bluuebunny/crossref_metadata_2025 huggingface dataset:
Why Is Golden Rice Golden (Yellow) Instead of Red?
Authors: Schaub Patrick , Al-Babili Salim , Drake Rachel , Beyer Peter
Published: April 2005

The endosperm of Golden Rice (Oryza sativa) is yellow due to the accumulation of β-carotene (provitamin A) and xanthophylls. The product of the two carotenoid biosynthesis transgenes used in Golden Rice, phytoene synthase (PSY) and the bacterial carotene desaturase (CRTI), is lycopene, which has a red color. The absence of lycopene in Golden Rice shows that the pathway proceeds beyond the transgenic end point and thus that the endogenous pathway must also be acting. By using TaqMan real-time PCR, we show in wild-type rice endosperm the mRNA expression of the relevant carotenoid biosynthetic enzymes encoding phytoene desaturase, ζ-carotene desaturase, carotene cis-trans-isomerase, β-lycopene cyclase, and β-carotene hydroxylase; only PSY mRNA was virtually absent. We show that the transgenic phenotype is not due to up-regulation of expression of the endogenous rice pathway in response to the transgenes, as was suggested to be the case in tomato (Lycopersicon esculentum) fruit, where CRTI expression resulted in a similar carotenoid phenomenon. This means that β-carotene and xanthophyll formation in Golden Rice relies on the activity of constitutively expressed intrinsic rice genes (carotene cis-trans-isomerase, α/β-lycopene cyclase, β-carotene hydroxylase). PSY needs to be supplemented and the need for the CrtI transgene in Golden Rice is presumably due to insufficient activity of the phytoene desaturase and/or ζ-carotene desaturase enzyme in endosperm. The effect of CRTI expression was also investigated in leaves of transgenic rice and Arabidopsis (Arabidopsis thaliana). Here, again, the mRNA levels of intrinsic carotenogenic enzymes remained unaffected; nevertheless, the carotenoid pattern changed, showing a decrease in lutein, while the β-carotene-derived xanthophylls increased. This shift correlated with CRTI-expression and is most likely governed at the enzyme level by lycopene-cis-trans-isomerism. Possible implications are discussed.
Antioxidant mechanism of heme oxygenase-1 involves an increase in superoxide dismutase and catalase in experimental diabetes
Authors: Turkseven Saadet , Kruger Adam , Mingone Christopher J. , Kaminski Pawel , Inaba Muneo , Rodella Luigi F. , Ikehara Susumu , Wolin Michael S. , Abraham Nader G.
Published: April 2005

Increased heme oxygenase (HO)-1 activity attenuates endothelial cell apoptosis and decreases superoxide anion (O2−) formation in experimental diabetes by unknown mechanisms. We examined the effect of HO-1 protein and HO activity on extracellular SOD (EC-SOD), catalase, O2−, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) levels and vascular responses to ACh in control and diabetic rats. Vascular EC-SOD and plasma catalase activities were significantly reduced in diabetic compared with nondiabetic rats ( P < 0.05). Upregulation of HO-1 expression by intermittent administration of cobalt protoporphyrin, an inducer of HO-1 protein and activity, resulted in a robust increase in EC-SOD but no significant change in Cu-Zn-SOD. Administration of tin mesoporphyrin, an inhibitor of HO-1 activity, decreased EC-SOD protein. Increased HO-1 activity in diabetic rats was associated with a decrease in iNOS but increases in eNOS and plasma catalase activity. On the other hand, aortic ring segments from diabetic rats exhibited a significant reduction in vascular relaxation to ACh, which was reversed with cobalt protoporphyrin treatment. These data demonstrate that an increase in HO-1 protein and activity, i.e., CO and bilirubin production, in diabetic rats brings about a robust increase in EC-SOD, catalase, and eNOS with a concomitant increase in endothelial relaxation and a decrease in O2−. These observations in experimental diabetes suggest that the vascular cytoprotective mechanism of HO-1 against oxidative stress requires an increase in EC-SOD and catalase.
Regulation of cardiac malonyl-CoA content and fatty acid oxidation during increased cardiac power
Authors: King Kristen L. , Okere Isidore C. , Sharma Naveen , Dyck Jason R. B. , Reszko Aneta E. , McElfresh Tracy A. , Kerner Janos , Chandler Margaret P. , Lopaschuk Gary D. , Stanley William C.
Published: April 2005

Myocardial fatty acid oxidation is regulated by carnitine palmitoyltransferase I (CPT I), which is inhibited by malonyl-CoA. Increased cardiac power causes a fall in malonyl-CoA content and accelerated fatty acid oxidation; however, the mechanism for the decrease in malonyl-CoA is unclear. Malonyl-CoA is formed by acetyl-CoA carboxylase (ACC) and degraded by malonyl-CoA decarboxylase (MCD); thus a fall in malonyl-CoA could be due to activation of MCD, inhibition of ACC, or both. This study assessed the effects of increased cardiac power on malonyl-CoA content and ACC and MCD activities. Anesthetized pigs were studied under control conditions and during increased cardiac power in response to dobutamine infusion and aortic constriction alone, under hyperglycemic conditions, or with the CPT I inhibitor oxfenicine. An increase in cardiac power was accompanied by increased myocardial O2consumption, decreased malonyl-CoA concentration, and increased fatty acid oxidation. There were no differences among groups in activity of ACC or AMP-activated protein kinase (AMPK), which physiologically inhibits ACC. There also were no differences in Vmaxor Kmof MCD. Previous studies have demonstrated that AMPK can be inhibited by protein kinase B (PKB); however, PKB was activated by dobutamine and the elevated insulin that accompanied hyperglycemia, but there was no effect on AMPK activity. In conclusion, the fall in malonyl-CoA and increase in fatty acid oxidization that occur with increased cardiac work were not due to inhibition of ACC or activation of MCD, suggesting alternative regulatory mechanisms for the work-induced decrease in malonyl-CoA concentration.
Changes in PKB/Akt and calcineurin signaling during recovery in atrophied soleus muscle induced by unloading
Authors: Sugiura Takao , Abe Noritaka , Nagano Mai , Goto Katsumasa , Sakuma Kunihiro , Naito Hisashi , Yoshioka Toshitada , Powers Scott K.
Published: April 2005

