bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered processing of thawed red cells to improve the in vitro quality during postthaw storage at 4°C
Authors: Lagerberg Johan W.M. , Truijens‐de Lange Rosa , De Korte Dirk , Verhoeven Arthur J.
Published: August 2007

BACKGROUND: The use of a functionally closed system (ACP215, Haemonetics) for the glycerolization and deglycerolization of red blood cell (RBC) units allows for prolonged postthaw storage. In this study, the postthaw quality of previously frozen, deglycerolized RBCs resuspended in saline‐adenine‐glucose‐mannitol (SAGM) or additive solution AS‐3 was investigated.

STUDY DESIGN AND METHODS: Leukoreduced RBC units were frozen with 40 percent glycerol and stored at −80°C for at least 14 days. The thawed units were deglycerolized with the ACP215, resuspended in SAGM or AS‐3, and stored at 2 to 6°C for up to 21 days.

RESULTS: The mean ± standard deviation in vitro freeze‐thaw‐wash recovery was 81 ± 5 percent. During storage, hemolysis of deglycerolized cells remained below 0.8 percent for 2 days in SAGM and for 14 days in AS‐3. This difference was explained by the protective effect of citrate, which is present in AS‐3. Cells stored in AS‐3 showed a lower glycolytic activity and a faster decline in adenosine 5′‐triphosphate (ATP) than cells in SAGM. Increasing the internal pH of cells before storage in AS‐3 by use of phosphate‐buffered saline (PBS) in the deglycerolization procedure resulted in elevated lactate production and better maintenance of intracellular ATP content. After 3 weeks of storage, the ATP content of PBS‐washed cells amounted to 2.5 ± 0.5 µmol per g of hemoglobin (Hb), whereas for saline/glucose‐washed cells this value was decreased to 1.0 ± 0.3 µmol per g of Hb.

CONCLUSIONS: Leukoreduced, deglycerolized RBCs can be stored for 48 hours in SAGM. Improved ATP levels during refrigerated storage can be observed with thawed cells, resuspended in AS‐3, when PBS is used as a washing solution.
Translation of glycoprotein IIIa in stored blood platelets
Authors: Thon Jonathan N. , Devine Dana V.
Published: August 2007

BACKGROUND: Platelet (PLT) products have a short shelf life (5 days) owing in part to the deterioration of the quality of PLTs stored at 22°C. This creates significant inventory challenges, and blood banks may suffer shortages and high wastage as a result. The precise biochemical pathways involved in the PLT storage lesion are unknown and must be understood before storage time can be extended.

STUDY DESIGN AND METHODS: Informed by previous proteomics analysis, specific PLT glycoprotein (GP) concentration and surface expression were examined by Western blot and flow cytometry. mRNA concentration was determined by Northern blot and real‐time polymerase chain reaction. Protein synthesis was confirmed by [35S]methionine labeling.

RESULTS: Western blots of GPIIIa revealed a twofold increase in concentration on Day 7 of storage and a fourfold increase on Day 10. By flow cytometry, surface expression of the GPIIb/IIIa increased by 13.4 percent on Day 7 and 41.9 percent on Day 10. Full‐length GPIIIa mRNA was present throughout this storage period and was shown to have a half‐life of approximately 2.9 days. Translation of GPIIb and IIIa during storage was confirmed by [35S]methionine labeling.

CONCLUSION: This article confirms that PLTs are capable of synthesizing biologically relevant proteins ex vivo throughout a 10‐day storage period with particularly long‐lived mRNA and provides a framework through which the biochemical mechanisms involved in the translational regulation of proteins thought to be involved in the initiation or exacerbation of the PLT storage lesion can be investigated.
Impact of Different Pacing Modes on Left Ventricular Contractility Following Cardiopulmonary Bypass
Authors: BAKHTIARY FARHAD , DOGAN SELAMI , DZEMALI OMER , ACKERMANN HANNS , KLEINE PETER , SCHÄCHINGER VOLKER , MORITZ ANTON , AYBEK TAYFUN
Published: August 2007

Background: Acute left ventricular (LV) dysfunction after cardiopulmonary bypass (CBP) is a serious complication in cardiac surgery. The aim of this study was to investigate the effect of different epicardial pacing modes on LV contractility and changes of myocardial oxygen extraction (MVO2) following CPB in an animal model. The utility of conductance catheter measurement versus left ventricular outflow tract mean systolic acceleration (LVOTAcc) for quantification of LV function was evaluated.

Methods: Fourteen piglets underwent median sternotomy and CPB for 90 minutes, myocardial ischemia for 60 minutes, and reperfusion for 30 minutes. Different pacing modes were obtained before and after CPB to investigate changes in LV function. LV Function was quantified by end‐systolic‐pressure‐volume relationships (ESPVR) as measured by the conductance catheter method and by LVOTAcc obtained from transepicardial echocardiographic studies.

Results: LV contractility improved significantly by biventricular and atrial pacing compared with natural sinus rhythm (SR). MVO2 remained stable or even decreased with biventricular pacing after surgery compared with SR. Right ventricular pacing resulted in poor LV‐function with a rise of MVO2. LVOTAcc showed a strong correlation to invasively measured ESPVR.

Conclusion: Postoperative biventricular pacing was associated with an improved LV contractility without rise of MVO2 compared with SR and atrial pacing. At termination of CPB, this appears to facilitate the management of LV failure and potentially may reduce the need for inotropic support, additionally protecting myocardial metabolism.

