C. Ronald , Goldfine Allison B.
Published: October 2004

Type 2 diabetes is a complex disorder with diminished insulin secretion and insulin action contributing to the hyperglycemia and wide range of metabolic defects that underlie the disease. The contribution of glucose metabolic pathways per se in the pathogenesis of the disease remains unclear. The cellular fate of glucose begins with glucose transport and phosphorylation. Subsequent pathways of glucose utilization include aerobic and anaerobic glycolysis, glycogen formation, and conversion to other intermediates in the hexose phosphate or hexosamine biosynthesis pathways. Abnormalities in each pathway may occur in diabetic subjects; however, it is unclear whether perturbations in these may lead to diabetes or are a consequence of the multiple metabolic abnormalities found in the disease. This review is focused on the cellular fate of glucose and relevance to human type 2 diabetes.
Stable chromosomal units determine the spatial and temporal organization of DNA replication
Authors: Sadoni Nicolas , Cardoso M. Cristina , Stelzer Ernst H. K. , Leonhardt Heinrich , Zink Daniele
Published: October 2004

DNA replication occurs in mammalian cells at so-called replication foci occupying defined nuclear sites at specific times during S phase. It is an unresolved problem how this specific spatiotemporal organization of replication foci is determined. Another unresolved question remains as to what extent DNA is redistributed during S phase. To investigate these problems, we visualized the replicating DNA and the replication machinery simultaneously in living HeLa cells. Time-lapse analyses revealed that DNA was not redistributed to other nuclear sites during S phase. Furthermore, the results showed that DNA is organized into stable aggregates equivalent to replication foci. These aggregates, which we call sub-chromosomal foci, stably maintained their replication timing from S phase to S phase. During S-phase progression, the replication machinery sequentially proceeded through spatially adjacent sets of sub-chromosomal foci. These findings imply that the specific nuclear substructure of chromosomes and the order of their stable subunits determine the spatiotemporal organization of DNA replication.
Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line
Authors: Llorente Alicia , de Marco María C. , Alonso Miguel A.
Published: October 2004

MAL, BENE and MAL2 are raft-associated integral membrane proteins of the MAL family of proteins involved in membrane trafficking processes. We show here that the human prostate carcinoma PC-3 cell line expresses the transcripts for the three proteins simultaneously. MAL, BENE and MAL2 co-fractionated with caveolin-1 in the raft fraction of PC-3 cells, and immunofluorescence analysis showed colocalization of these proteins with caveolin-1 in a multivesicular intracellular compartment. Markers of the Golgi apparatus, early and recycling endosomes and lipid droplets were excluded from this compartment. Prostate epithelial cells contain vesicular organelles enriched in raft components named prostasomes that are secreted in the prostate fluid. Interestingly, the prostasome fraction isolated from the culture supernatant of PC-3 cells consisted mainly of 30-130 nm cup-shaped vesicles that were positive for MAL, caveolin-1 and CD59, a glycosylphosphatidylinositol-anchored protein previously found in prostasomes. CD63, an integral membrane protein found in multivesicular bodies/lysosomes and secretory granules was also found in PC-3 cell-derived prostasomes. Prostasome secretion was not inhibited by brefeldin A, a compound that blocks the conventional secretory pathway. However, wortmannin, an inhibitor of phosphatidylinositol-3 kinase, reduced the secretion of prostasomes in PC-3 cells. Our results suggest that MAL family proteins are associated with caveolin-1 in a multivesicular compartment that may be involved in prostasomal secretion in PC-3 cells.
Demonstration of BACE (β-secretase) phosphorylation and its interaction with GGA1 in cells by fluorescence-lifetime imaging microscopy
Authors: von Arnim Christine A. F. , Tangredi Michelle M. , Peltan Ithan D. , Lee Bonny M. , Irizarry Michael C. , Kinoshita Ayae , Hyman Bradley T.
Published: October 2004