Protein kinase B [PKB, also known as Akt (PKB/Akt)] and calcineurin (CaN) are postulated to play important roles in integrating intracellular signaling in skeletal muscle in response to disuse and increased muscle loading. These experiments investigated changes in signal transduction of the downstream pathways of PKB/Akt and CaN during recovery following disuse-induced muscle atrophy. A 10-day period of hindlimb unloading (HLU) via tail suspension (male rats) was used to produce soleus muscle atrophy. Muscle recovery was achieved by returning animals to normal ambulation for 3–10 days. HLU resulted in significant muscle atrophy and a slow-to-fast fiber transition as revealed by appearance of type IId/x and IIb myosin heavy chain (MHC) isoforms. Muscle mass in HLU animals recovered to control (Con) levels after 10 days of reloading, but the fast-to-slow shift in muscle MHC was incomplete, as indicated by the continued presence of type IId/x MHC. Ten days of HLU resulted in a significant decrease (−43%) in muscle levels of phosphorylated PKB/Akt. In contrast, muscle levels of phosphorylated PKB/Akt were greater (+56%) in HLU than in Con animals early after the onset of reloading (3 days). Soleus levels of phosphorylated p70S6K were significantly higher (+26%) in HLU animals after 3 days of muscle reloading. Muscle levels of phosphorylated PKB/Akt and phosphorylated p70S6K returned to Con levels by day 10 of recovery. Moreover, muscle CaN levels were significantly higher than Con levels after 10 days of muscle reloading. These findings are consistent with the hypothesis that PKB/Akt and its downstream mediators are active in the regrowth of muscle mass during the early periods of recovery from muscle atrophy. Our data support the concept that CaN is involved in muscle remodeling during the later phases of recovery from disuse muscle atrophy.
Short photoperiod exposure increases adipocyte sensitivity to noradrenergic stimulation in Siberian hamsters
Authors: Bowers Robert R. , Gettys Thomas W. , Prpic Veronica , Harris Ruth B. S. , Bartness Timothy J.
Published: April 2005

Siberian hamsters ( Phodopus sungorus) exhibit a naturally occurring, reversible seasonal obesity with body fat peaking in long “summerlike” days (LDs) and reaching a nadir in short “winterlike” days (SDs). These SD-induced decreases in adiposity are mediated largely via sympathetic nervous system (SNS) innervation of white adipose tissue (WAT), as indicated by increased WAT norepinephrine (NE) turnover. We examined whether SDs also increase sensitivity to NE-stimulated lipolysis. This was accomplished by measuring NE- and β3-adrenoceptor (β3-AR) agonist (BRL-37344)-induced lipolysis (glycerol release) as well as NE-induced cAMP accumulation by inguinal, epididymal, and retroperitoneal WAT (IWAT, EWAT, and RWAT) in isolated adipocytes of LD- and SD-housed hamsters. SDs increased potency/efficacy of NE-triggered lipolysis in a temporally and fat pad-specific manner. Thus when WAT pad mass decreased most rapidly (5 wk of SDs), potency (sensitivity/EC50) and efficacy (maximal response asymptote) of NE-stimulated lipolysis were increased for all WAT pads and also at 10 wk for IWAT compared with their LD counterparts. SD enhancement of lipolysis was similar for NE and BRL-37344 in IWAT adipocytes. These results, coupled with our previous demonstration that SDs upregulate WAT β3-AR mRNA expression, suggest that increased β3-ARs mediated the SD-induced increased NE sensitivity. NE-stimulated adipocyte accumulation of cAMP was greater after 5 wk of SDs for IWAT and EWAT and after 10 wk of SDs for IWAT compared with LDs, with no photoperiod effect for RWAT. Therefore, the SD-induced increase in SNS drive to WAT and increased sensitivity to this drive may work together to increase lipolysis in SDs.
“Facilis descensus averni est”: The Allied Bombing of Germany and the Issue of German Suffering
Authors: Childers Thomas
Published: April 2005