The echocardiographic assessment of LVOTAcc was a simple and reliable as well as effective method to quantify LV contractility and showed a good correlation with the more invasive conductance catheter.
Hemodynamic Collapse During Left Ventricular Lead Implantation
Authors: PUNNAM SUJEETH R , HOLIDAY JEFFREY , JANES RENEE , TOUMA RABIH , LI HAIYAN , PATEL MEHUL , ABELA GEORGE S , THAKUR RANJAN K
Published: August 2007

Hypotension as a procedural complication during cardiac resynchronization therapy (CRT) implantation was reported in the initial randomized clinical trials. However, this phenomenon is not well characterized. We reviewed our CRT implantation experience to better understand this issue. There were 105 patients who underwent left ventricular lead implantation for CRT. Four patients had marked hypotension (systolic blood pressure ≤ 50 mmHg) during the procedure. All had a history of hypertension and diabetes mellitus and were pacemaker dependent. Two had normal renal function, one had moderate renal insufficiency, and one was on dialysis. Three patients had ischemic cardiomyopathy. All had left ventricular ejection fraction ≤20% and were in New York Heart Association class III. Propofol and midazolam were used for sedation as standard protocol. Two patients had sudden hypotension when the coronary sinus was being cannulated, and two patients experienced sudden hypotension during left ventricular pacing. Cardiac tamponade as a possible cause was ruled out by echocardiography. We discuss possible mechanisms of sudden hemodynamic collapse during CRT implantation.
An Approach to “Ablate and Pace”:AV Junction Ablation and Pacemaker Implantation Performed Concurrently from the Same Venous Access Site
Authors: ISSA ZIAD F.
Published: August 2007

Background: Atrioventricular junction (AVJ) ablation combined with permanent pacemaker implantation (the “ablate and pace” approach) remains an acceptable alternative treatment strategy for symptomatic, drug‐refractory atrial fibrillation (AF) with rapid ventricular response. This case series describes the feasibility and safety of catheter ablation of the AVJ via a superior vena caval approach performed during concurrent dual‐chamber pacemaker implantation.

Methods: A total of 17 consecutive patients with symptomatic, drug‐refractory, paroxysmal AF underwent combined AVJ ablation and dual‐chamber pacemaker implantation procedure using a left axillary venous approach. Two separate introducer sheaths were placed into the axillary vein. The first sheath was used for implantation of the pacemaker ventricular lead, which was then connected to the pulse generator. Subsequently, a standard ablation catheter was introduced through the second axillary venous sheath and used for radiofrequency (RF) ablation of the AVJ. After successful ablation, the catheter was withdrawn and the pacemaker atrial lead was advanced through that same sheath and implanted in the right atrium.

Results: Catheter ablation of the AVJ was successfully achieved in all patients. The median number of RF applications required to achieve complete AV block was three (range 1–10). In one patient, AV conduction recovered within the first hour after completion of the procedure, and AVJ ablation was then performed using the conventional femoral venous approach. There were no procedural complications.

Conclusion: Catheter ablation of the AVJ can be performed successfully and safely via a superior vena caval approach in patients undergoing concurrent dual‐chamber pacemaker implantation.
Effect of Dl‐Sotalol on Mortality and Recurrence of Ventricular Tachyarrhythmias:Ischemic Compared to Nonischemic Cardiomyopathy
Authors: FURUSHIMA HIROSHI , CHINUSHI MASAOMI , OKAMURA KAZUKI , KOMURA SATORU , TANABE YASUTAKA , SATO AKINORI , IZUMI DAISUKE , AIZAWA YOSHIFUSA
Published: August 2007

Objective:

We compared the effectiveness of sotalol on mortality and the recurrence of ventricular tachyarrhythmia (VTA) between idiopathic dilated cardiomyopathy (IDCM) and coronary artery disease (CAD).

Patients:

Forty patients with spontaneous VTA and induced VTA associated with CAD (n = 23) and IDCM (n = 17) were studied. In all patients, sotalol was prescribed and an electrophysiologic study (EPS) was performed to evaluate its effect on the induction of VTA. There were no significant differences in left ventricular ejection fraction (LVEF) between CAD and IDCM (35%± 10% vs. 35%± 12%),

Results:

After sotalol, there were no significant differences in the QTc interval on electrocardiogram (ECG) or in the effective refractory period in the apex of the right ventricle between the two groups, but sotalol was more effective in preventing the induction of VTA in CAD than in IDCM (65% vs. 29%; P < 0.05). During a mean follow‐up period of 47 ± 27 months, the overall VTA recurrence rate was significantly lower in CAD than in IDCM (P < 0.01). The all‐cause mortality rate tended to be lower in CAD than in IDCM, but the difference was not significant (P = 0.07). Electrical storm (ES) occurred more frequently in IDCM than in CAD, (41% vs. 13%; P < 0.05), and all patients with ES (n = 10) failed to respond to sotalol as assessed by EPS.