β-Secretase (BACE) carries out the first of two proteolysis steps to generate the amyloid-β peptides that accumulate in the senile plaques in Alzheimer's disease (AD). Because most BACE activity occurs in endosomes, signals regulating its trafficking to these compartments are important to an understanding of AD pathogenesis. A DISLL sequence near the BACE C-terminus mediates binding of BACE to the VHS domains of Golgi-localized γ-ear-containing ARF-binding (GGA) proteins, which are involved in the sorting of proteins to endosomes. Phosphorylation of the motif's serine residue regulates BACE recycling back to the cell surface from early endosomes and enhances the interaction of BACE with GGA proteins in isolated protein assays. We found that BACE phosphorylation influences BACE-GGA interactions in cells using a new fluorescence-resonance-energy-transfer-based assay of protein proximity, fluorescence lifetime imaging. Although serine-phosphorylated BACE was distributed throughout the cell, interaction of GGA1 with the wild-type protein occurred in juxtanuclear compartments. Pseudo-phosphorylated and non-phosphorylated BACE mutants remained localized with GGA1 in the Golgi body, but the latter mutation diminished the two proteins' FRET signal. Because BACE phosphorylated at serine residues can be identified in human brain, these data suggest that serine phosphorylation of BACE is a physiologically relevant post-translational modification that regulates trafficking in the juxtanuclear compartment by interaction with GGA1.
GE Plastics Optimizes the Two-Echelon Global Fulfillment Network at Its High Performance Polymers Division
Authors: Tyagi Rajesh , Kalish Peter , Akbay Kunter , Munshaw Glenn
Published: October 2004

To achieve the highest customer satisfaction at the lowest costs, GE Plastics adopted a global approach to its manufacturing operations. Previously it met demand in one geographic region with production from that region only. It developed a decision-support system (DSS) to optimize the two-echelon global manufacturing supply chain for its high performance polymers division. The DSS uses a math-programming model to maximize contribution margin while taking into consideration product demands and prices, plant capacities, production costs, distribution costs, and raw material costs. The results of the model are the optimal production quantities by plant and the total contribution margin. The DSS is implemented in Excel and uses LINGO to solve the optimization model. After successfully implementing this system at the high performance polymers division, GE Plastics is rolling it out to other divisions.
Linking Product Variety to Order-Fulfillment Strategies
Authors: Pil Frits K. , Holweg Matthias
Published: October 2004

Providing a variety of attributes in products is an important way of attracting customers, but it often increases complexity and managerial cost. We drew on two data sets collected in the automotive sector to explore the link between external variety (the variety offered the customer) and internal variety (the variety involved in creating the product). We found that these two dimensions can be independent of each other. External variety is problematic for firms producing to forecast, and handling internal variety is challenging for firms building products to order. The effectiveness of strategies to mitigate variety's negative effects, such as modularity, mutability, late configuration, and option bundling, depends on the order-fulfillment strategy the firm follows.
Inventory Requirements Planning at Lucent Technologies
Authors: Bangash Alex , Bollapragada Ramesh , Klein Rachelle , Raman Narayan , Shulman Herbert B. , Smith Donald R.
Published: October 2004

The inventory requirements planning (IRP) system is a decision-support tool that Lucent has used to determine its buffering requirements for parts in a time-phased provisioning system. It measured the deviation of actual supply and demand from their planned values and, using the historical profile of these deviations, determined the safety-stock levels Lucent needed to meet the desired service levels. In doing so, it quantified the relationships among the inventory drivers: supply intervals, demand and supply variability, desired service levels, and part proliferation. It used these drivers to identify and drive initiatives to improve processes to reduce uncertainty in the provisioning process. Several Lucent locations have used the IRP system to realign inventories and to improve service in various manufacturing and distribution facilities. The IRP system's value has been recognized through several awards. It also contributed to Lucent's receiving the Malcolm Baldrige Award in 1992 (as a part of AT&T Corporation) and subsequently the INFORMS Prize in 1998.
An Integrated Planning System for Managing the Refurbishment of Thermoluminescent Badges
Authors: Bayiz Murat , Tang Christopher S.
Published: October 2004