Contemplatingwith dread the slide toward war between Japan and the United States in the autumn of 1941, Joseph Grew, the American ambassador to Tokyo, noted gloomily in his diary: “Facilis descensus averni est”—the descent into Hell is easy. Events in Europe and China had already given eloquent testimony to that grim axiom, confirming all too clearly that among the first casualties of war are peacetime notions of morality. Grew's foreboding was more than justified. Before the Second World War would come to a close in the summer of 1945, it had become the most destructive conflict in human history, with fifty-five million dead, millions more broken, either physically or psychologically, thirty million refugees, and still millions more who had simply vanished. Continents had been ravaged, great cities laid waste, and a tidal wave of destruction left behind a landscape of unparalleled human suffering. A war that began with the major powers pledging to refrain from “the bombardment from the air of civilian populations or unfortified cities”—Hitler piously committed Germany to conduct the war “in a chivalrous and humane manner”—ended with a mushroom cloud over Nagasaki.
Air Wars, Memory Wars
Authors: Nolan Mary
Published: April 2005

TheGerman preoccupation with the Nazi past, with issues of guilt, responsibility, and victimization “… doesn't end. Never will it end,” to quote the resigned note on which Günter Grass concluded his latest novel,Crabwalk. It manifests itself in ever new forms, as different parts of the past, which may or may not have been repressed, come to the fore and are painfully reconstructed, tentatively probed, and reluctantly and often only partially accepted. Each new perspective on the past reorders, sometimes even shatters, the previous mosaic. Recall the impact of the filmHolocaustor of the Wehrmacht exhibition. A similar phenomenon is now occurring—or so some hope and others fear. Since 2002 German suffering, rather than German guilt, has become the principal theme in discourses about the past. The firebombing of Hamburg and Dresden, the sinking of theWilhelm Gustloff, “moral bombing,” mass rape, and ethnic cleansing dominate historical and literary production and public debate as the Eastern Front, war crimes, and the pervasive knowledge of the Holocaust did in the mid- and late-1990s, and the uniqueness of the Holocaust and its central place within the Third Reich did a decade before that.
Rhetoric and Tertullian's De Virginibus Velandis
Authors: Dunn Geoffrey
Published: April 2005

Tertullian's de Virginibus Velandis is not simply a somewhat neglected ascetic treatise but a rhetorical treatise about asceticism. The use of classical rhetoric as a modern interpretative tool for early Christian literature is common, although, as witnessed in an article recentlyin this journal, not without its critics. In this deliberative treatise Tertullian argued from Scripture (3.5c-6.3), natural law (7.1-8.4) and Christian discipline (9.1-15.3) that from puberty Christian female virgins ought to be veiled when in public. The custom of some Carthaginian virginsnot being veiled when the church gathered was attacked as being contrary to the truth. What we find is Tertullian's overwhelming concern for fidelity to the regula fidei. The presence of a well-developed rhetorical structure in de Virginibus Velandis is an argument for datingit after de Oratione, where Tertullian made some similar points, though in a less cohesive and more rudimentary manner.
Nitor Omnibus Unus? Beobachtungen Zur Farbgestaltung Im ,martinellus'
Authors:   Vielberg
Published: April 2005

Colour words are used frequently by pagan novelists as well as epic and lyric poets of the first and second century A.D. Yet they are almost avoided in biblical and early Christian literature. So we ask how colour words were used by later Christian authors usurping pagan literature more freely. In order to find an answer we concentrate on the so-called ,,Martinellus", a corpus of hagiographical texts, mainly on the life of St Martin, written in prose and verse by Sulpicius Severus, Paulinus Petricordensis and Venantius Fortunatus. In spite of the close intertextual relationship between their works some differences become apparent. Severus is still using colour words sparingly, whilst his successors get more and more accustomed to their use; especially for the symbolic display of wealth, power and social prestige and where the praetexts are missing like in the prologues and epilogues of the hagiographical epics.
Windows .NET Network Distributed Basic Local Alignment Search Toolkit (W.ND-BLAST)
Authors: Dowd Scot E , Zaragoza Joaquin , Rodriguez Javier R , Oliver Melvin J , Payton Paxton R
Published: April 2005

Background

BLAST is one of the most common and useful tools for Genetic Research. This paper describes a software application we have termed Windows .NET Distributed Basic Local Alignment Search Toolkit (W.ND-BLAST), which enhances the BLAST utility by improving usability, fault recovery, and scalability in a Windows desktop environment. Our goal was to develop an easy to use, fault tolerant, high-throughput BLAST solution that incorporates a comprehensive BLAST result viewer with curation and annotation functionality.

Results

W.ND-BLAST is a comprehensive Windows-based software toolkit that targets researchers, including those with minimal computer skills, and provides the ability increase the performance of BLAST by distributing BLAST queries to any number of Windows based machines across local area networks (LAN). W.ND-BLAST provides intuitive Graphic User Interfaces (GUI) for BLAST database creation, BLAST execution, BLAST output evaluation and BLAST result exportation. This software also provides several layers of fault tolerance and fault recovery to prevent loss of data if nodes or master machines fail. This paper lays out the functionality of W.ND-BLAST. W.ND-BLAST displays close to 100% performance efficiency when distributing tasks to 12 remote computers of the same performance class. A high throughput BLAST job which took 662.68 minutes (11 hours) on one average machine was completed in 44.97 minutes when distributed to 17 nodes, which included lower performance class machines. Finally, there is a comprehensive high-throughput BLAST Output Viewer (BOV) and Annotation Engine components, which provides comprehensive exportation of BLAST hits to text files, annotated fasta files, tables, or association files.