Conclusion:

Sotalol reduced the overall VTA recurrence rate and all‐cause mortality more in CAD than in IDCM.
Unexpected, Dramatic Improvement in Atrioventricular Conduction During Pacemaker Implantation for Apparent Complete Heart Block
Authors: DIZON JOSE' , WANG HUIJIAN , BIVIANO ANGELO , GARAN HASAN
Published: August 2007

We describe the case of a 29‐year‐old man with complete heart block after aortic and mitral valve surgery for bacterial endocarditis. Prior to pacemaker implantation, the patient had sinus bradycardia with third degree atrioventricular (AV) block. During testing of the atrial lead, the patient manifested intact AV conduction with a constant PR interval, which was robust up to 120 beats/min. This case represents a dramatic example of unexpected, improved AV conduction, perhaps a result of loss of Phase IV block.
Cardiac Memory Induced by QRS Widening due to Propafenone Toxicity
Authors: WYLIE JOHN V. , ZIMETBAUM PETER , JOSEPHSON MARK E. , SHVILKIN ALEXEI
Published: August 2007

Propafenone toxicity can cause significant QRS widening and markedly abnormal ventricular activation pattern. Aberrant ventricular activation upon its resolution is known to produce persistent T‐wave changes known as “cardiac memory” (CM). A 74‐year‐old woman presented with a severely abnormal electrocardiogram consistent with propafenone toxicity. As her QRS complex narrowed, T‐wave inversions developed with the T‐wave axis and resolution kinetics consistent with CM. Abnormal ventricular activation due to propafenone toxicity can result in CM development.
Reverse Remodeling with Resynchronization in an Asymptomatic Patient with Dilated Hypokinetic Cardiomyopathy
Authors: D'IVERNOIS CHRISTOPHE , DELUCHE LAURENT , TUAN NGUYEN LE ANH , BLANC PATRICK
Published: August 2007

Cardiac resynchronization therapy (CRT) is a validated treatment for selected heart failure patients who remain highly symptomatic despite optimal drug treatment. Yet there is currently no indication for CRT in patients with few or no symptoms. We report a spectacular “reverse remodeling” effect after CRT in an asymptomatic patient with hypokinetic dilated myocardiopathy who needed pacing for atrio‐ventricular conduction disorder. CRT was chosen to prevent deterioration of left ventricular function by conventional right apical pacing. Thus, CRT could be indicated in patients with hypokinetic dilated myocardiopathy before the appearance of symptoms.
A Case of Persistent Atrial Fibrillation Cured by Focal Ablation in a Young Patient
Authors: NAKAHARA SHIRO , TAKAYANAGI KAN , IESAKA YOSHITO
Published: August 2007

We present a case of a 25‐year‐old man who had persistent atrial fibrillation (AF) lasting for three months. The persistent AF was terminated by a 20‐mg bolus infusion of adenosine triphosphate. Frequent and repetitive episodes of ectopic atrial tachycardia (EAT) emerged from the mid‐portion of the saddle between the left superior and inferior pulmonary veins. The successful ablation was achieved by a focal ablation at the site with the earliest activation preceding the P‐wave onset by 42 ms, and exhibited a QS pattern in the unipolar recording. This is rare case in which focal ablation could cure persistent AF.
In vitro activity of daptomycin and tigecycline against coagulase‐negative staphylococcus blood isolates from bone marrow transplant recipients
Authors: Kratzer Christina , Rabitsch Werner , Hirschl Alexander M. , Graninger Wolfgang , Presterl Elisabeth
Published: August 2007

Background and objective:  Multi‐resistant coagulase‐negative staphylococci (CNS) may cause systemic infections in patients undergoing bone marrow transplantation. Daptomycin, a new lipopeptide, and tigecycline, a new glycylcycline, have excellent activity against Gram‐positive bacteria including methicillin‐resistant staphylococci. This study presents the in vitro activity of daptomycin and tigecycline compared to vancomycin and fosfomycin against 105 CNS isolated from 76 bone marrow transplant patients with symptomatic bacteremia.

Material and methods:  Blood stream isolates of Staphylococcus epidermidis (n = 102) and Staphylococcus haemolyticus (n = 3) from bone marrow transplant patients were collected from 2000 to 2006. The susceptibility of all isolates was tested using methods of the Clinical Laboratory Standards Institute.

Results:  The minimal inhibitory concentrations MIC50 and MIC90 were 0.125 μg/mL and 0.25 μg/mL for daptomycin, 0.25 and 0.5 μg/mL for tigecycline, 1 μg/mL and 2 μg/mL for vancomycin, and 8 μg/mL and >256 μg/mL for fosfomycin, respectively. MIC values of tested agents were similar for both methicillin‐sensitive and methicillin‐resistant S. epidermidis strains.

Conclusions:  All CNS isolates were susceptible to the new antistaphylococcal agents daptomycin and tigecycline. Although vancomycin had been used over the past 30 yr at our bone marrow transplant unit all CNS were still susceptible to vancomycin.
Adventures in a Strange Paradise ‐ Utopia in “Nicolai Klimii Iter subterraneum”*
Authors: Jones James F.
Published: August 2007

Ludvig Holberg's Niels Klim provides an example of a text in which a therne common to eighteenth‐century Europe ‐ the utopian vision ‐ intersects with a literary convention common to Western letters ‐ the descent to the world below through a cave. Originally written in Latin in order that it be read throughout Europe, the book contains several aspects characteristic of the Zeitgeist of eighteenth‐century philosophical and literary thought while, at the same time, its treatment of the utopian theme may well point to a possible standard by which the synoptic depictions of utopia may be distinguished from those belonging to the much larger number of more traditional utopian texts written in a century that was to a great degree obsessed with the notion of creating a perfect society.
The Utopian Dimension of Kafka's “In The Penal Colony”
Authors: Hadomi Leah
Published: August 2007

“In the Penal Colony” incorporates the dilemma of Utopia expressed in a continuum from the Utopian spiritual longing to its material Dystopian realization and the Anti‐Utopian attempt to retreat from it. The spatial and temporal background of the story is portrayed as a movement from centrality and timelessness (Utopian) to peripherness and sequential time (Dystopian and Anti‐Utopian). The spiritually closed, homogeneous, and coherent Utopian world of the Old Commandant turns into Dystopian nightmare while being implemented by the machine and leads to a retreat to the Anti‐Utopian world of the colony.

