bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment With Autologous Antigen-Presenting Cells Activated With the HER-2 –Based Antigen Lapuleucel-T: Results of a Phase I Study in Immunologic and Clinical Activity in HER-2–Overexpressing Breast Cancer
Authors: Park John W. , Melisko Michelle E. , Esserman Laura J. , Jones Lori A. , Wollan Jami Breen , Sims Robert 
Published: August 2007

PurposeLapuleucel-T (APC8024), an autologous active cellular immunotherapy, was prepared from peripheral-blood mononuclear cells, including antigen-presenting cells, that were activated in vitro with recombinant fusion protein BA7072. This antigen construct consisted of sequences from intracellular and extracellular domains of human epidermal growth factor receptor 2 (HER-2) linked to granulocyte-macrophage colony-stimulating factor. We conducted a phase I study to evaluate the safety and immunologic activity of lapuleucel-T in patients with HER-2–overexpressing metastatic breast cancer.Patients and MethodsMetastatic breast cancer patients whose tumors overexpressed or amplified HER-2 were eligible. Patients underwent leukapheresis and subsequent lapuleucel-T infusion 2 days later at weeks 0, 2, and 4. Patients who achieved a partial response (PR) or had stable disease (SD) lasting through week 48 were eligible for re-treatment using the same protocol and dose as their initial treatment. End points included safety, immunologic activity, and antitumor activity.ResultsNineteen patients were enrolled; 18 patients received treatment. Therapy was well tolerated, with no grade 3 or 4 adverse events associated with the treatment. Significant cellular immune responses specific for the immunizing antigen and HER-2 sequences were induced after treatment, as measured by lymphocyte proliferation and interferon gamma enzyme-linked immunospot assay. One patient experienced a PR lasting 6 months. Three additional patients had SD lasting more than 1 year.ConclusionAutologous active cellular immunotherapy with lapuleucel-T was feasible, safe, and well tolerated. The treatment stimulated significant immune responses, which were enhanced after boost infusions. Lapuleucel-T therapy was associated with tumor response or extended disease stabilization in some patients and warrants further investigation.
Absence of eye shine and tapetum in the heterogeneous eye ofAnthocharisbutterflies (Pieridae)
Authors: Takemura Shin-ya , Stavenga Doekele G. , Arikawa Kentaro 
Published: August 2007

SUMMARYInsect eyes are composed of spectrally heterogeneous ommatidia, typically with three different types. The ommatidial heterogeneity in butterflies can be identified non-invasively by the colorful eye shine, the reflection from the tapetal mirror located at the proximal end of the ommatidia, which can be observed by epi-illumination microscopy. Since the color of eye shine is determined by the spectral properties of the ommatidia, it has been tentatively related to color vision. In the course of a survey of ommatidial heterogeneity in butterflies, we found that members of the pierid genus Anthocharis lack the eye shine. We therefore carried out anatomy of the eye of the yellow tip, Anthocharis scolymus, and correlated it with the absence of the tapetum. The butterfly tapetum is a remnant of the ancestral moth tapetum, a trait that has been completely lost in the papilionids and also, as now appears, in the genus Anthocharis. Anatomical investigations also revealed that, considering rhabdom shape,peri-rhabdomal pigment clusters and autofluorescence, the ommatidia can be divided in at least two different types, which are randomly distributed in the retina.
Kinematic analysis of an appetitive food-handling behavior: the functional morphology of Syrian hamster cheek pouches
Authors: Buckley Carolyn A. , Schneider Jill E. , Cundall David 
Published: August 2007

