bluuebunny/crossref_metadata_2025 huggingface dataset:
Hidden Morbidity in Cancer: Spouse Caregivers
Authors: Braun Michal , Mikulincer Mario , Rydall Anne , Walsh Andrew , Rodin Gary
Published: October 2007

Purpose

This study assesses psychological distress among advanced cancer patients and their spouse caregivers, while examining the relative contribution of caregiving burden and relational variables (attachment orientation and marital satisfaction) to depressive symptoms in the spouse caregivers.

Methods

A total of 101 patients with advanced GI or lung cancer and their spouse caregivers were recruited for the study. Measures included Beck Depression Inventory–II (BDI-II), Caregiving Burden scale, Experiences in Close Relationships scale, and ENRICH Marital Satisfaction scale.

Results

A total of 38.9% of the caregivers reported significant symptoms of depression (BDI-II ≥ 15) compared with 23.0% of their ill spouses (P < .0001). In a hierarchical regression predicting caregiver's depression, spouse caregiver's age and patient's cancer site were entered in the first step, objective caregiving burden was entered in the second step, subjective caregiving burden was entered in the third step, caregiver's attachment scores were entered in the fourth step, and caregiver's marital satisfaction score was entered in the fifth step. The final model accounted for 37% of the variance of caregiver depression, with subjective caregiving burden (β = .38; P < .01), caregiver's anxious attachment (β = .21; P < .05), caregiver's avoidant attachment (β = .20; P < .05), and caregiver's marital satisfaction (β = −.18; P < .05) making significant contributions to the model.

Conclusion

Spouse caregivers of patients with advanced cancer are a high-risk population for depression. Subjective caregiving burden and relational variables, such as caregivers' attachment orientations and marital dissatisfaction, are important predictors of caregiver depression.
Randomized, Controlled Trial of Irinotecan Plus Infusional, Bolus, or Oral Fluoropyrimidines in First-Line Treatment of Metastatic Colorectal Cancer: Results From the BICC-C Study
Authors: Fuchs Charles S. , Marshall John , Mitchell Edith , Wierzbicki Rafal , Ganju Vinod , Jeffery Mark , Schulz Joseph , Richards Donald , Soufi-Mahjoubi Raoudha , Wang Benjamin , Barrueco José
Published: October 2007

Purpose

This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI).

Patients and Methods

A total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity.

Results

Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of ≥ grade 3 hypertension than mIFL+Bev.

Conclusion

FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.
Phase I Study of Everolimus in Pediatric Patients With Refractory Solid Tumors
Authors: Fouladi Maryam , Laningham Fred , Wu Jianrong , O'Shaughnessy Melinda A. , Molina Kristen , Broniscer Alberto , Spunt Sheri L. , Luckett Inga , Stewart Clinton F. , Houghton Peter J. , Gilbertson Richard J. , Furman Wayne L.
Published: October 2007

Purpose

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetic and pharmacodynamic properties of the mammalian target of rapamycin (mTOR) inhibitor, everolimus, in children with refractory or recurrent solid tumors.

Patients and Methods

Everolimus was administered orally at a daily dose of 2.1, 3, 5, or 6.5 mg/m2in cohorts of three to six patients per dosage level. Pharmacokinetic and pharmacodynamic studies were performed during the first course. The phosphorylation status of various components of the mTOR signal pathway was assessed in peripheral-blood mononuclear cells (PBMCs) isolated from treated patients.

Results

There were 26 patients enrolled; 18 were assessable. DLTs included diarrhea (n = 1), mucositis (n = 1), and elevation of ALT (n = 1) at 6.5 mg/m2. At the MTD of 5 mg/m2, the median everolimus clearance was 15.2 L/h/m2, with a plasma everolimus concentration-time area under the curve (AUC) from 0 to infinity of 239.6 ng/mL·h. Significant inhibition of mTOR pathway signaling was observed in PBMCs from patients achieving AUCs ≥ 200 ng/mL·h, equivalent to dosages of 3 to 5 mg/m2of everolimus. No objective tumor responses were observed.

Conclusion

Continuous, orally administered everolimus is well tolerated in children with recurrent or refractory solid tumors and demonstrates similar pharmacokinetic properties to those observed in adults. Everolimus significantly inhibits the mTOR signaling pathway in children at the MTD. The recommended phase II dose in children with solid tumors is 5 mg/m2.
Carbonic Anhydrase IX Is Not an Independent Predictor of Outcome for Patients With Clear Cell Renal Cell Carcinoma
Authors: Leibovich Bradley C. , Sheinin Yuri , Lohse Christine M. , Thompson R. Houston , Cheville John C. , Zavada Jan , Kwon Eugene D.
Published: October 2007

Purpose

Expression of carbonic anhydrase IX (CAIX) has been reported to be an independent predictor of outcome and is being investigated as a therapeutic target for patients with clear cell renal cell carcinoma (ccRCC). We attempted to validate the prognostic utility of CAIX expression using a large cohort of ccRCC patients with long-term follow-up.