The “stranger,” the “guide” and the “common member,” representative figures of the Utopian genre, are projected into a Kafkaesque world as characterised by the stranger, explorer, officer, condemned man and soldier. Kafka's unique clustering of figures emphasises the Utopian dilemma. A feeling of anguish is expressed in the description of three meaningful moments of “silence,” placed at significant points within the structure and expressing the experience of “… guilt (that) is never to be doubted” in the Penal Colony.
Nullpunkt und kein Ende? Perspectives and Theses on Postwar German Literature
Authors: Roberts David
Published: August 2007

It is now thirty five years since the end of the Second World War. The immediate postwar period has begun to acquire the historical dimensions which open up new perspectives on German literature “after the apocalypse.” A crucial question in the current literaryhistorical debate is the evaluation of 1945. Was it the drastic break with the catastrophic legacy of the past, the situation of “tabula rasa” that contemporaries felt it to be, or no more than the illusion of a new beginning? In the process of seeking continuities rather than discontinuities a new picture of German literature since the Weimar Republic is beginning to emerge. The new position represented by Trommler and Schäfer places the “caesura” of 1945 in the context of the one literary epoch from the end of the 1920's to the end of the 1950's. The present article is an attempt to relate this debate to the wider question of the periodisation of German literature of this century and to argue that the literary and ideological continuities posited by Trommler and Schafer and the global turning point of 1945 are both constitutive for postwar German literature in East and West.
The role of macrophages in the periodontal regeneration using Emdogain® gel
Authors: Fujishiro N. , Anan H. , Hamachi T. , Maeda K.
Published: August 2007

Background and Objective:  Emdogain® gel is clinically used as a periodontal regenerative material. However, the mechanism of the regeneration has not been completely elucidated. Although many studies have focused on the regenerative effect of Emdogain on connective tissue attachment and alveolar bone, the role of macrophages and the expression of growth factors remains unclear in the regeneration stimulated by Emdogain gel in vivo. The aim of this study was to investigate the effect of Emdogain gel on the expression of cytokines and growth factors by macrophages in vivo using a newly devised rat experimental periodontitis model.

Material and Methods:  Rat experimental periodontitis was induced by elevating a full‐thickness gingival flap and ligating silk threads around the first molars of the mandible. At 14 d after inducing experimental periodontitis, Emdogain gel or propylene glycol alginate was applied to the furcation area. The rats were killed 7 and 14 d after treatment with propylene glycol alginate or Emdogain gel. The expression of cytokines and growth factors, and the regeneration of periodontal tissue, were examined by histochemical and immunohistochemical methods.

Results:  Fourteen days after the induction of periodontitis, the resorption of alveolar bone at furcation was observed and cytokines such as interleukin‐1β, transforming growth factor‐β1, receptor activator of nuclear factor‐κB ligand, receptor activator of nuclear factor‐κB and osteoprotegerin were found. In the Emdogain‐treatment group, the formation of new acellular cementum and, more remarkably, recovery of the bone, were observed. The new bone formation ratio in the Emdogain treatment group was significantly higher than that of the propylene glycol alginate treatment group. Although the expression of cytokines such as interleukin‐1β, transforming growth factor‐β1, receptor activator of nuclear factor‐κB ligand and receptor activator of nuclear factor‐κB was very low, bone morphogenetic protein‐2‐ and bone morphogenetic protein‐4‐expressing macrophages were observed close to the root, and bone morphogenetic protein‐4‐expressing macrophages were mainly observed close to the bone surface at the furcation in the Emdogain‐treatment group.

Conclusion:  These results suggest that wound‐healing macrophages may express bone morphogenetic protein and play an important role in the regeneration of periodontal tissue at the furcation following the application of Emdogain gel.
The International Family Quality of Life Project: Goals and Description of a Survey Tool
Authors: Isaacs Barry J. , Brown Ivan , Brown Roy I. , Baum Nehama , Myerscough Ted , Neikrug Shimshon , Roth Dana , Shearer Jo , Wang Mian
Published: August 2007

Abstract  The International Family Quality of Life Project, begun in 1997, involves the collaboration of a team of researchers from Australia, Canada, Israel, and the United States whose aim was to conceptualize “family quality of life” and develop a survey tool. The authors describe the basis for the conceptualization and explain the survey development process. An initial version of the survey (the Family Quality of Life Survey—FQoLS‐2000) was used to collect FQoL data across several countries in the early 2000s. The experiences of survey respondents and administrators and subsequent data analysis suggested modifications that resulted in an updated version—the FQoLS‐2006. This new version focuses on 9 areas of family life: health, finances, family relationships, support from other people, support from disability‐related services, influence of values, careers and planning for careers, leisure and recreation, and community interaction. The authors explore each of these areas in relation to 6 underlying concepts: importance, opportunities, initiative, attainment, stability, and satisfaction. Other sections entail obtaining information on the family make‐up, family member, or members, with intellectual disability, and an overall summary of FQoL. The authors note that information from the FQoLS‐2006 should be useful for a wide variety of purposes related to providing supports to individuals and families.
Why Are People With Intellectual Disability Moved “Out‐of‐Area”?
Authors: Perry David W. , Shervington Tracy , Mungur Neil , Marston Geoff , Martin David , Brown Gill
Published: August 2007