Conclusion

W.ND-BLAST provides an interactive tool that allows scientists to easily utilizing their available computing resources for high throughput and comprehensive sequence analyses. The install package for W.ND-BLAST is freely downloadable from http://liru.ars.usda.gov/mainbioinformatics.html. With registration the software is free, installation, networking, and usage instructions are provided as well as a support forum.
Bifrontal transcranial direct current stimulation slows reaction time in a working memory task
Authors: Marshall Lisa , Mölle Matthias , Siebner Hartwig R , Born Jan
Published: April 2005

Background

Weak transcortical direct current stimulation (tDCS) applied to the cortex can shift the membrane potential of superficial neurons thereby modulating cortical excitability and activity. Here we test the possibility of modifying ongoing activity associated with working memory by tDCS. The concept of working memory applies to a system that is capable of transiently storing and manipulating information, as an integral part of the human memory system. We applied anodal and cathodal transcranial direct current (tDCS) stimulation (260 μA) bilaterally at fronto-cortical electrode sites on the scalp over 15 min repeatedly (15 sec-on/15 sec-off) as well as sham-tDCS while subjects performed a modified Sternberg task.

Results

Reaction time linearly increased with increasing set size. The slope of this increase was closely comparable for real and sham stimulation indicating that our real stimulation did not effect time required for memory scanning. However, reaction time was slowed during both anodal and cathodal stimulation as compared to placebo (p < 0.05) indicating that real stimulation hampered neuronal processing related to response selection and preparation.

Conclusion

Intermittent tDCS over lateral prefrontal cortex during a working memory task impairs central nervous processing related to response selection and preparation. We conclude that this decrease in performance by our protocol of intermittent stimulation results from an interference mainly with the temporal dynamics of cortical processing as indexed by event-related sustained and oscillatory EEG activity such as theta.
Hsp27 and axonal growth in adult sensory neurons in vitro
Authors: Williams Kristy L , Rahimtula Masuma , Mearow Karen M
Published: April 2005

Background

Neurite growth can be elicited by growth factors and interactions with extracellular matrix molecules like laminin. Among the targets of the signalling pathways activated by these stimuli are cytoskeletal elements, such as actin, tubulin and neurofilaments. The cytoskeleton can also be modulated by other proteins, such as the small heat shock protein Hsp27. Hsp27 interacts with actin and tubulin in non-neuronal cells and while it has been suggested to play a role in the response of some neurons to injury, there have been no direct studies of its contribution to axonal regeneration.

Results

We have investigated neurite initiation and process extension using cultures of adult dorsal root ganglion (DRG) sensory neurons and a laminin stimulation paradigm. Employing confocal microscopy and biochemical analyses we have examined localization of Hsp27 at early and later stages of neurite growth. Our results show that Hsp27 is colocalized with actin and tubulin in lamellopodia, filopodia, focal contacts and mature neurites and growth cones. Disruption of the actin cytoskeleton with cytochalasin D results in aberrant neurite initiation and extension, effects which may be attributable to alterations in actin polymerization states. Inhibition of Hsp27 phosphorylation in our cultures results in an atypical growth pattern that may be attributable to an effect of pHsp27 on the stability of the actin cytoskeleton.

Conclusion

We observed colocalization of the phosphorylated and non-phosphorylated forms of Hsp27 with actin and tubulin in both very early and later stages of neurite growth from cultured adult DRG neurons. The colocalization of Hsp27 and pHsp27 with actin in lamellopodia and focal contacts at early stages of neurite growth, and in processes, branch points and growth cones at later stages, suggests that Hsp27 may play a role in neuritogenesis and subsequent neurite extension, and potentially in the patterning of this growth. Hsp27 has been reported to play a key role in modulating actin cytoskeletal dynamics as an actin-capping protein in non-neuronal cells. Our results suggest that this may also be the case in neurons and support a role for Hsp27 in neurite outgrowth via its phosphorylation state-dependent interactions with actin.
Absence of association between angiotensin converting enzyme polymorphism and development of adult respiratory distress syndrome in patients with severe acute respiratory syndrome: a case control study
Authors: Chan KC Allen , Tang Nelson LS , Hui David SC , Chung Grace TY , Wu Alan KL , Chim Stephen SC , Chiu Rossa WK , Lee Nelson , Choi KW , Sung YM , Chan Paul KS , Tong YK , Lai ST , Yu WC , Tsang Owen , Lo YM Dennis
Published: April 2005

Background

It has been postulated that genetic predisposition may influence the susceptibility to SARS-coronavirus infection and disease outcomes. A recent study has suggested that the deletion allele (D allele) of the angiotensin converting enzyme (ACE) gene is associated with hypoxemia in SARS patients. Moreover, the ACE D allele has been shown to be more prevalent in patients suffering from adult respiratory distress syndrome (ARDS) in a previous study. Thus, we have investigated the association between ACE insertion/deletion (I/D) polymorphism and the progression to ARDS or requirement of intensive care in SARS patients.

Method

One hundred and forty genetically unrelated Chinese SARS patients and 326 healthy volunteers were recruited. The ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis.

Results

There is no significant difference in the genotypic distributions and the allelic frequencies of the ACE I/D polymorphism between the SARS patients and the healthy control subjects. Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients. In multivariate logistic analysis, age is the only factor associated with the development of ARDS while age and male sex are independent factors associated with the requirement of intensive care.