ABC Worldwide Dosimetry Service provides a high-quality service for measuring and reporting radioactive exposure at its customers' sites. It leases thermoluminescent badges that record radioactive exposure over a prespecified time period. As each recording cycle ends, ABC must send refurbished (or new) badges to the customers before they return the old badges to ensure continuous monitoring. It then measures, recalibrates, and refurbishes the returned badges for future use. We developed an integrated system that could help ABC to manage its purchasing schedule for new badges so it can meet a target customer service level with minimal inventory. We ran our integrated system using the data ABC provided and found that our system could have helped ABC to reduce its inventory level by 17.7 percent and its costs by $820,000 within a six-month period.
Attitudes of Finnish Community Pharmacists Toward Concordance
Authors: Kansanaho Heli M , Puumalainen Inka I , Varunki Maaret M , Airaksinen Marja SA , Aslani Parisa
Published: October 2004

BACKGROUND

Concordance is a new model of interaction between healthcare professionals and patients. The work of pharmacists and patients in the consultation is a negotiation between equals, and the aim is therapeutic alliance between them.

OBJECTIVE

To assess Finnish community pharmacists’ attitudes toward concordance and its perceived impact on pharmacist–patient consultations during a 4-year Finnish project (TIPPA Project 2000–2003) aimed at promoting patient counseling.

METHODS

A survey of a random sample of 734 community pharmacists in Finland was conducted in 2002. The questionnaire included an attitudinal scale and 2 open-ended questions on the impact of the TIPPA Project on patient counseling. Attitudes toward concordance were measured using a modified version of the LATCon scale. The construct validity and internal consistency of the scale were evaluated using factor analysis and Cronbach's α. Mean summative factor scores (MSS) and 95% confidence intervals were calculated for each factor. The responses to the open-ended questions were content analyzed.

RESULTS

A response rate of 51% (n = 376) was obtained. Almost 80% of the respondents strongly agreed that the highest priority in patient counseling was to establish a therapeutic alliance between the pharmacist and patient. Factor analysis of the attitudinal scale yielded 3 primary factors explaining 37.6% of the variance, interpreted as respecting patients’ beliefs (α = 0.60; MSS = 1.90; 95% CI 2.25 to 2.40), establishing a therapeutic alliance (α = 0.65; MSS = 1.36; 95% CI 1.31 to 1.40), and sensitivity to patients’ reactions (α = 0.66; MSS = 2.33; 95% CI 1.83 to 1.96). Results of the open-ended questions indicated that the TIPPA Project had a positive impact on pharmacists’ attitudes toward concordance.

CONCLUSIONS

Respondents to our survey were supportive of concordance. The TIPPA Project elicited a positive impact on pharmacists’ attitudes toward counseling. Pharmacist education through programs such as TIPPA can aid in the implementation of a concordance-based counseling practice.
Mutational Analysis of Two Stefin A Epitopes
Authors: Kopitar-Jerala N. , Jerala R. , Turk B. , Gubensek F. , Turk V.
Published: October 2004

Stefin A, an intracellular inhibitor of cysteine proteinases, is expressed most abundantly in epithelial cells and in cells of lymphatic origin. In order to study its role in normal and pathological conditions we have prepared and characterized monoclonal antibodies against recombinant stefin A. Two high affinity monoclonal antibodies (mAbs) (A22 and C52) were tested for binding to free and papain-complexed stefin A and to a chimeric inhibitor, consisting of 61 amino acid residues of stefin A and 37 carboxy-terminal residues of stefin B. mAb A22 recognized not only free stefin A but also stefin A in complex with papain. The mAbs were further tested for their cross-reactivity against stefin A and B isolated from different mammalian species. On the basis of sequence similarity and tertiary structure of human stefin A we have prepared three mutants–Glu33Lys, Asp61Gly and Asn62Tyr–and their reactivity with the mAbs was tested. The binding affinities of mAb A22 for the Asp61Gly and Asn62Tyr mutants were significantly lower, indicating that the two amino acids are part of the stefin A epitope recognized by A22. The binding of both mAbs to the mutants Gly4Arg and Gly4Glu was comparable to wild-type stefin A.