Patients and Methods

We identified 730 patients with unilateral, sporadic ccRCC treated surgically between 1990 and 1999. Anti-CAIX monoclonal antibody (clone M75) was used, and tumor specimens were blindly scored for expression levels. Associations of CAIX expression with RCC death were evaluated using Cox proportional hazards regression models.

Results

There were 241 RCC deaths and a median of 9.4 years of follow-up for patients still under observation. CAIX was expressed in 708 (97.0%) of the specimens; 163 tumors (22.3%) exhibited low (≤ 85% tumor cells positive) expression, and 567 (77.7%) exhibited high (> 85% tumor cells positive) expression. Univariately, low CAIX expression was associated with increased risk of RCC death relative to high expression (risk ratio = 1.65; P < .001). However, low CAIX expression was not associated with RCC death after adjusting for nuclear grade or coagulative tumor necrosis. Additionally, we observed CAIX expression in a number of extrarenal organs.

Conclusion

CAIX is strongly expressed by ccRCC. Although CAIX is associated with outcome in patients with ccRCC, it is not an independent prognostic marker. Furthermore, CAIX expression is apparent in extrarenal organs. As such, exploitation of CAIX as a prognostic marker and therapeutic target merits additional consideration.
Phase II Trial of Sunitinib in Patients With Metastatic Colorectal Cancer After Failure of Standard Therapy
Authors: Saltz Leonard B. , Rosen Lee S. , Marshall John L. , Belt Robert J. , Hurwitz Herbert I. , Eckhardt S. Gail , Bergsland Emily K. , Haller Daniel G. , Lockhart A. Craig , Rocha Lima Caio M. , Huang Xin , DePrimo Samuel E. , Chow-Maneval Edna , Chao Richard C. , Lenz Heinz J.
Published: October 2007

Purpose

Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor of the vascular endothelial growth factor receptor and multiple other growth factor receptors. We assessed the safety and efficacy of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy.

Patients and Methods

Eighty-four patients were enrolled onto this two-stage phase II trial and were stratified by whether they had received prior bevacizumab (n = 43) or not (n = 41). Treatment comprised sunitinib 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles.

Results

By Response Evaluation Criteria in Solid Tumors criteria, one patient, who was in the prior bevacizumab cohort, achieved a partial response, and 13 patients (two in the prior bevacizumab cohort and 11 in the no prior bevacizumab cohort) achieved stable disease lasting ≥ 22 weeks. Median time to progression in the prior bevacizumab and bevacizumab-naïve cohorts was 2.2 months (95% CI, 1.9 to 2.3 months) and 2.5 months (95% CI, 2.3 to 3.1 months), respectively, whereas median overall survival time was 7.1 months (95% CI, 4.9 to 10.6 months) and 10.2 months (95% CI, 8.2 to 15.3 months), respectively. The most common adverse events were fatigue, diarrhea, nausea, vomiting, and anorexia. Twenty-six patients (32%) required dose reduction to 37.5 mg/d, and one patient required dose reduction to 25 mg/d.

Conclusion

Sunitinib did not demonstrate a meaningful single-agent objective response rate in colorectal cancer refractory to standard chemotherapy. However, the mechanisms of action and acceptable safety profile of sunitinib warrant further study in combination with standard regimens for metastatic colorectal cancer.
Estradiol Regulates Corticotropin-Releasing Hormone Gene (crh) Expression in a Rapid and Phasic Manner that Parallels Estrogen Receptor-α and -β Recruitment to a 3′,5′-Cyclic Adenosine 5′-Monophosphate Regulatory Region of the Proximal crh Promoter
Authors: Lalmansingh Avin S. , Uht Rosalie M.
Published: October 2007

In the central nervous system, CRH regulates several affective states. Dysregulation of neuronal crh expression in the paraventricular nucleus of the hypothalamus correlates with some forms of depression, and amygdalar crh expression may modulate levels of anxiety. Because estrogens modulate these states, we sought to determine 17β-estradiol (E2) effects on crh expression. CRH mRNA levels were measured in the AR-5 amygdaloid cell line by RT-PCR analysis. They increased by 1 min of E2 treatment, suggesting that crh behaves as an immediate-early gene. After peaking at 3 min, CRH mRNA returned to basal levels and then increased by 60 min. To dissect some of the molecular mechanisms underlying these events, we measured occupancy of the crh promoter by estrogen receptors (ERs) and coactivators, using chromatin immunoprecipitation. Because this promoter does not contain palindromic estrogen response elements, we targeted the region of a cAMP regulatory element (CRE), implicated in crh regulation. The temporal pattern of the mRNA response was mimicked by recruitment of ERα and -β, phospho-CRE-binding protein, coactivators steroid receptor coactivator-1 and CRE-binding protein-binding protein (CBP), and an increase in histone 3 and 4 acetylation. Lastly, ERα and -β loading were temporally dissociated, peaking at 1 and 3 min, respectively. The ER peaks were associated with coactivators and acetylation patterns. ERα associated with phospho-CRE-binding protein, CBP, steroid receptor coactivator-1, and increased acetylated histone 3. ERβ associated with CBP and increased acetylated histone 4. The tight temporal correlation between E2-induced CRH mRNA levels and promoter occupancy by ERs strongly suggest that E2 regulates crh expression through an ERα- and/or ERβ-CRE alternate pathway.
SH2B1β (SH2-Bβ) Enhances Expression of a Subset of Nerve Growth Factor-Regulated Genes Important for Neuronal Differentiation Including Genes Encoding Urokinase Plasminogen Activator Receptor and Matrix Metalloproteinase 3/10
Authors: Chen Linyi , Maures Travis J. , Jin Hui , Huo Jeffrey S. , Rabbani Shafaat A. , Schwartz Jessica , Carter-Su Christin
Published: October 2007