Abstract  Some people with intellectual disabilities (ID) continue to be provided with accommodations that are outside their local area, away from familiar people and places. Although studies have been scarce on this topic, there is evidence to suggest that this does not always provide the best outcome for individuals in terms of quality of life. The authors undertook a survey to look at the personal characteristics of 89 persons with ID originally from the city of Coventry in the UK, and now situated by local health or social services authorities in locations other than the immediate Coventry area. The authors found that the number of people being placed “out‐of‐area” is increasing; among them are persons with autistic spectrum disorder (particularly those transitioning into adulthood), those with a past history of behavior resulting in action by the criminal justice system, and those with a history of aggression toward others. There are concerns that the commissioning and provision of “out‐of‐area” services echo the dehumanizing institutionalization policies that dominated the first part of the 20th century, are lacking in coordination, and are proving to be more expensive than locally provided services.
Regulated expression by PPARα and unique localization of 17β‐hydroxysteroid dehydrogenase type 11 protein in mouse intestine and liver
Authors: Yokoi Yasuhide , Horiguchi Yuka , Araki Makoto , Motojima Kiyoto
Published: August 2007

17β‐Hydroxysteroid dehydrogenase type 11 (17β‐HSD11) is a member of the short‐chain dehydrogenase/reductase family involved in the activation and inactivation of sex steroid hormones. We recently identified 17β‐HSD11 as a gene that is efficiently regulated by peroxisome proliferator‐activated receptor‐α PPARα in the intestine and the liver [Motojima K (2004) Eur J Biochem271, 4141–4146]. In this study, we characterized 17β‐HSD11 at the protein level to obtain information about its physiologic role in the intestine and liver. For this purpose, specific antibodies against 17β‐HSD11 were obtained. Western blotting analysis showed that administration of a peroxisome proliferator‐activated receptor‐α agonist induced 17β‐HSD11 protein in the jejunum but not in the colon, and to a much higher extent than in the liver of mice. A subcellular localization study using Chinese hamster ovary cells and green fluorescent protein‐tagged 17β‐HSD11 showed that it was mostly localized in the endoplasmic reticulum under normal conditions, whereas it was concentrated on lipid droplets when they were induced. A pulse‐chase experiment suggested that 17β‐HSD11 was redistributed to the lipid droplets via the endoplasmic reticulum. Immunohistochemical analysis using tissue sections showed that 17β‐HSD11 was induced mostly in intestinal epithelia and hepatocytes, with heterogeneous localization both in the cytoplasm and in vesicular structures. A subcellular fractionation study of liver homogenates confirmed that 17β‐HSD11 was localized mostly in the endoplasmic reticulum when mice were fed a normal diet, but was distributed in both the endoplasmic reticulum and the lipid droplets of which formation was induced by feeding a diet containing a proliferator‐activated receptor‐α agonist. Taken together, these data indicate that 17β‐HSD11 localizes both in the endoplasmic reticulum and in lipid droplets, depending on physiologic conditions, and that lipid droplet 17β‐HSD11 is not merely an endoplasmic reticulum contaminant or a nonphysiologically associated protein in the cultured cells, but a bona fide protein component of the membranes of both intracellular compartments.
Comprehensive interaction of dicalcin with annexins in frog olfactory and respiratory cilia
Authors: Uebi Tatsuya , Miwa Naofumi , Kawamura Satoru
Published: August 2007

Dicalcin (renamed from p26olf) is a dimer form of S100 proteins found in frog olfactory epithelium. S100 proteins form a group of EF‐hand Ca2+‐binding proteins, and are known to interact with many kinds of target protein to modify their activities. To determine the role of dicalcin in the olfactory epithelium, we identified its binding proteins. Several proteins in frog olfactory epithelium were found to bind to dicalcin in a Ca2+‐dependent manner. Among them, 38 kDa and 35 kDa proteins were most abundant. Our analysis showed that these were a mixture of annexin A1, annexin A2 and annexin A5. Immunohistochemical analysis showed that dicalcin and all of these three subtypes of annexin colocalize in the olfactory cilia. Dicalcin was found to be present in a quantity almost sufficient to bind all of these annexins. Colocalization of dicalcin and the three subtypes of annexin was also observed in the frog respiratory cilia. Dicalcin facilitated Ca2+‐dependent liposome aggregation caused by annexin A1 or annexin A2, and this facilitation was additive when both annexin A1 and annexin A2 were present. In this facilitation effect, the effective Ca2+ concentrations were different between annexin A1 and annexin A2, and therefore the dicalcin–annexin system in frog olfactory and respiratory cilia can cover a wide range of Ca2+ concentrations. These results suggested that this system is associated with abnormal increases in the Ca2+ concentration in the olfactory and other motile cilia.
Using directed evolution to improve the solubility of the C‐terminal domain of Escherichia coli aminopeptidase P
Authors: Liu Jian‐Wei , Hadler Kieran S. , Schenk Gerhard , Ollis David
Published: August 2007

