bluuebunny/crossref_metadata_2025_split huggingface dataset:
Game theoretic approach to multiobjective designs: Focus on inherent safety
Authors: Meel Anjana , Seider Warren D. , Soroush Masoud 
Published: September 2005

AbstractA method for designing processes that are inherently safer—with the primary focus on disturbances having the potential for unbounded hazardous responses—is introduced. In cases where safety is not threatened (as in isothermal fermentation reactors), but product quality can rapidly degrade, this method provides designs that ensure high product quality (as in pharmaceutical processes). Using game theory, the method accounts for the trade‐offs in profitability, controllability, safety and/or product quality, and flexibility. For nonlinear processes that are hard to control; that is, have an unstable and/or nonminimum‐phase steady state, over a wide range of operating conditions, extended bifurcation diagrams are introduced. When a steady state is nonminimum phase, the process may exhibit inverse response. The steady states of processes are classified on the basis of instability and nonminimum‐phase behavior to segregate the operating regimes into distinct zones. Locally optimal designs, one corresponding to each zone, are obtained first. These are compared with other locally optimal designs at alternate operating conditions, and/or process reconfigurations, to obtain the globally optimal design using game theory. Four indices—profitability, controllability, safety and/or product quality, and flexibility—characterize the optimality of a design. A novel index for safe operation and/or product quality at a steady state is formulated as a function of the eigenvalues of the Jacobian of the process model and the Jacobian of the process zero dynamics, providing a quantitative measure of instability and nonminimum‐phase behavior. The application of the proposed method to an isothermal, continuous stirred‐tank reactor (CSTR) with van der Vusse reactions, an exothermic CSTR, and an anaerobic fermentor with substrate and product inhibition is presented. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Thermally stratified liquid turbulence with a chemical reaction
Authors: Onishi Ryo , Komori Satoru 
Published: September 2005

AbstractEffects of stable and unstable thermal stratifications on turbulent mixing and chemical reaction in liquid turbulence were investigated by both laboratory experiments and numerical simulations. Instantaneous velocity and concentration were simultaneously measured using a combined technique with a two‐component laser‐Doppler velocimeter (LDV) and a laser‐induced fluorescence (LIF) method in two kinds of thermally stratified turbulent reacting flows: grid‐generated turbulence and a mixing layer. The results show that turbulent mixing in the fully developed liquid turbulence is affected mainly at large scales by buoyancy. However, the maximum value of the mean concentration of chemical product is independent of thermal stratification. In addition, a large‐eddy simulation (LES) based on a β‐pdf model was applied to the same thermally stratified reacting liquid flows as used in the experiments. The numerical results show that the stratification effects on the turbulent mixing and chemical reaction can be well predicted by the LES and the buoyancy effects are not significant in the subgrid‐scale models for the LES. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Variable hypomethylation of D4Z4 in facioscapulohumeral muscular dystrophy
Authors: Van Overveld Petra G. M. , Enthoven Leo , Ricci Enzo , Rossi Monica , Felicetti Luciano , Jeanpierre Marc , Winokur Sara T. , Frants Rune R. , Padberg George W. , Van Der Maarel Silvère M. 
Published: September 2005

AbstractFacioscapulohumeral muscular dystrophy (FSHD) progressively affects the facial, shoulder, and upper arm muscles and is associated with contractions of the polymorphic D4Z4 repeat array in 4q35. Recently, we demonstrated that FSHD alleles are hypomethylated at D4Z4. To study potential relationships between D4Z4 hypomethylation and both residual repeat size and clinical severity, we compared the clinical severity score with D4Z4 methylation in unrelated FSHD patients. Correcting the clinical severity score for age at examination improves the parameter to define clinical severity and provides further support for hypomethylation of FSHD alleles. However, a linear relationship between repeat size and clinical severity of the disease cannot be established. Interestingly, FSHD can be separated in two clinical severity classes: patients with residual repeat sizes of 10 to 20kb are severely affected and show pronounced D4Z4 hypomethylation. In contrast, patients with repeat sizes of 20 to 31kb show large interindividual variation in clinical severity and D4Z4 hypomethylation. Because the majority of familial FSHD cases are represented in this interval and considering the overt variation in clinical severity in these familial cases, it thus is imperative to develop comprehensive allele‐specific assays monitoring total D4Z4 methylation to investigate whether interindividual variation in D4Z4 methylation can be translated into a prognostic factor for clinical severity. Ann Neurol 2005;58:569–576
Novel threadlike structures (Bonghan ducts) inside lymphatic vessels of rabbits visualized with a Janus Green B staining method
Authors: Lee Byung‐Cheon , Yoo Jung Sun , Baik Ku Youn , Kim Ki Woo , Soh Kwang‐Sup 
Published: September 2005