SUMMARY
Prodigious food hoarding in Syrian hamsters Mesocricetus auratusWaterhouse is strongly linked to appetite and is made possible by large internal cheek pouches. We provide a functional analysis of the cheek pouch and its associated retractor muscle. Frame-by-frame analysis of videotaped pouch-filling behavior revealed multiple jaw cycles for each food item pouched and the use of more jaw cycles to pouch large food items (∼2.5 g chow pellets) than small (corn kernels or sunflower seed with husks). These results stand in contrast to previously reported pouching kinematics in the externally pouched Dipodomys deserti, which uses only one jaw cycle per pouching event. Comparison of pouching and mastication in the same individuals also suggests that in Syrian hamsters, feeding jaw cycles are modulated to accommodate pouch filling primarily by the addition of a pause between fast open and fast close phases, which we call `gape phase'. Contrary to previous assertions, the retractor muscle does not merely provide structural support for the full pouch during locomotion. Video analysis of ten hamsters with unilaterally denervated retractor muscles and electrophysiological study of an anaesthetized subject confirmed that retractor muscle activity during pouch filling increases pouching efficiency for food items subsequent to the first.
Functional identification of an osmotic response element (ORE) in the promoter region of the killifish deiodinase 2 gene (FhDio2)
Authors: López-Bojórquez L. , Villalobos P. , García-G. C. , Orozco A. , Valverde-R. C. 
Published: August 2007

SUMMARY
The physiological role played by thyroid hormones (TH) in hydro-osmotic homeostasis in fish remains a controversial issue. Previous studies have shown that in Fundulus heteroclitus (killifish) hypo-osmotic stress increases liver iodothyronine deiodinase type 2 (D2) mRNA and D2 activity. In this study we identified two conserved osmotic response element (ORE) motifs in the promoter region of the killifish D2 gene (FhDio2) and examined their possible role in the transcriptional regulation of FhDio2during hypo-osmotic stress. As assessed by the electrophoretic mobility shift assay, results from in vivo and in vitro experiments demonstrate that exposure to an abrupt hyposmotic challenge triggers in the liver of killifish a strong nuclear recruitment of a putative osmotic response element binding protein (OREBP). This protein–DNA binding is time-dependent, attains a maximum within 2–8 h after the osmotic stress,and is followed by a significant increase in D2 activity. Furthermore,protein–DNA binding and the subsequent elevation in enzyme activity were blocked by the tyrosine kinase inhibitor genistein. Thus, during hypo-osmotic stress, a putative OREBP kinase-activated pathway stimulates FhDio2transcription and enzymatic activity. These data and the fact that D2 is the major enzyme providing local intracellular T3 suggest that TH plays a direct role in osmoregulation in fish, possibly by participating in hepatic ammonia metabolism. This study provides important insight into the physiological role of TH in hydro-osmotic homeostasis in fish.
The hungry caterpillar: an analysis of how carbohydrates stimulate feeding inManduca sexta
Authors: Glendinning John I. , Jerud Adrienne , Reinherz Ariella T. 
Published: August 2007

SUMMARYIn most insects, the taste of carbohydrates stimulates an immediate appetitive response. The caterpillar of Manduca sexta is an exception to this general pattern. Despite eliciting a strong peripheral gustatory response, high concentrations of carbohydrates (e.g. glucose or inositol)stimulate the same intensity of biting as water during 2-min tests. We suspected that the lack of feeding stimulation reflected the fact that prior studies used single carbohydrates (e.g. sucrose), which M. sextawould rarely encounter in its host plants. We hypothesized that the feeding control system of M. sexta responds selectively to carbohydrate mixtures. To test this hypothesis, we ran three experiments. First, we stimulated the two taste sensilla that respond to carbohydrates (the lateral and medial styloconic) with a battery of carbohydrates. These sensilla responded exclusively to sucrose, glucose and inositol. Second, we determined the response properties of the carbohydrate-sensitive taste cells within both sensilla. We found that one class of carbohydrate-sensitive taste cell responded to sucrose, and two other classes each responded to glucose and inositol. Third, we examined the initial biting responses of caterpillars to disks treated with solutions containing single carbohydrates (sucrose, glucose or inositol) or binary mixtures of these carbohydrates. The only solutions that stimulated sustained biting were those that activated all three classes of taste cell (i.e. sucrose+inositol or sucrose+glucose). We propose that the brain of M. sexta monitors input from the different classes of carbohydrate-sensitive taste cell, and generates protracted feeding responses only when all three classes are activated.
Unsteady locomotion: integrating muscle function with whole body dynamics and neuromuscular control
Authors: Biewener Andrew A. , Daley Monica A. 
Published: August 2007