Previous work showed that the adapter protein SH2B adapter protein 1β (SH2B1) (SH2-B) binds to the activated form of the nerve growth factor (NGF) receptor TrkA and is critical for both NGF-dependent neurite outgrowth and maintenance. To identify SH2B1β-regulated genes critical for neurite outgrowth, we performed microarray analysis of control PC12 cells and PC12 cells stably overexpressing SH2B1β (PC12-SH2B1β) or the dominant-negative SH2B1β(R555E) [PC12-SH2B1β(R555E)]. NGF-induced microarray expression of Plaur and Mmp10 genes was greatly enhanced in PC12-SH2B1β cells, whereas NGF-induced Plaur and Mmp3 expression was substantially depressed in PC12-SH2B1β(R555E) cells. Plaur, Mmp3, and Mmp10 are among the 12 genes most highly up-regulated after 6 h of NGF. Their protein products [urokinase plasminogen activator receptor (uPAR), matrix metalloproteinase 3 (MMP3), and MMP10] lie in the same pathway of extracellular matrix degradation; uPAR has been shown previously to be critical for NGF-induced neurite outgrowth. Quantitative real-time PCR analysis revealed SH2B1β enhancement of NGF induction of all three genes and the suppression of NGF induction of all three when endogenous SH2B1 was reduced using short hairpin RNA against SH2B1 and in PC12-SH2B1β(R555E) cells. NGF-induced levels of uPAR and MMP3/10 and neurite outgrowth through Matrigel (MMP3-dependent) were also increased in PC12-SH2B1β cells. These results suggest that SH2B1β stimulates NGF-induced neuronal differentiation at least in part by enhancing expression of a specific subset of NGF-sensitive genes, including Plaur, Mmp3, and/or Mmp10, required for neurite outgrowth.
Co-regulation by Notch and Fos is required for cell fate specification of intermediate precursors duringC. elegansuterine development
Authors: Oommen Kavita S. , Newman Anna P.
Published: October 2007

The Notch pathway is the key signal for many cell fate decisions in the nematode Caenorhabditis elegans including the uterine π cell fate,crucial for a proper uterine-vulval connection and egg laying. Expression of the egl-13 SOX domain transcription factor is specifically upregulated upon induction of the π lineage and not in response to other LIN-12/Notch-mediated decisions. We determined that dual regulation by LIN-12 and FOS-1 is required for egl-13 expression at specification and for complete rescue of egl-13 mutants. We found that fos-1mutants exhibit uterine defects and fail to express π markers. We show that FOS-1 is expressed at π cell specification and can bind in vitro to egl-13 upstream regulatory sequence (URS) as a heterodimer with C. elegans Jun.
TheC. elegansROR receptor tyrosine kinase, CAM-1,non-autonomously inhibits the Wnt pathway
Authors: Green Jennifer L. , Inoue Takao , Sternberg Paul W.
Published: October 2007

Inhibitors of Wnt signaling promote normal development and prevent cancer by restraining when and where the Wnt pathway is activated. ROR proteins, a class of Wnt-binding receptor tyrosine kinases, inhibit Wnt signaling by an unknown mechanism. To clarify how RORs inhibit the Wnt pathway, we examined the relationship between Wnts and the sole C. elegans ROR homolog, cam-1, during C. elegans vulval development, a Wnt-regulated process. We found that loss and overexpression of cam-1 causes reciprocal defects in Wnt-mediated cell-fate specification. Our molecular and genetic analyses revealed that the CAM-1 extracellular domain (ECD) is sufficient to non-autonomously antagonize multiple Wnts, suggesting that the CAM-1/ROR ECD sequesters Wnts. A sequestration model is supported by our findings that the CAM-1 ECD binds to several Wnts in vitro. These results demonstrate how ROR proteins help to refine the spatial pattern of Wnt activity in a complex multicellular environment.
BMP signaling regulates the dorsal planarian midline and is needed for asymmetric regeneration
Authors: Reddien Peter W. , Bermange Adam L. , Kicza Adrienne M. , Sánchez Alvarado Alejandro
Published: October 2007