Conclusion

The ACE I/D polymorphism is not directly related to increased susceptibility to SARS-coronavirus infection and is not associated with poor outcomes after SARS-coronavirus infection.
Does socioeconomic status affect mortality subsequent to hospital admission for community acquired pneumonia among older persons?
Authors: Vrbova Linda , Mamdani Muhammad , Moineddin Rahim , Jaakimainen Liisa , Upshur Ross EG
Published: April 2005

Background

Low socioeconomic status has been associated with increased morbidity and mortality for various health conditions. The purpose of this study was twofold: to examine the mortality experience of older persons admitted to hospital with community acquired pneumonia and to test the hypothesis of whether an association exists between socioeconomic status and mortality subsequent to hospital admission for community-acquired pneumonia.

Methods

A population based retrospective cohort study was conducted including all older persons patients admitted to Ontario hospitals with community acquired pneumonia between April 1995 and March 2001. The main outcome measures were 30 day and 1 year mortality subsequent to hospital admission for community-acquired pneumonia.

Results

Socioeconomic status for each patient was imputed from median neighbourhood income. Multivariate analyses were undertaken to adjust for age, sex, co-morbid illness, hospital and physician characteristics. The study sample consisted of 60,457 people. Increasing age, male gender and high co-morbidity increased the risk for mortality at 30 days and one year. Female gender and having a family physician as attending physician reduced mortality risk.

The adjusted odds of death after 30-days for the quintiles compared to the lowest income quintile (quintile 1) were 1.02 (95% CI: 0.95–1.09) for quintile 2, 1.04 (95% CI: 0.97–1.12) for quintile 3, 1.01 (95% CI: 0.94–1.08) for quintile 4 and 1.03 (95% CI: 0.96–1.12) for the highest income quintile (quintile 5). For 1 year mortality, compared to the lowest income quintile the adjusted odds ratios were 1.01 (95% CI: 0.96–1.06) for quintile 2, 0.99 (95% CI: 0.94–1.04) for quintile 3, 0.99 (95% CI: 0.93–1.05) for quintile 4 and 1.03 (95% CI: 0.97–1.10) for the highest income quintile.

Conclusion

Socioeconomic status is not associated with mortality in the older persons from community-acquired pneumonia in Ontario, Canada.
Clinical utility of serum HER2/neu in monitoring and prediction of progression-free survival in metastatic breast cancer patients treated with trastuzumab-based therapies
Authors: Esteva Francisco J , Cheli Carol D , Fritsche Herbert , Fornier Monica , Slamon Dennis , Thiel Robert P , Luftner Diana , Ghani Farooq
Published: April 2005

Introduction

The purpose of this retrospective study was to determine the clinical utility of serum HER2/neu in monitoring metastatic breast cancer patients undergoing trastuzumab-based therapy and to compare these results with those obtained using cancer antigen (CA) 15-3. We also sought to determine whether early changes in serum HER2/neu concentrations could be a predictor of progression-free survival.

Methods

Sera were obtained retrospectively from 103 women at four medical institutions. Patients eligible for participation were women with metastatic breast cancer who had HER2/neu tissue overexpression and were scheduled to be treated with trastuzumab with or without additional therapies as per the established practices of the treating physicians. A baseline serum sample for each patient was taken before trastuzumab-based therapy was started. Patients were subsequently monitored over 12 to 20 months and serum samples were taken at the time of clinical assessment and tested with Bayer's HER2/neu and CA15-3 assays.

Results

Concordance between clinical status in patients undergoing trastuzumab-based treatment and HER2/neu and CA15-3 used as single tests was 0.793 and 0.627, respectively, and increased to 0.829 when the tests were used in combination. Progression-free survival times did not differ significantly in patients with elevated baseline HER2/neu concentrations (≥ 15 ng/mL) and those with normal concentrations (<15 ng/mL). However, progression-free survival differed significantly (P = 0.043) according to whether the patient's HER2/neu concentration at 2 to 4 weeks after the start of therapy was >77% or ≤ 77% of her baseline concentration. The median progression-free survival times for these two groups were 217 and 587 days, respectively. A similar trend was observed for a subcohort of patients treated specifically with a combination of trastuzumab and taxane.

Conclusion

These findings indicate that serum HER2/neu testing is clinically valuable in monitoring metastatic breast cancer patients undergoing trastuzumab-based treatment and provides additional value over the commonly used CA15-3 test. The percentage of baseline HER2/neu concentrations in the early weeks after the start of therapy may be an early predictor of progression-free-survival.
High-frequency oscillatory ventilation in children: a single-center experience of 53 cases
Authors: Slee-Wijffels Fieke YAM , van der Vaart Klara RM , Twisk Jos WR , Markhorst Dick G , Plötz Frans B
Published: April 2005

Introduction

The present article reports our experience with high-frequency oscillatory ventilation (HFOV) in pediatric patients who deteriorated on conventional mechanical ventilation.

Methods

The chart records of 53 consecutively HFOV-treated patients from 1 January 1998 to 1 April 2004 were retrospectively analyzed. The parameters of demographic data, cause of respiratory insufficiency, Pediatric Index of Mortality score, oxygenation index and PaCO2 were recorded and calculated at various time points before and after the start of HFOV, along with patient outcome and cause of death.