AbstractA staining method has been developed for in situ and in vivo observation of a threadlike tissue afloat inside the lymphatic vessels of rabbits without adherence to the vessel wall. The existence of this novel structure was not noticed previously because it is extremely difficult to detect it by microscopic inspection of lymphatic vessels. We have found a method that utilizes Janus Green B (JGB), which stained heavily the novel structure. The tissue was studied by confocal laser scanning microscopy (CLSM), light microscopy, and cryoscanning electron microscopy (cryo‐SEM). The CLSM image obtained by acridine orange staining of the novel tissue revealed its characteristic nuclei distribution: rod‐shaped nuclei of 10–20 μm length aligned in a broken‐line/striped fashion. Hematoxylin and eosin staining revealed the threadlike structure passing through a lymphatic valve as histologically distinct from lymphatic vessels and valves. The cryo‐SEM image showed the threadlike structure inside a collapsed lymphatic vessel. There were spherical globular structures observable inside sinuses in a rapidly frozen sample, which suggests liquid flowing through the longitudinal ductules in the threadlike structure. The specific staining of the JGB suggests that these threadlike structures inside lymphatic vessels have a high density of mitochondria in their cells and/or nerve‐like properties, either of which may provide important clues to their physiological function. Anat Rec (Part B: New Anat) 286B:1–7, 2005. © 2005 Wiley‐Liss, Inc.
Characterization of mixing in a novel wavy‐walled bioreactor for tissue engineering
Authors: Bilgen Bahar , Chang‐Mateu I. Midey , Barabino Gilda A. 
Published: September 2005

AbstractThe wavy‐walled bioreactor (WWB) possesses a novel geometry comprised of walls with sinusoidal waves that mimic baffles in an effort to promote mixing. This geometry provides a unique hydrodynamic environment suitable for the cultivation of mammalian cells and tissues and the investigation of fluid mechanical effects on cell and tissue growth and development. In the present study, mixing in WWB was characterized and compared to that in a conventional spinner flask (SF). The key parameters included in this characterization were mixing time, residence time distribution (RTD), and dissolved oxygen concentration during engineered cartilage tissue cultivation. Factors that influenced mixing in WWB included wave amplitude, agitation rate, and the ratio of the impeller diameter to the tank diameter (D/T). Data obtained from RTD and acid base neutralization studies confirmed the presence of different mixing zones in WWB. A theoretical comparison of WWB to a baffled spinner flask (BSF) using computational fluid dynamics (CFD) modeling predicted that while enhanced mixing was achieved in wavy‐walled and BSF bioreactors, the shear stresses applied on tissue constructs were 15% lower in WWB. Improved mixing was achieved in WWB compared to the SF at similar D/T ratios, verified by improved oxygen transport and increased dispersion. However, for lower D/T ratios mixing in WWB was not necessarily improved. This study demonstrated the importance of characterization of mixing by showing the impact of even minor changes in bioreactor geometry and operating conditions. © 2005 Wiley Periodicals, Inc.
Randomized clinical trial of vertical or transverse laparotomy for abdominal aortic aneurysm repair
Authors: Fassiadis N , Roidl M , Hennig M , South L M , Andrews S M 
Published: September 2005