Planarians can be cut into irregularly shaped fragments capable of regenerating new and complete organisms. Such regenerative capacities involve a robust ability to restore bilateral symmetry. We have identified three genes needed for bilaterally asymmetric fragments to regenerate missing body parts. These genes are candidate components of a signaling pathway that controls the dorsal-ventral patterning of many animal embryos: a BMP1/Tolloid-like gene(smedolloid-1), a SMAD4-like gene (smedsmad4-1), and a BMP2/4/DPP-like gene (smedbmp4-1). BMP signaling was involved in the formation of new tissues at the midline of regeneration, the dorsal-ventral patterning of new tissues, and the maintenance of the dorsal-ventral pattern of existing adult tissue in homeostasis. smedbmp4-1 was normally expressed at the dorsal midline. Asymmetric fragments lacking a midline displayed new smedbmp4-1 expression prior to formation of a regenerative outgrowth (blastema). Asymmetric fragments containing the midline displayed expanded smedbmp4-1 expression towards the wound. We suggest injured animals that lack left-right symmetry reset their midline through modulation of BMP activity as an early and necessary event in regeneration.
Axonal wiring of guanylate cyclase-D-expressing olfactory neurons is dependent on neuropilin 2 and semaphorin 3F
Authors: Walz Andreas , Feinstein Paul , Khan Mona , Mombaerts Peter
Published: October 2007

The olfactory system of the mouse includes several subsystems that project axons from the olfactory epithelium to the olfactory bulb. Among these is a subset of neurons that do not express the canonical pathway of olfactory signal transduction, but express guanylate cyclase-D (GC-D). These GC-D-positive (GC-D+) neurons are not known to express odorant receptors. Axons of GC-D+ neurons project to the necklace glomeruli, which reside between the main and accessory olfactory bulbs. To label the subset of necklace glomeruli that receive axonal input from GC-D+ neurons, we generated two strains of mice with targeted mutations in the GC-D gene (Gucy2d). These mice co-express GC-D with an axonal marker, tau-β-galactosidase or tauGFP, by virtue of a bicistronic strategy that leaves the coding region of the Gucy2d gene intact. With these strains, the patterns of axonal projections of GC-D+ neurons to necklace glomeruli can be visualized in whole mounts. We show that deficiency of one of the neuropilin 2 ligands of the class III semaphorin family, Sema3f, but not Sema3b, phenocopies the loss of neuropilin 2 (Nrp2) for axonal wiring of GC-D+ neurons. Some glomeruli homogeneously innervated by axons of GC-D+ neurons form ectopically within the glomerular layer, across wide areas of the main olfactory bulb. Similarly, axonal wiring of some vomeronasal sensory neurons is perturbed by a deficiency of Nrp2 or Sema3f, but not Sema3b or Sema3c. Our findings provide genetic evidence for a Nrp2-Sema3f interaction as a determinant of the wiring of axons of GC-D+ neurons into the unusual configuration of necklace glomeruli.
A key role ofPox mesoin somatic myogenesis ofDrosophila
Authors: Duan Hong , Zhang Cheng , Chen Jianming , Sink Helen , Frei Erich , Noll Markus
Published: October 2007

The Pax gene Pox meso (Poxm) was the first and so far only gene whose initial expression was shown to occur specifically in the anlage of the somatic mesoderm, yet its role in somatic myogenesis remained unknown. Here we show that it is one of the crucial genes regulating the development of the larval body wall muscles in Drosophila. It has two distinct functions expressed during different phases of myogenesis. The early function, partially redundant with the function of lethal of scute[l(1)sc], demarcates the `Poxm competence domain', a domain of competence for ventral and lateral muscle development and for the determination of at least some adult muscle precursor cells. The late function is a muscle identity function, required for the specification of muscles DT1,VA1, VA2 and VA3. Our results led us to reinterpret the roles of l(1)sc and twist in myogenesis and to propose a solution of the `l(1)sc conundrum'.
Hox gene function in vertebrate gut morphogenesis: the case of the caecum
Authors: Zacchetti Giovanna , Duboule Denis , Zakany Jozsef
Published: October 2007

The digestive tract is made of different subdivisions with various functions. During embryonic development, the developing intestine expresses combinations of Hox genes along its anterior to posterior axis, suggesting a role for these genes in this regionalization process. In particular, the transition from small to large intestine is labelled by the transcription of all Hoxd genes except Hoxd12 and Hoxd13, the latter two genes being transcribed only near the anus. Here, we describe two lines of mice that express Hoxd12 ectopically within this morphological transition. As a consequence, budding of the caecum is impeded, leading to complete agenesis in homozygous individuals. This effect is concurrent with a dramatic reduction of both Fgf10 and Pitx1 expression. Furthermore, the interactions between `anterior' Hox genes and ectopic Hoxd12 suggest a model whereby anterior and posterior Hox products compete in controlling Fgf10 signalling, which is required for the growth of this organ in mice. These results illuminate components of the genetic cascade necessary for the emergence of this gut segment, crucial for many vertebrates.
Coordinated contractions effectively expel water from the aquiferous system of a freshwater sponge
Authors: Elliott Glen R. D. , Leys Sally P.
Published: October 2007