There have been many approaches to solving problems associated with protein solubility. This article describes the application of directed evolution to improving the solubility of the C‐terminal metal‐binding domain of aminopeptidase P from Escherichia coli. During the course of experiments, the domain boundary and sequence were allowed to vary. It was found that extending the domain boundary resulted in aggregation with little improvement in solubility, whereas two changes to the sequence of the domain resulted in dramatic improvements in solubility. These latter changes occurred in the active site and abolished the ability of the protein to bind metals and hence catalyze its physiological reaction. The evidence presented here has led to the proposal that metals bind to the intact protein after it has folded and that the N‐terminal domain is necessary to stabilize the structure of the protein so that it is capable of binding metals. The acid residues responsible for binding metals tend to repel one another − in the absence of the N‐terminal domain, the C‐terminal domain does not fold properly and forms inclusion bodies. Evolution of the C‐terminal domain has removed the destabilizing effects of the metal ligands, but in so doing it has reduced the capacity of the domain to bind metals. In this case, directed evolution has identified active site residues that destabilize the domain structure.
Use of composts to manage corky root disease in organic tomato production
Authors: Hasna M.K. , Mårtensson A. , Persson P. , Rämert B.
Published: August 2007

Corky root disease of tomato caused by Pyrenochaeta lycopersici is an economically important disease in organic tomato production. This study aimed to evaluate the effects of various composts consisting of green manure, garden waste and horse manure against corky root disease through bioassay under greenhouse conditions, where soil naturally infested with P. lycopersici was used as a root substrate. The various composts were mixed at a rate of 20% (v/v) with the infested soil. Disease severity (measured as infected roots) in the unamended soil was compared with that in the soil–compost mixtures. One of the composts made from garden waste significantly reduced the disease, whereas horse manure compost significantly stimulated it. Lower concentrations of NH4‐N and total carbon and a higher concentration of Ca in the substrate were correlated with lower level of corky root disease. Addition of green manure or garden waste compost to the infested soil increased total microbial activity or population density of copiotrophic bacteria and actinomycetes, respectively. However, increased microbial activity or microbial population in soil–compost mixtures was not associated with a reduction in corky root disease severity in the present study.
Detecting Infiltration and Impacts of Introduced Water Using Strontium Isotopes
Authors: Brinck Elizabeth L. , Frost Carol D.
Published: August 2007

Water introduced to surface drainages, such as agricultural and roadway runoff, mine drainage, or coalbed natural gas (CBNG)–produced water, potentially can be of environmental concern. In order to mitigate potential environmental effects, it may be important to be able to trace water discharged to the surface as it infiltrates and interacts with near‐surface aquifers. We have chosen to study water withdrawn during CBNG production for isotope tracing in the hyporheic zone because it poses a variety of economic, environmental, and policy issues in the Rocky Mountain states. Ground water quality must be protected as CBNG water is added to semiarid ecosystems. Strontium (Sr) isotopes are effective fingerprints of the aquifer from which water originates. In this study, CBNG water was found to have a higher 87Sr/86Sr ratio than the local alluvial aquifer water. This measurable difference allows the strontium isotope ratio and concentration to be used as tracers of CBNG water following its discharge to the surface. The dissolution and mobilization of salts from soil are an important contributor to ground water quality degradation. In the Powder River basin of Wyoming, the soils are calcium carbonate–buffered systems. The chemical similarity of strontium to calcium allows it to substitute into calcium minerals and enabled us to use strontium isotopes to identify calcium salts mobilized from the soil. Strontium isotopes are an effective monitor of the source of ions and the volume and direction of introduced water flow in the hyporheic zone.
Bipiperidinyl Carboxylic Acid Amides as Potent, Selective, and Functionally Active CCR4 Antagonists
Authors: Kuhn Cyrille F. , Bazin Marc , Philippe Laurence , Zhang Jiansu , Tylaska Laurie , Miret Juan , Bauer Paul H.
Published: August 2007

A cell‐based assay for the chemokine G‐protein‐coupled receptor CCR4 was developed, and used to screen a small‐molecule compound collection in a multiplex format. A series of bipiperidinyl carboxylic acid amides amenable to parallel chemistry were derived that were potent and selective antagonists of CCR4. One prototype compound was shown to be active in a functional model of chemotaxis, making it a useful chemical tool to explore the role of CCR4 in asthma, allergy, diabetes, and cancer.
Structure–activity Relationships of Amyloid Beta‐aggregation Inhibitors Based on Curcumin: Influence of Linker Length and Flexibility
Authors: Reinke Ashley A. , Gestwicki Jason E.
Published: August 2007