AbstractBackgroundThe objective of this randomized trial was to evaluate the incidence of incisional hernia after transverse or vertical incisions for open aortic aneurysm repair.MethodsThe study group comprised 69 patients who underwent elective aneurysm repair between November 1998 and November 2000 (60 men, nine women; mean age 72·8 (range 56–95) years). Patients were randomized to a transverse (n = 32) or vertical (n = 37) incision for the procedure. Of the 42 patients who were still alive in February 2004, 37 (15 transverse, 22 vertical incisions) attended for review. Laparotomy scars were assessed both clinically and ultrasonographically by the same examiner, to look for incisional hernia.ResultsMean follow-up was 4·4 years. A multivariable logistic regression analysis revealed that the type of incision was the only parameter that significantly influenced the rate of incisional hernia: six of 15 patients with a transverse laparotomy versus 20 of 22 with a vertical laparotomy (P = 0·010).ConclusionThe incidence of incisional hernia was high after aortic aneurysm repair, but was lower in patients who had a transverse incision.
Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery
Authors: Agnelli G , Bergqvist D , Cohen A T , Gallus A S , Gent M 
Published: September 2005

Abstract

Background
The aim of this study was to assess whether the synthetic factor Xa inhibitor fondaparinux reduced the risk of venous thromboembolism more efficiently than the low molecular weight heparin dalteparin in patients undergoing major abdominal surgery.

Methods
In a double-blind double-dummy randomized study, patients scheduled for major abdominal surgery under general anaesthesia received once-daily subcutaneous injections of fondaparinux 2·5 mg or dalteparin 5000 units for 5–9 days. Fondaparinux was started 6 h after surgery. The first two doses of dalteparin, 2500 units each, were given 2 h before surgery and 12 h after the preoperative administration. The primary outcome measure was a composite of deep vein thrombosis detected by bilateral venography and symptomatic, confirmed deep vein thrombosis or pulmonary embolism up until day 10. The main safety outcome measure was major bleeding during treatment.

Results
Among 2048 patients evaluable for efficacy, the rate of venous thromboembolism was 4·6 per cent (47 of 1027) with fondaparinux compared with 6·1 per cent (62 of 1021) with dalteparin, a relative risk reduction of 24·6 (95 per cent confidence interval −9·0 to 47·9) per cent (P = 0·144), which met the predetermined criterion for non-inferiority of fondaparinux. Major bleeding was observed in 49 (3·4 per cent) of 1433 patients given fondaparinux and 34 (2·4 per cent) of 1425 given dalteparin (P = 0·122).

Conclusion
Postoperative fondaparinux was at least as effective as perioperative dalteparin in patients undergoing high-risk abdominal surgery.
Nanostructured Ordering of Fluorescent Markers and Single Proteins on Substrates
Authors: Groll Juergen , Albrecht Krystyna , Gasteier Peter , Riethmueller Silke , Ziener Ulrich , Moeller Martin 
Published: September 2005

AbstractHighly ordered hexagonal nanopatterns of gold clusters on glass substrates were used as anchoring points for the specifc attachment of fluorescence dyes and proteins labeled with fluorescence dyes. Thiol‐ or disulfide‐containing linker molecules were used for the binding to the gold dots. In order to ensure specific binding on the gold dots only, the surface area in between the dots was protected against unspecific adsorption. For the attachment of polar low‐molecular‐weight fluorescence dyes, an octadecyltrichlorosilane self‐assembled monolayer was prepared on the surface in between the gold dots, whereas a layer prepared from star‐shaped poly(ethylene oxide‐stat‐propylene oxide) prepolymers was used to prevent unspecific adsorption of proteins between the gold dots. Fluorescence microscopy proved the specific binding of the dyes as well as of the proteins. Scanning force microscopy studies show that each gold dot is only capable of binding one protein at a time.
An Experimental and Molecular‐Modeling Study of the Binding of Linked Sulfated Tetracyclitols to FGF‐1 and FGF‐2
Authors: Cochran Siska , Li Cai Ping , Bytheway Ian 
Published: September 2005