In response to mechanical stimuli the freshwater sponge Ephydatia muelleri (Demospongiae, Haplosclerida, Spongillidae) carries out a series of peristaltic-like contractions that is effective in expelling clumps of waste material from the aquiferous system. Rates of contraction depend on the region of tissue they are propagating through: 0.3–1 μm s–1 in the peripheral canals, 1–4 μm s–1 in central canals, and 6–122 μm s–1 in the osculum. Faster events include twitches of the entire sponge choanosome and contraction of the sheet-like apical pinacoderm that forms the outer surface of the animal. Contraction events are temporally and spatially coordinated. Constriction of the tip of the osculum leads to dilation of excurrent canals; fields of ostia in the apical pinacoderm close in unison just prior to contraction of the choanosome, apical pinacoderm and osculum. Relaxation returns the osculum, canals and the apical pinacoderm to their normal state, and three such coordinated `inflation–contraction'responses typically follow a single stimulus. Cells in the mesohyl arrest crawling as a wave of contraction passes, suggesting an extracellular signal may pass between cells. Bundles of actin filaments traverse endopinacocytes of the apical pinacoderm. Actin-dense plaques join actin bundles in adjacent pinacocytes to form continuous tracts spanning the whole sponge. The orchestrated and highly repeatable series of contractions illustrates that cellular sponges are capable of coordinated behavioural responses even in the absence of neurons and true muscle. Propagation of the events through the pinacocytes also illustrates the presence of a functional epithelium in cellular sponges. These results suggest that control over a hydrostatic skeleton evolved prior to the origin of nerves and true muscle.
Allometric scaling in centrarchid fish: origins of intra- and inter-specific variation in oxidative and glycolytic enzyme levels in muscle
Authors: Davies Rhiannon , Moyes Christopher D.
Published: October 2007

The influence of body size on metabolic rate, muscle enzyme activities and the underlying patterns of mRNA for these enzymes were explored in an effort to explain the genetic basis of allometric variation in metabolic enzymes. We studied two pairs of sister species of centrarchid fish: black bass(largemouth bass Micropterus salmoides and smallmouth bass Micropterus dolomieui) and sunfish (pumpkinseed Lepomis gibbosus and bluegill Lepomis macrochirus). Our goal was to assess the regulatory basis of both intraspecific and interspecific variation relative to body size, as well as to gain insights into the evolutionary constraints within lineages. Whole animal routine metabolic rate showed scaling coefficients not significantly different from 1, ranging from (+0.87 to +0.96). However, there were significant effects of body size on the specific activities of oxidative and glycolytic enzymes. Mass-specific activity of the oxidative enzyme citrate synthase (CS) scaled negatively with body size in each species, with scaling coefficients ranging from –0.15 to –0.19, whereas the glycolytic enzyme pyruvate kinase (PK) showed positive scaling, with scaling coefficients ranging from +0.08 to +0.23. The ratio of mass-specific enzyme activity in PK to CS increased with body size,whereas the ratio of mRNA transcripts of PK to CS was unaffected, suggesting the enzyme relationships were not due simply to transcriptional regulation of both genes. The mass-dependent differences in PK activities were best explained by transcriptional regulation of the muscle PK gene; PK mRNA was a good predictor of PK specific enzyme activity within species and between species. Conversely, CS mRNA did not correlate with CS specific enzyme activities, suggesting post-transcriptional mechanisms may explain the observed inter-specific and intraspecific differences in oxidative enzymes.
Drosophilaflies combine periodic heartbeat reversal with a circulation in the anterior body mediated by a newly discovered anterior pair of ostial valves and `venous' channels
Authors: Wasserthal Lutz T.
Published: October 2007

Heartbeat activity in tethered adult drosophilids was recorded using a linear optosensor chip and an IR-light beam. Recording from two to five sensor elements within 250 μm along the anterior heart, it was possible to analyze periodic reversals. In intact Drosophila melanogaster and D. hydei, longer anterograde pulse periods with lower pulse rates generally alternated with shorter retrograde pulse periods having higher pulse rates. These differences are dependent on heart anatomy: a newly discovered first pair of ostia is connected to bilateral thoraco-abdominal hemolymph channels. These channels are part of a venous space separated from the abdominal hemocoel by a septum, consisting of a metanotal ridge and the pericardial diaphragm lined by a special form of fat body. The channels are sealed, and their lumen is possibly controlled by the metathoracic tergo-pleural muscle. During retrograde pulses, the heart chamber works like a suction pump,aspiring hemolymph through the first ostia from the venous channels and discharging it through a newly described caudal opening. During forward beating, the anterior chamber receives hemolymph via all inflow ostia from the entire heart and drives it like a pressure pump through the narrow aorta. Also, during forward pulses, a lateral circulation occurs in the thorax as a result of the venous supply. Inhibition of abdominal mobility leads to an irregular heart rate, with pulse-wise alternating heartbeat reversals. The possible involvement of slow abdominal movements in heartbeat periodicity is discussed. The heartbeat periods are superimposed with intermittent bouts of abdominal pumping movements.
An examination of the metabolic processes underpinning critical swimming in Atlantic cod (Gadus morhua L.) using in vivo31P-NMR spectroscopy
Authors: Lurman Glenn J. , Bock Christian H. , Pörtner Hans-O.
Published: October 2007