Results

The overall survival rate was 64%. We observed remarkable differences in outcome depending on the cause of respiratory insufficiency; survival was 56% in patients with diffuse alveolar disease (DAD) and was 88% in patients with small airway disease (SAD). The oxygenation index was significantly higher before and during HFOV in DAD patients than in SAD patients. The PaCO2 prior to HFOV was higher in SAD patients compared with DAD patients and returned to normal values after the initiation of HFOV.

Conclusion

HFOV rescue therapy was associated with a high survival percentage in a selected group of children. Patients with DAD primarily had oxygenation failure. Future studies are necessary to evaluate whether the outcome in this group of patients may be improved if HFOV is applied earlier in the course of disease. Patients with SAD primarily had severe hypercapnia and HFOV therapy was very effective in achieving adequate ventilation.
Effects of abnormal cytoskeletal structure on erythrocyte membrane mechanical properties
Authors: Waugh Richard E.
Published: April 2005

Measurements of the mechanical properties of the erythrocyte membrane provide a direct assessment of the proper function of its structural components. To assess the effects of alterations in molecular structure on membrane mechanical properties, measurements have been performed on cells from six individuals whose membranes contain inherited, biochemically characterized structural defects. Because the contribution of the memmbrane skeleton to the mechanical behavior of the membrane is most evident in shear deformation, mechanical experiments were performed to measure the material constants which characterize the response of the membrane to shear force resultants. The surface elastic shear modulus characterizes the elastic response of the membrane; the yield shear resultant is the maximum shear force resultant which the membrane can support elastically; and the plastic viscosity coefficient characterizes the rate of membrane deformation when the elastic limit has been exceeded.

Generally, it was found that when the molecular defect is found to occur in a region of the skeleton which is stress‐supporting, the maximum elastic strength of the membrane is reduced. However, the magnitude of the reduction can be quite different for membranes having similar or even identical defects. In some cases the differences can be attributed to the removal of the most fragile cells of the population by the spleen, but other results indicate that the biochemical description of the defects may be incomplete. These results emphasize the need for further refinements both in the biochemical characterization of membrane skeleton structure and in the description and measurement of membrane mechanical properties.
Extension of filopodia by motor‐dependent actin assembly
Authors: Sheetz Michael P. , Wayne Denise B. , Pearlman Alan L.
Published: April 2005

A variety of mechanisms have been proposed to explain the forward extension of cytoplasm in advancing cells and axonal growth cones, including actin polymerization and osmotic swelling. Based on our observations of the filopodia of cultured neuronal growth cones, we propose a mechanism involving motor‐induced extension and retraction. We observed that filopodia (actin‐based protrusions 0.2–0.5 μ in diameter) extend and retract from growth cone lamellae at the same rate. Further, force is generated at the tips of filopodia which is sufficient to produce compressive buckling of the proximal portion of the filopodium. From our analysis of these movements we suggest that a motor protein powers both the extension and retraction of filopodia. © 1992 Wiley‐Liss, Inc.
Editorial: Electrophoresis 7‐8/2005
Authors: Schmitt‐Kopplin Phillipe
Published: April 2005

No abstracts.
TX‐1877, a bifunctional hypoxic cell radiosensitizer, enhances anticancer host response: Immune cell migration and nitric oxide production
Authors: Oshikawa Tetsuya , Okamoto Masato , Ahmed Sharif U. , Furuichi Sachiko , Tano Tomoyuki , Sasai Akiko , Kan Shin , Kasai Soko , Uto Yoshihiro , Nagasawa Hideko , Hori Hitoshi , Sato Mitsunobu
Published: April 2005

We investigated in the current study the effect of TX‐1877, a bifunctional hypoxic cell radiosensitizer, in augmenting anticancer host response. In the syngeneic squamous cell carcinoma‐bearing mouse model, a single administration of TX‐1877 significantly inhibited the primary tumor growth as well as lung metastasis. TX‐1877 administration resulted in a significant infiltration of immune cells, such as CD4+T, CD8+T cells, macrophages and dendritic cells (DCs), and an increased expression of chemokines for cytotoxic T lymphocytes (CTLs), helper T‐cell 1 (Th1) cells, monocytes/macrophages and DCs, in tumor tissues. Nitric oxide (NO) production and the expression of inducible NO synthase (iNOS) and interferon‐γ, a major Th1 cytokine that plays a major role in anticancer immunity, were also enhanced. Furthermore, neutralization of NO by N‐monomethyl‐L‐arginine acetate resulted in a marked inhibition of the antitumor effect of TX‐1877. In tumor‐draining lymph nodes, MHC class I‐restricted CD8+ memory CTLs specific for inoculated cancer cells were induced by TX‐1877. In in vitro experiments, TX‐1877 induced chemokines and iNOS/NO in several types of culture cells. These findings strongly suggested that TX‐1877 induces migration of CD8+CTLs, CD4+Th1 cells, macrophage/monocytes and dendritic cells into the tumor site, and that this migration is mediated by chemokine induction. In addition, it was suggested that NO produced by several types of cells stimulated by TX‐1877 in the tumor sites plays a major role in the anticancer effect of TX‐1877. TX‐1877 was thus shown to be an effective immunopotentiator as well as a hypoxic cell radiosensitizer. © 2005 Wiley‐Liss, Inc.
COX‐2 inhibitors suppress integrin α5 expression in human lung carcinoma cells through activation of Erk: Involvement of Sp1 and AP‐1 sites
Authors: Han ShouWei , Roman Jesse
Published: April 2005