AbstractThe experimental binding affinities of a series of linked sulfated tetracyclitols [Cyc2N‐R‐NCyc2, where Cyc=C6H6(OSO3Na)3 and R=(CH2)n (n=2–10), p‐xylyl or (C2H4)2‐Ncyc] for the fibroblast growth factors FGF‐1 and FGF‐2 have been measured by using a surface plasmon resonance assay. The KD values range from 7.0 nM to 1.1 μM for the alkyl‐linked ligands. The binding affinity is independent of the flexibility of the linker, as replacement of the alkyl linker with a rigid p‐xylyl group did not affect the KD. Calculations suggest that binding modes for the p‐xylyl‐linked ligand are similar to those calculated for the flexible alkyl‐linked tetracyclitols. The possible formation of cross‐linked FGF:cyclitol complexes was examined by determining KD values at increasing protein concentrations. No changes in KD were observed; this suggesting that only 1:1 complexes are formed under these assay conditions. Monte Carlo multiple‐minima calculations of low‐energy conformers of the FGF‐bound ligands showed that all of the sulfated tetracyclitol ligands can bind effectively in the heparan sulfate‐binding sites of FGF‐1 and FGF‐2. Binding affinities of these complexes were estimated by the Linear Interaction Energy (LIE) method to within a root‐mean‐square deviation of 1 kcal mol−1 of the observed values. The effect of incorporating cations to balance the overall charge of the complexes during the LIE calculations was also explored.
A Formal Total Synthesis of Eleutherobin Using the Ring‐Closing Metathesis (RCM) Reaction of a Densely Functionalized Diene as the Key Step: Investigation of the Unusual Kinetically Controlled RCM Stereochemistry
Authors: Castoldi Damiano , Caggiano Lorenzo , Panigada Laura , Sharon Ofer , Costa Anna M. , Gennari Cesare 
Published: September 2005

AbstractAsymmetric oxyallylation reactions and ring‐closing metathesis have been used to synthesize compound 3, a key advanced intermediate used in the total synthesis of eleutherobin reported by Danishefsky and co‐workers. The aldehyde 6, which is readily prepared from commercially available R‐(−)‐carvone in six steps in 30 % overall yield on multigram quantities, was converted into the diene 5 utilizing two stereoselective titanium‐mediated Hafner–Duthaler oxyallylation reactions. The reactions gave the desired products (8 and 12) in high yields (73 and 83 %, respectively) as single diastereoisomers, with the allylic alcohol already protected as the p‐methoxyphenyl (PMP) ether, which previous work has demonstrated actually aids ring‐closing metathesis compared to other protective groups and the corresponding free alcohol. Cyclization under forcing conditions, using Grubbs' second‐generation catalyst 13, gave the ten‐membered carbocycle (E)‐14 in 64 % yield. This result is in sharp contrast to similar, but less functionalized, dienes, which have all undergone cyclization to give the Z stereoisomers exclusively. A detailed investigation of this unusual cyclization stereochemistry by computational methods has shown that the E isomer of the ten‐membered carbocycle is indeed less thermodynamically stable than the corresponding Z isomer. In fact, the selectivity is believed to be due to the dense functionality around the ruthenacyclobutane intermediate that favors the trans‐ruthenacycle, which ultimately leads to the less stable E isomer of the ten‐membered carbocycle under kinetic control. During the final synthetic manipulations the double bond of enedione (E)‐16 isomerized to the more thermodynamically stable enedione (Z)‐4, giving access to the advanced key‐intermediate 3, which was spectroscopically and analytically identical to the data reported by Danishefsky and co‐workers, and thereby completing the formal synthesis of eleutherobin.
Aberrant methylation of H‐cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma
Authors: Seuk Kim Jin , Han Joungho , Shim Young Mog , Park Joobae , Kim Duk‐Hwan 
Published: September 2005