Traditionally, critical swimming speed has been defined as the speed when a fish can no longer propel itself forward, and is exhausted. To gain a better understanding of the metabolic processes at work during a Ucrit swim test, and that lead to fatigue, we developed a method using in vivo31P-NMR spectroscopy in combination with a Brett-type swim tunnel. Our data showed that a metabolic transition point is reached when the fish change from using steady state aerobic metabolism to non-steady state anaerobic metabolism, as indicated by a significant increase in inorganic phosphate levels from 0.3±0.3 to 9.5±3.4 mol g–1, and a drop in intracellular pH from 7.48±0.03 to 6.81±0.05 in muscle. This coincides with the point when the fish change gait from subcarangiform swimming to kick-and-glide bursts. As the number of kicks increased, so too did the Pi concentration, and the pHi dropped. Both changes were maximal at Ucrit. A significant drop in Gibbs free energy change of ATP hydrolysis from –55.6±1.4 to –49.8±0.7 kJ mol–1 is argued to have been involved in fatigue. This confirms earlier findings that the traditional definition of Ucrit, unlike other critical points that are typically marked by a transition from aerobic to anaerobic metabolism, is the point of complete exhaustion of both aerobic and anaerobic resources.
Application of the charge simulation method to analysis of large deflections of elastic plates
Authors: Kimura K
Published: October 2007

The non-linear Berger equation is used to obtain solutions for deformation of thin elastic plates, and is solved by applying the charge simulation method. The general solution for the deflection is first obtained by a combination of two kinds of series of Green's functions. Satisfying the boundary conditions at the collocation points, the unknown constants in the general solution are determined, and the deflection of the plate is calculated. Numerical results are presented in dimensionless graphical form for rectangular and isosceles triangular plates.
Stress wave effects in the Flying Wedge high strain rate tensile testing device
Authors: Majzoobi G. H , Barton D C , Ramezani M
Published: October 2007

Stress wave effects in the high-rate tensile testing apparatus known as the ‘Flying Wedge’ have been investigated using both experimental and numerical approaches. The experiments were conducted on R2000 glass/epoxy composites and iron specimens at strain rates up to 103/s. Numerical simulations were carried out using the LS-DYNA hydro code. Both the numerical and the experimental results showed that the results for small and low-strength specimens were significantly affected by the stress waves that propagate through the parts of the testing machine following the impact. The time period of the resulting load oscillations was found to be similar to that calculated from one-dimensional stress wave theory for different load paths in the apparatus. Therefore, it is concluded that stress wave effects play a dominant role in the Flying Wedge for small and low-strength specimens and consequently this machine is not a suitable choice for dynamic testing of such specimens.
Displacement potential approach to the solution of stiffened orthotropic composite panels under uniaxial tensile load
Authors: Deb Nath S K , Afsar A M , Reaz S Ahmed
Published: October 2007

The current paper presents an analytical method for the analysis of elastic field in a stiffened unidirectional orthotropic composite panel under uniaxial tensile load in the direction of fibres. The mixed boundary value elasticity problem is formulated in terms of a single potential function ψ, expressed in terms of the displacement components. This function satisfies one of the differential equations of equilibrium automatically. Therefore, the mixed boundary value problem is reduced to the solution of a single differential equation of equilibrium along with the associated boundary conditions. The analytical solution is obtained in the form of an infinite series. Some numerical results of different stress and displacement components at different sections of the panel are presented in the form of graphs. The reliability and soundness of the method are verified by comparing the results with finite-difference and finite-element solutions of the problem. Good agreement of the results establishes the superiority of the present analytical method based on the displacement potential function.
Comparative implementation studies of the minimal controller synthesis algorithm on an electrohydraulic actuator plant
Authors: Bulut S
Published: October 2007

Electrohydraulic servosystems have large extent of model uncertainties and generally difficult to control. The current paper studies the application of the direct adaptive minimal controller synthesis (MCS) algorithm to an electrohydraulic positioning system. Comparative implementation studies are presented of a typical servohydraulic positioning system, as used in aerospace applications. The performance of the MCS controller is evaluated through experimental and analytical studies. In order to investigate the robustness of the MCS control, the system is operated away from nominal working condition (by changing the supply pressure and/or accumulators settings) and the performances of both the MCS control and the proportional plus derivative feedback (P + DFB) controller were compared. The results show that MCS is fairly insensitive to parameter variations, unmodelled dynamics and external disturbances, yielding much better response characteristics, compared with those of a conventional P + DFB controller.
Effect of oscillation on skin friction drag under the influence of adverse pressure gradients
Authors: Amir M , Kontis K
Published: October 2007

An experimental study has been conducted to investigate the effects of streamwise oscillation at a range of Strouhal numbers (0.0006-0.0113) on the skin friction drag of a flat plate under the influence of adverse pressure gradients at subsonic speed (16 m/s). The Reynolds number was 106 based on the flat plate chord-length. A cylinder placed in the turbulent region over the flat plate within the boundary layer was used to create the effects of adverse pressure gradients. Skin friction drag was determined from the velocity gradients in the streamwise direction in the wall region of the flat plate using hotwire anemometry. Oscillation reduced skin friction drag in the turbulent region, whereas, increments in drag were measured in the separated region. The results showed higher reductions in drag at low Strouhal numbers with the strongest effect to take place at Strouhal number equal to 0.0006. With increasing Strouhal number, reductions in skin friction drag were minimized.
A node-to-node composite graph and pseudo-Boolean modelling: An unmanned aerial vehicle energy application
Authors: Economou J T , Kladis G P , Tsourdos A , White B A
Published: October 2007