Tumor cell expression of COX‐2 has been implicated in the progression of murine and human lung cancer. Inhibition of COX‐2 by nonsteroidal antiinflammatory drugs reduces the risk of cancer development in humans and suppresses tumor growth in animal models. However, the underlying mechanisms for this beneficial effect are not fully understood. Here we explore the potential link between the anticancer effects of COX‐2 inhibitors and the expression of the integrin α5β1. Expression of this integrin in carcinoma cells is associated with invasiveness and malignant progression. This, together with our studies showing that fibronectin, the ligand of α5β1, stimulates the growth of human lung carcinoma cells, and that this effect is mediated through α5β1‐dependent signals, has prompted us to examine the effects of COX‐2 inhibitors on α5β1 expression in human non small cell lung carcinoma (NSCLC) cells. We found that the selective COX‐2 inhibitors NS398 and Nimesulide decreased mRNA expression and protein production of the integrin α5 subunit. This effect was associated with inhibition of NSCLC cell adhesion to fibronectin. The COX‐2 inhibitors triggered the phosphorylation of extracellular signal‐regulated kinase (Erk) in a time‐dependent manner, and the inhibitor of Mek‐1/Erk PD98095 prevented their inhibitory effects on integrin α5 expression. Transient transfection assays showed that the COX‐2 inhibitors affected integrin α5 gene transcription by acting between −92 to −41 bp of the human integrin α5 gene promoter. Gel mobility shift assays showed that the COX‐2 inhibitors increased Sp1 DNA binding, but decreased that of AP‐1. These effects were accompanied by an increase in Sp1 protein and a decrease in c‐Jun protein expression, as well as inhibition of SAPK/JNK phosphorylation. The Sp1 inhibitor, Mithramycin A, also blocked the inhibitory effect of the COX‐2 inhibitors on α5 expression and promoter activity. Overall, these findings suggest that COX‐2 inhibitors suppress α5β1 integrin expression in NSCLC through effects on integrin α5 gene transcription mediated by Erk activation, increased Sp1, decreased AP‐1 DNA binding and inactivation of SAPK/JNK signals. Our observations unveil a new mechanism of action against NSCLC for COX‐2 inhibitors that relates to regulation of integrin α5 gene expression and, consequently, recognition of extracellular matrices (i.e., fibronectin) by tumor cells. © 2005 Wiley‐Liss, Inc.
Viral infections in the acquired immunodeficiency syndrome
Authors: Miller Sara E. , Howell David N.
Published: April 2005

The following communication is a tripartite synopsis of the role of viral infection in the acquired immunodeficiency syndrome (AIDS). The first section describes the impact of viral opportunistic infection in AIDS; for each virus, clinical presentation and diagnosis, laboratory diagnostic approaches (with emphasis on electron microscopy), and therapeutic interventions attempted to date are discussed. The second segment explores current theories on the pathogenesis of AIDS, and describes diagnostic and therapeutic approaches to the syndrome itself. The final section catalogues ultrastructural anomalies in the cells of AIDS patients, many of which have been mistakenly identified as etiologic agents.
Early apoptotic and late necrotic components associated with altered Ca2+ homeostasis in a peptide‐delivery model of polyglutamine‐induced neuronal death
Authors: Suzuki Mari , Koike Tatsuro
Published: April 2005

The mechanisms by which polyglutamine expansion causes common features of neuronal death remain unclear. Here we describe an approach for delivering polyglutamine expansions directly into cultured sympathetic neurons. Glutamine (Q) residues (n = 10, 22, 30) were conjugated with a peptide possessing translocation properties across plasma membranes (PDP) and a nuclear localization signal (NLS). These peptides were rapidly incorporated into sympathetic neurons and showed neurotoxicity in a length‐ and dose‐dependent manner. A robust induction of c‐jun and cyclin D1 occurred following treatment with PDP‐Q22‐NLS. Enhanced c‐Jun phosphorylation showed c‐Jun N‐terminal kinase (JNK) activation. Coincidentally, TrkA tyrosine phosphorylation was decreased in association with loss of phospho‐Akt, the downstream target of PI‐3 kinase. Despite such proapoptotic signals, neither release of cytochrome c from mitochondria nor caspase‐3/7 activation was detected. TdT‐mediated dUTP nick‐end labeling‐positive nuclear condensation, but no fragmentation, occurred. At 24 hr of treatment, cytoplasmic Ca2+ levels began to become elevated, and the cellular level of ATP was decreased. Cytoplasmic Ca2+ responses to KCl depolarization displayed a delayed recovery, providing evidence for lack of Ca2+ homeostasis. The neurons became committed to death at about 36 hr when mitochondrial Ca2+ uptake declined concurrently with loss of mitochondrial membrane potential. Collectively, these results show that, despite induction of early apoptotic signals, nonapoptotic neuronal cell death occurred via perturbed Ca2+ homeostasis and suggest that mitochondrial permeability transition may play important roles in this model of neuronal death. © 2005 Wiley‐Liss, Inc.
Dual‐band LTCC chip antenna design using stacked meander patch for mobile handsets
Authors: Kim Young Do , Kim Ho‐Yong , Lee Hong Min
Published: April 2005