Self‐assembly of amyloid beta into fibrillar plaques is characteristic of Alzheimer’s disease and oligomers of this peptide are believed to be involved in neurodegeneration. Natural organic dyes, such as congo red and curcumin, bind tightly to amyloid beta and, at higher concentrations, block its self‐assembly. The ability of these molecules to prevent amyloid accumulation has generated interest in understanding which of their structural features contribute to inhibitory potency. In general, amyloid beta ligands tend to be flat, planar molecules with substituted aromatic end groups; however, a comprehensive structure–activity study has not been reported. To better understand these ligands, we surveyed the effect of three prominent features on inhibition of amyloid aggregation: the presence of two aromatic end groups, the substitution pattern of these aromatics, and the length and flexibility of the linker region. We found that modification of any one of the modules has profound effects on activity. Further, we report that the optimal length of the linker lies within a surprisingly narrow regime (6–19 Å). These results offer insight into the key chemical features required for inhibiting amyloid beta aggregation. In turn, these findings help define the nature of the docking site for small molecules on the amyloid beta surface.
N‐terminal bis‐(2‐Chloroethyl)amino and Fluorosulphonyl Analogues of Calcitonin Gene‐Related Peptide(8‐37): Irreversible Antagonists at Calcitonin Gene‐Related Peptide Receptors
Authors: Taylor Christopher K. , Abel Peter W. , Hulce Martin , Smith D. David
Published: August 2007

Synthesis of the first irreversible calcitonin gene‐related peptide receptor antagonists is described. bis‐(2‐Chloroethyl)amino and fluorosulphonyl groups were incorporated into the 4‐position of the N‐terminal benzoyl group of a potent competitive antagonist, N‐α‐benzoyl‐h‐α‐CGRP(8‐37) (analogues 4 and 6). Based on previous structure–activity relationships, a second pair of N‐terminally modified analogues was synthesized containing a novel benzylated‐His residue in position 10 (analogues 5 and 7). In separate experiments, SK‐N‐MC cells and mouse thoracic aortas were bathed in solutions containing 5 μm and 1.5 μm of each analogue, respectively. After extensive washing, calcitonin gene‐related peptide concentration–response curves were generated for cAMP production in SK‐N‐MC cells and relaxation of mouse aortas. All analogues caused >20% reductions in maximal calcitonin gene‐related peptide efficacy in both assays with analogue 5 containing an N‐terminal bis‐(2‐chloroethyl)amino‐benzoyl group and a benzylated‐His10 residue completely abolishing cAMP production in SK‐N‐MC cells. Reductions in maximal responses were dependent on the analogue concentration. Analogue 4 also caused more than 10‐fold reductions in the potency of the calcitonin gene‐related peptide‐mediated effects, whereas analogues 5, 6 and 7 have no significant effect on calcitonin gene‐related peptide potency. These data indicate that all analogues bind irreversibly to calcitonin gene‐related peptide receptors. The bis‐(2‐chloroethyl)amino‐modified analogues 4 and 5 were more effective than the fluorosulphonyl‐modified analogues 6 and 7.
A Novel Contour Generation Algorithm for Surface Reconstruction From Dexel Data
Authors: Zhang Weihan , Peng Xiaobo , Leu Ming C. , Zhang Wei
Published: August 2007

This paper presents a method of reconstructing a triangular surface patch from dexel data generated by ray casting to represent solid models for applications, such as virtual sculpting and numerically controlled (NC) machining simulation. A novel contour generation algorithm is developed to convert dexel data into a series of planar contours on parallel slices. The algorithm categorizes the dexels on two adjacent rays into different groups by using a “grouping” criterion. The dexel points in the same group are connected using a set of rules to form subboundaries. After checking the connections among all the dexel points on one slice, a connection table is created and used to obtain the points of connection in a counterclockwise sequence for every contour. Finally, the contours on all the parallel slices are tiled to obtain triangular facets of the boundary surface of the 3D object. Computational costs and memory requirements are analyzed, and the computational complexity analysis is verified by numerical experiments. Example applications are given to demonstrate the described method.
Global Bifurcation Analysis of a Nonlinear Road Vehicle System
Authors: Liu Zhaoheng , Payre Guy
Published: August 2007

This paper investigates the global stability behavior present near a bifurcation point of a nonlinear road vehicle system. The nonlinear behavior of the system is determined by reducing its dimensions according to the center manifold theory applied to a nongeneric case. A generalized Hopf bifurcation is analyzed by unfolding the limit cycle mean amplitude equation into a two-parameter space. The numerical application of the analytical framework demonstrates the coexistence of two limit cycles for certain ranges of physical and driver parameter values.
The Hamel Representation: A Diagonalized Poincaré Form
Authors: Sovinsky Michael C. , Hurtado John E. , Griffith D. Todd , Turner James D.
Published: August 2007

The Poincaré equations, also known as Lagrange’s equations in quasicoordinates, are revisited with special attention focused on a diagonal form. The diagonal form stems from a special choice of generalized speeds that were first introduced by Hamel (Hamel, G., 1967, Theorctische Mechanik, Springer-Verlag, Berlin, Secs. 235 and 236) nearly a century ago. The form has been largely ignored because the generalized speeds create so-called Hamel coefficients that appear in the governing equations and are based on the partial derivative of a mass-matrix factorization. Consequently, closed-form expressions for the Hamel coefficients can be difficult to obtain. In this paper, a newly developed operator overloading technique is used within a simulation code to automatically generate the Hamel coefficients through an exact partial differentiation together with a numerical evaluation. This allows the diagonal form of Poincaré’s equations to be numerically integrated for system simulation. The diagonal form and the techniques used to generate the Hamel coefficients are applicable to general systems, including systems with closed kinematic chains. Because of Hamel’s original influence, these special Poincaré equations are called the Hamel representations and their usefulness in dynamic simulation and control is investigated.
Nonlinear Hybrid-Mode Resonant Forced Oscillations of Sagged Inclined Cables at Avoidances
Authors: Rega Giuseppe , Srinil Narakorn
Published: August 2007