Unmanned aerial vehicles (UAV) have been gaining momentum in recent years because of their vast application areas in the defence and civilian sectors. Their use can result in future missions to be more effective while also be conducted in a safer manner. UAVs, due to their large operational potential may be required to travel over long distances and prespecified way points thus requiring an effective and efficient decision making mechanism which allow the UAV to start and complete its mission. These missions may start and terminate at different or identical topological locations (or nodes). In the current paper a node-to-node graph theory energy costs modelling method is developed and presented. The modelling method requires as a priori the node-to-node energy costs. Furthermore, several propositions were presented to allow for the energy matrix to be perturbable, thus representing possible atmospheric variations which may occur during the UAVs mission. The UAV is modelled using energy graphs which allow a topological optimum to be obtained via suitable optimization algorithms. The energy costs implicitly contain time, propulsion force, and velocity information thus producing realistic results.
Multi-objective evolutionary optimization of subsonic airfoils by meta-modelling and evolution control
Authors: D'Angelo S , Minisci E
Published: October 2007

The current work concerns the application of multi-objective evolutionary optimization by approximation function to aerodynamic design. A new general technique, named evolution control (EC), is used in order to manage the on-line enriching of correct solutions database, which is the basis of the learning procedure for the approximators. Substantially, this approach provides that the database, initially quite small and enabling a very inaccurate approximation, should be integrated during the optimization. Such integration is done by means of some choice criteria, allowing deciding which individuals of the current population should be verified. The technique showed being efficacious and very efficient for the considered problem, whose dimensionality are 5. Even if general principle of EC is valid independently from the kind of adopted approximator, this last strongly affects the application. Obtained results are utilized to show how the adoption of artificial neural networks and kriging can differently influence the whole optimization process. Moreover, first results, achieved after reformulating the same problem with seven parameters, support the idea of the performance of the method scale well with dimensionality.
Unsteady numerical simulation in a centrifugal compressor using the time-inclined operator
Authors: Zhou L , Xi G , Cai Y H
Published: October 2007

A unique problem arising from the simulation of rotor-stator interactions is how to treat the unequal numbers of blades in rotor and stator. In the current paper, a numerical method for the calculation of unsteady stator/rotor interaction in turbomachinery stage of arbitrary pitch ratio using time-inclined operator is presented. It is developed on the basis of the program solving the three-dimensional, viscous, steady flow field in a centrifugal compressor. Dual timestepping is adopted to realize the unsteady simulation; time-inclined operator is employed to transform the Navier-Stokes equations. It is realized without an approximation to a ratio of small integers or to scale geometry, the passages used for computation are minimum, and the computational time is also less than others. The viscous terms that neglected in other methods are classified in the source terms, thus, the effects of the viscous terms are never ignored in the case of transforming the Navier-Stokes equations using time-inclined operator. The results using time-inclined operator are also compared with the computation using NUMECA, it shows the program developed by the author can predict the flow field in the centrifugal compressor accurately.
Attitude manoeuvre and vibration control of flexible spacecraft using computed feed-forward input commands and proportional-derivative feedback
Authors: Hu Q
Published: October 2007

The current paper presents an investigation into development of feed-forward and feedback control strategies for active vibration and attitude control of a flexible spacecraft. In this approach, the feed-forward loop consists of a computed-torque scheme and a command shaping technique based on component synthesis vibration suppression (CSVS) method for shaping the input signal. For relaxing the requirement of dynamic linearity in traditional CSVS, a new approach is developed for designing the input component command by utilizing a structure, in which the modal forces of flexible modes vibration are shaped according to a predefined trajectory, to achieve the vibration suppression for the non-linear attitude dynamics. In addition, to follow the predefined trajectory identically or at least as closely as possible, a model-independent feedback control loop is employed, which can accomplish further reduction of the residual vibration of flexible appendages. This proposed control strategy is practical as it does not require direct measurement of mode vibration, and also has a simple structure with low online computational load. Numerical simulations demonstrate the effectiveness of the control strategy.
Deployable membrane structure based on the Bennett linkage
Authors: Yu Y , Luo Y , Li L
Published: October 2007

Deplayable structures based on the alternative forms of the Bennett linkage have been proposed and investigated by some researchers, which can be fully folded to a bundle and deployed to a flat surface. For aerospace applications, a deployable membrane structure based on the alternative form of the Bennett linkage is proposed and developed in the current paper. When fully deployed, four bars of the structure are not coplanar and the membrane tensioned by them can form a hyperboloidal surface. The compatibility between the structure and the membrane during the process of deployment is investigated, and preferred ranges of main design parameters are proposed to ensure the compatibility. The method to construct the assembly of the structure is also considered. In addition, three physical models were manufactured to verify the analytical investigations of the current paper.
Flight dynamics helicopter model validation based on flight test data
Authors: Hiliuta A , Botez R M
Published: October 2007