AbstractBACKGROUNDAbnormalities in the H‐cadherin gene have been reported in several human malignancies, including nonsmall cell lung carcinoma (NSCLC). Aberrant methylation of the H‐cadherin promoter also has been reported in NSCLC, but its clinical significance remains to be elucidated.METHODSThe authors studied H‐cadherin methylation in 305 patients with NSCLC to gain a further understanding of the clinicopathologic and prognostic significance of H‐cadherin methylation in patients with NSCLC. The methylation status of the H‐cadherin gene was investigated by using methylation‐specific polymerase chain reaction analysis in paraffin blocks from 305 patients with NSCLC. Ki‐67 expression was assessed by immunohistochemical staining. All statistical analyses were 2‐sided with a 5% Type I error rate.RESULTSH‐cadherin methylation was observed in 130 of 305 tumor samples (43%). The prevalence of H‐cadherin methylation was associated significantly with pathologic stage and was observed in 44% of patients with Stage I disease, in 23% of patients with Stage II disease, in 59% of patients with Stage III, and in 88% of patients with Stage IV disease (P = 0.001). H‐cadherin methylation occurred with a 2.71 times greater prevalence (95% confidence interval [95% CI], 1.21–6.09; P = 0.01) T2 tumors than in T1 tumors and with a 3.78‐fold greater prevalence (95% CI, 1.05–13.59; P = 0.04) in T3 tumors than in T1 tumors. However, lymph node metastasis was related inversely with H‐cadherin methylation (odds ratio = 0.51; 95% CI, 0.28–0.95; P = 0.03), and H‐cadherin methylation was not associated with the Ki‐67 labeling index (P = 0.53) or with tumor size (P = 0.89). No relation was found between H‐cadherin methylation and survival in patients with Stage I NSCLC (P = 0.51) or in patients with Stage II NSCLC (P = 0.46).CONCLUSIONSThe current findings suggested an association between H‐cadherin methylation and tumor progression in NSCLC but had no prognostic significance in patients with early‐stage NSCLC. In addition, H‐cadherin methylation may be a valuable candidate molecular marker for the early detection of NSCLC. Cancer 2005. © 2005 American Cancer Society.
Morphological changes in the Royal College of Surgeons rat retina during photoreceptor degeneration and after cell‐based therapy
Authors: Wang Shaomei , Lu Bin , Lund Raymond D. 
Published: September 2005

AbstractThere are concomitant morphological and functional changes in the inner retina during the course of photoreceptor degeneration in a range of animal models of retina degeneration and in humans with eye disease. One concern that has been raised is that the changes occurring in the inner retina might compromise attempts to rescue or restore visual input by various interventional approaches. It is known that cell‐based therapy can preserve significant visual capability for many months. In this study, we examine the overall changes in the Royal College of Surgeons (RCS) rat during degeneration and the effects of cell transplantation by means of immunohistochemistry and confocal microscopy. The degenerative changes are complex, and they progress with age. They involve the neurons with which both rods and cones interconnect—retinal second‐ and third‐order neurons underwent dramatic modification, including sprouting, retraction as photoreceptor loss progressed—as well as Müller glia and secondary vascular changes, which were associated at later times with neuronal migration. The pathological vascular changes led to major disruption of inner retina. After introducing a retinal pigment epithelial cell line to the subretinal space early in the progress of photoreceptor degeneration, most inner retinal changes were held in abeyance for up to at least 10 months of age. Given the concern that has been raised regarding whether inner retinal changes might compromise any graft‐related benefit, this is an encouraging finding. J. Comp. Neurol. 491:400–417, 2005. © 2005 Wiley‐Liss, Inc.
Branching patterns of parabrachial neurons projecting to the central extended amgydala: Single axonal reconstructions
Authors: Sarhan Maysa , Freund‐Mercier Marie‐Jose , Veinante Pierre 
Published: September 2005

AbstractElectrophysiological evidence suggests that the spinoparabrachioamygdaloid pathway carries nociceptive information that may be important for the elaboration of physiological and emotional responses to noxious events. The pontine parabrachial nucleus (pPB) sends a massive projection to the central nucleus of the amygdala (CeA) and lateral bed nucleus of the stria terminalis (BSTL), both regions belonging to a broader macrostructure, the central extended amygdala (EAc). The aim of this study was to examine whether different EAc components are targeted by a same pPB neuron, by reconstructing single axonal branching patterns after anterograde labelling. Small deposits of biotinylated dextran amine in the region of the external lateral pPB result in dense and specific labelling in the whole EAc. Reconstructed axons innervate either the lateral or the capsular part of the CeA with perisomatic or bushy terminals, respectively. A subset of axons enters the stria terminalis rostrally to follow its trajectory caudally toward the CeA. Individual axons targeting the CeA usually send collaterals to other EAc components, especially those projecting to the lateral CeA, which often coinnervate the BSTL. By contrast, only few branches were found outside the EAc. These results suggest that the noxious information travelling from the pPB to the CeA may also be transmitted to other EAc components. This pPB‐EAc pathway, which appears distinct from the parabrachiohypothalamic and parabrachiothalamic projections, would be the anatomical basis through which the EAc elaborates the autonomic, endocrine, and emotional components of pain. J. Comp. Neurol. 491:418–442, 2005. © 2005 Wiley‐Liss, Inc.