This paper presents design simulation, implementation, and measurement of a miniaturized GPS/K‐PCS dual‐band LTCC chip antenna for mobile communication handsets. The dimensions of the LTCC chip antenna is 9 × 15 × 1.2 mm. The meander‐type radiating patch for dual‐band operation is realized by using via holes with 0.3‐mm height to connect upper‐ and lower‐layer antennas. The lower meander‐type antenna is to be tuned to the lower frequency (GPS) band. The upper meander antenna has a via‐hole connection for the higher frequency (K‐PCS) band. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 271–273, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20793
A wideband circularly polarized microstrip patch antenna for 5–6‐GHz wireless LAN applications
Authors: Yang G. , Ali M. , Dougal R.
Published: April 2005

A wideband slotted circularly polarized (CP) patch antenna is introduced for 5–6‐GHz WLAN applications. A small 14.6 × 14.6 mm square patch on Duroid 5880 substrate can provide a return‐loss bandwidth of 11% and an axial‐ratio bandwidth of 8% with a single feed. A possible reconfigurable design achievable using PIN diode or MEMS switches capable of left‐hand or right‐hand circular polarization is also introduced. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 279–285, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20796
23‐GHz low‐noise amplifier using parallel feedback in 0.18‐μm CMOS
Authors: Frank B. M. , Hossain M. M. , Antar Y. M. M.
Published: April 2005

A three‐stage low‐noise amplifier (LNA) fabricated in a standard 0.18‐μm CMOS process (fT= 45 GHz) with a maximum gain of 18 dB at 23.2 GHz and a 5.8‐dB noise figure is presented. Parallel feedback between the gate and drain is used in all three stages. This configuration also provides much better linearity than other LNAs presented by resonating out the effect ofCgd. The amplifier has an output‐referred 3rd‐order intercept of 10 dBm, and a 3‐dB bandwidth of approximately 1 GHz. This paper demonstrates that parallel feedback is a viable technique for the design of 20+‐GHz CMOS LNAs. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 309–312, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20806
Implicit nonstaggered finite‐difference time‐domain method
Authors: Wang Shumin , Lee Robert , Teixeira Fernando L.
Published: April 2005

A new, unconditionally stable, implicit nonstaggered finite‐difference time‐domain (INS‐FDTD) method is introduced. This method is more efficient than the (unconditionally stable) finite‐element time‐domain (FETD) method with brick elements because the number of nonzero elements in the system matrix is reduced. A numerical‐dispersion analysis is provided as well. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 317–319, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20809
Modal analysis of dielectric optical waveguides based on Chebyshev polynomials
Authors: Huang Chia‐Chien , Huang Chia‐Chih
Published: April 2005

We propose an accurate and efficient numerical method to compute the modal characteristics of dielectric optical waveguides. The present method represents electric and/or magnetic fields by Chebyshev polynomials based on a multidomain spectral collocation scheme. Compared with analytical solutions and the published results using rigorous numerical methods, our results show excellent agreement. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 328–331, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20813
Experimental validation of OSNR enhancement utilizing hybrid Raman/Erbium fiber amplifiers
Authors: Ahmad A. , Mas Izyani M. A. , Zamzuri A. K. , Adikan F. R. M. , Sheih S‐J. , Mahdi M. A.
Published: April 2005

The impact of employing a hybrid Raman/Erbium‐doped fiber amplifier (EDFA) in a transmission system is demonstrated by considering the optical signal‐to‐noise ratio (OSNR) performance. The gain flatness of hybrid Raman/EDFA is maintained below 1.2 dB from 1530 to 1565 nm through careful design of both amplifiers. The enhancement of OSNR is measured at around 5 dB, compared to the conventional EDFA approach with a 28‐dB span loss. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 333–335, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20815
Construction of refractive‐index profiles of graded‐index planar waveguides from effective indexes measured with different mode types and external refractive indexes
Authors: Wei J. , Xu X.‐F. , Kang Z.‐H. , Jiang Y. , Ding Y. , Gao J.‐Y.
Published: April 2005

A method is presented whereby the refractive‐index profile (RIP) can be reconstructed from sets of effective indexes measured with different mode types and external refractive indexes. Single‐mode waveguide RIP characterization can be easily realized using an index‐matching liquid at a single wavelength. This method is described and demonstrated via numerical examples and experimental results. The method has the advantages of convenient operation and accurate results for the characterization of graded‐index planar waveguides that support both mode types and contain known modal birefringence. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 342–345, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20818
Probe‐fed center‐slotted suspended plate antennas with resistive and capacitive loadings
Authors: Chen Zhi Ning , Ng Jin Hau
Published: April 2005

This paper presents the probe‐fed center‐slotted suspended plate antennas (CS‐SPAs) with capacitive and resistive loading. The impedance and radiation characteristics of the proposed antennas, such as impedance bandwidth, gain, radiation patterns, and cross‐pol radiation levels are investigated. The simulated results are validated by the measurements and compared with three other CS‐SPAs fed by a single probe, short‐circuited, and open‐circuited loading, respectively. This study demonstrates an enhancement of impedance bandwidth and a decrease in gain with resistive loading, as compared to the CS‐SPA with a shorting pin. The gains of CS‐SPAs with plate‐capacitor loading generally increase, with the same impedance bandwidth as that of the CS‐SPA with a shorting pin. © 2005 Wiley Periodicals, Inc. Microwave Opt Technol Lett 45: 355–360, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20822