In the current paper, a new technique for a helicopter model estimation based on flight test data is presented. The state space helicopter models, for different flight conditions, are computed. The method is automatic and is applied when one knows the motion parameters types x, y, and u of a real helicopter and in the absence of any seed matrices. The method is highly convergent, and very good results are obtained for all flight cases. In the introductory part, a bibliographic research is carried on, and the necessary data collection is presented. In the next step, the preliminary estimation of seed matrices, for state-space representation is performed using a non-linear model and small perturbation theory. The last paragraph deals with the seed optimization with respect to different flight conditions. In the end, the model validation and the conclusion on possibilities to further develop and use the present methodology is investigated.
Investigation on the flight characteristics of a conceptual fluidic thrust-vectored aerial tail-sitter
Authors: Saghafi F , Banazadeh A
Published: October 2007

The feasibility of integrating co-flow fluidic thrust-vectoring idea into the dynamics of a small flapless aerial tail-sitter is investigated in this article. The aircraft trimmability in different phases of flight and stability in take-off and level flight, are the main issues of concern for the study presented herein. In this respect, the vehicle's characteristic equations are derived by linearization of the general non-linear equations of motion. Since the vehicle was supposed to be merely controlled by fluidic thrust-vectoring, the concept was novel and some new derivatives are introduced. Margins of the required thrust-vector angle, to obtain a steady-state flight condition, are provided by use of the trim analysis. In addition, stability in take-off transition and level flight is considered utilizing the values of the system poles. Non-linear simulation is developed to examine the aircraft responses to the command inputs and to generate the aircraft trajectory. It is found that the integrated fluidic thrust-vectoring system can be employed as a viable means to achieve both conventional and transition flight for the proposed vehicle. The obtained mathematical model reveals the dependence of the aircraft performance and design criteria on the presented method. This model will be used for further studies on the general aspects of flight dynamics and control systems design for such vehicle.
Experimental observations of an 8 m/s drop test of a metallic helicopter underfloor structure onto a hard surface: Part 1
Authors: Hughes K , Vignjevic R , Campbell J
Published: October 2007

This is the first part of a two-part paper that describes the experimental observations for two similar sections of floor that were dropped onto both hard and water surfaces at 8 m/s, as a part of one experimental campaign. The current paper provides an assessment of a simple box-beam underfloor structure typically found in metallic helicopters and provides an overview of the failure modes and the collapse mechanism observed when dropped onto a hard surface. All findings are supported by quantitative measurements and extensive photographic evidence.

The current paper identifies two limitations with the existing design, which are based upon the observations of the failure modes for different frame types and the performance of the intersection joints. In order to increase the level of crashworthiness currently offered, significant frame and joint redesign is required in order to provide a more progressive collapse. The simple buckling modes currently observed should be avoided, as the existing stroke is not fully utilized in the event of a crash, resulting in an inefficient structure. The current paper also discusses the sensitivity to impact angle, as slight variations from a normal impact may result in a detrimental response.
Identification of structural surfaces' positions on an F/A-18 using the subspace identification method from flight flutter tests
Authors: Beaulieu M N , De Jesus Mota S , Botez R M
Published: October 2007

In the current paper, a linear state-space mathematical model, identified from flight flutter tests is presented, to simulate the aeroelastic deflections of specific structural parts of the NASA F/A-18 Active Aeroelastic Wing research aircraft. The flight flutter tests were performed in steady-level flight with Schroeder frequency excitation induced on the aircraft ailerons by an on-board excitation system activated by the pilot. The results of the flight flutter tests were used to generate an aeroelastic model in which the deflections of the specific aircraft surfaces are functions of the control inputs combined with the deflections of other aircraft surfaces. The F/A-18 linear model is conceived as nine third-order multiple input-single output (MISO) models. Each model has nine inputs and one output. The nine inputs are the differential ailerons deflection and the deflections of all the other parts of the aircraft. The output of each model is the structural deflection of a given aircraft structure. The model's parameters are estimated with the subspace system identification algorithm, an efficient non-iterative algorithm that computes the system matrices directly from the input and output data. The model's quality is evaluated by calculating the fit and correlation coefficients between the model's outputs and the outputs from flight flutter test data. Although the fit coefficient results are very good - between 89 and 99 per cent - the correlation coefficient method gave the best results (nearly 100 per cent). Finally, resampled inputs were used to validate the F/A-18 model's robustness. The model's aircraft structure was validated for flutter flight tests at different Mach numbers and altitudes. The estimated linear model fits the flight flutter test data very well. The subspace method is therefore very convernvenient for model identification from flight flutter tests.
Frequency domain, pseudo-sliding mode control system for a flexible aircraft
Authors: Hess R A , Gama G
Published: October 2007

A control system synthesis technique referred to as pseudo-sliding mode design is applied to the synthesis of a longitudinal flight control system for a flexible aircraft model. The design is interpreted in the frequency domain. As reported in the literature, previous applications of the technique to aircraft flight control have indicated that significant robustness properties in the presence of modelled vehicle damage can be obtained while eliminating the need for control reconfiguration. Although control activity has been shown to be the price to be paid for this robustness, the current application indicates that the pseudo-sliding mode approach is applicable to flexible vehicles. A computer simulation of the flight control system including a mathematical model of the human pilot indicates stable operation in the presence of modelling errors, time delays, sensor noise, turbulence, and modelled vehicle damage.