We investigate nonlinear forced oscillations of sagged inclined cables under planar 1:1 internal resonance at avoidance. To account for frequency avoidance phenomena and associated hybrid modes, actually distinguishing inclined cables from horizontal cables, asymmetric inclined static configurations are considered. Emphasis is placed on highlighting nearly tuned 1:1 resonant interactions involving coupled hybrid modes. The inclined cable is subjected to a uniformly distributed vertical harmonic excitation at primary resonance of a high-frequency mode. Approximate nonlinear partial-differential equations of motion, capturing overall displacement coupling and dynamic extensibility effect, are analytically solved based on a multimode discretization and a second-order multiple scale approach. Bifurcation analyses of both equilibrium and dynamic solutions are carried out via a continuation technique, highlighting the influence of system parameters on internally resonant forced dynamics of avoidance cables. Direct numerical integrations of modulation equations are also performed to validate the continuation prediction and characterize nonlinear coupled dynamics in post-bifurcation states. Depending on the elasto-geometric (cable sag and inclination) and control parameters, and on assigned initial conditions, the hybrid modal interactions undergo several kinds of bifurcations and nonlinear phenomena, along with meaningful transition from periodic to quasiperiodic and chaotic responses. Moreover, corresponding spatio-temporal distributions of cable nonlinear dynamic displacement and tension are manifested.
Comparison of the Classical Formulation With the Reference Conditions Formulation for Dynamic Flexible Multibody Systems
Authors: Drab C. B. , Haslinger J. R. , Pfau R. U. , Offner G.
Published: August 2007

Within the framework of the “floating frame of reference” formulation for dynamic flexible multibody systems, the separation of local and global motion is important. We compare the new approach with reference conditions as algebraic constraints with the classical one leading to a system of ordinary differential equations. The approach using reference conditions is motivated either from the need of keeping the error introduced when linearizing the elastic forces as small as possible (Buckens frame) or from minimizing the relative kinetic energy contained in the elastic deformations (Tisserand frame). The reference conditions impose algebraic constraints on the body level leading to a differential-algebraic equation (DAE) to be solved. The equivalence and the differences of the two approaches are shown. The index of the DAE system with reference conditions is shown to be either 2 or 1.
Dynamic Analysis and Counterweight Optimization of the 2-DOF Parallel Manipulator of a Hybrid Machine Tool
Authors: Wu Jun , Wang Jinsong , Wang Liping , Li Tiemin , Liu Yue
Published: August 2007

This paper focuses on the dynamic modeling and counterweight optimization of the two degree of freedom planar parallel manipulator, which is a subpart of a hybrid machine tool. Based on a kinematic analysis, the dynamic equation is derived by using the Newton-Euler approach. Then, three counterweight modes are presented for the parallel manipulator. According to the cutting force model and motion planning of the cutting tool, the dynamic simulations with three counterweight modes are performed, and the mass of counterweight in each counterweight mode is optimized by minimizing the sum of mean square values of actuator forces. The simulations show that the optimal mass of counterweights does not equal the total mass of moving parts of the parallel manipulator, and each counterweight mode has its advantage and disadvantage. Considering the ease in which a counterweight can be implemented, the counterweight mode where two counterweights are connected to two sliders is adopted for the parallel manipulator.
Integration of Large Deformation Finite Element and Multibody System Algorithms
Authors: Shabana Ahmed A. , Bauchau Olivier A. , Hulbert Gregory M.
Published: August 2007

This paper presents an overview of research and development efforts that are currently being devoted to integrate large deformation finite element formulations with flexible multibody system algorithms. The goal is to develop computer simulation capabilities for the analysis of physics and engineering models with significant details. The successful development of such new and integrated algorithms will also allow modeling and simulation of systems that cannot be solved using existing computer algorithms and codes. One of the main difficulties encountered in this integration process is attributed to the fact that the solution procedures used in finite element codes differ significantly from those used in general-purpose flexible multibody system codes. Finite element methods employ the corotational formulations that are often used with incremental solution procedures. Flexible multibody computer codes, on the other hand, do not, in general, use incremental solution procedures. Three approaches are currently being explored by academic institutions and the software industry. In the first approach, gluing algorithms that aim at performing successful simulations by establishing an interface between existing codes are used. Using different coordinates and synchronizing the time stepping are among several challenging problems that are encountered when gluing algorithms are used. In the second approach, multibody system capabilities are implemented in existing finite element algorithms that are based on large rotation vector formulations. For the most part, corotational formulations and incremental solution procedures are used in this case. In the third approach, a new large deformation finite element formulation that can be successfully implemented in flexible multibody system computer algorithms that employ nonincremental solution procedures is introduced. The approach that is now being developed in several institutions is based on the finite element absolute nodal coordinate formulation. Such a formulation can be systematically implemented in general-purpose flexible multibody system computer algorithms. Nonlinear constraint equations that describe mechanical joints between different bodies can be formulated in terms of the absolute coordinates in a straightforward manner. The coupling between the motion of rigid, flexible, and very flexible bodies can also be accurately described. The successful integration of large deformation finite element and multibody system algorithms will lead to a new generation of computer codes that can be systematical and efficiently used in the analysis of many engineering applications.