SUMMARY
By integrating studies of muscle function with analysis of whole body and limb dynamics, broader appreciation of neuromuscular function can be achieved. Ultimately, such studies need to address non-steady locomotor behaviors relevant to animals in their natural environments. When animals move slowly they likely rely on voluntary coordination of movement involving higher brain centers. However, when moving fast, their movements depend more strongly on responses controlled at more local levels. Our focus here is on control of fast-running locomotion. A key observation emerging from studies of steady level locomotion is that simple spring-mass dynamics, which help to economize energy expenditure, also apply to stabilization of unsteady running. Spring-mass dynamics apply to conditions that involve lateral impulsive perturbations, sudden changes in terrain height, and sudden changes in substrate stiffness or damping. Experimental investigation of unsteady locomotion is challenging, however, due to the variability inherent in such behaviors. Another emerging principle is that initial conditions associated with postural changes following a perturbation define different context-dependent stabilization responses. Distinct stabilization modes following a perturbation likely result from proximo-distal differences in limb muscle architecture, function and control strategy. Proximal muscles may be less sensitive to sudden perturbations and appear to operate, in such circumstances, under feed-forward control. In contrast, multiarticular distal muscles operate, via their tendons, to distribute energy among limb joints in a manner that also depends on the initial conditions of limb contact with the ground. Intrinsic properties of these distal muscle–tendon elements, in combination with limb and body dynamics, appear to provide rapid initial stabilizing mechanisms that are often consistent with spring-mass dynamics. These intrinsic mechanisms likely help to simplify the neural control task, in addition to compensating for delays inherent to subsequent force- and length-dependent neural feedback. Future work will benefit from integrative biomechanical approaches that employ a combination of modeling and experimental techniques to understand how the elegant interplay of intrinsic muscle properties, body dynamics and neural control allows animals to achieve stability and agility over a variety of conditions.
Analytical and numerical investigation of the flow past the lateral antennular flagellum of the crayfishProcambarus clarkii
Authors: Humphrey Joseph A. C. , Mellon DeForest 
Published: August 2007

SUMMARYAnalytical and numerical methodologies are combined to investigate the flow fields that approach and pass around the lateral flagellum of the crayfish Procambarus clarkii. Two cases are considered, the first being that of a free-flicking flagellum and the second corresponding to a flagellum fixed inside a small bore tube. The first case is the natural one while the second corresponds to the experimental configuration investigated by Mellon and Humphrey in the accompanying paper. In that study the authors observed a hydrodynamic-dependent asymmetry in the spiking responses recorded from single, bimodally sensitive local interneurons (Type I) in the crayfish deutocerebrum, whereby the direction of an abruptly initiated flow of freshwater (or odorant) past the flagellum resulted in consistently larger numbers of spikes in response to the hydrodynamic stimulation when the flow direction was proximal-to-distal. In this communication we show that the proximal-to-distal and the distal-to-proximal flows produced in the flagellum-in-tube experiment correspond closely to the flows associated with the downward and upward flicks, respectively, of a free-flicking flagellum. We also show from calculations of the drag forces acting on the putative mechanoreceptor sensilla circumferentially distributed around a free-flicking flagellum that there are at least three sources of hydrodynamic asymmetry possibly related to the electrophysiological asymmetry observed: (i) the sense of the drag forces acting on medial and lateral mechanoreceptors changes in the same way for both with change in flick direction; (ii) during a downward(an upward) flick, a ventral (dorsal) mechanoreceptor experiences a larger drag force magnitude than a dorsal (ventral) mechanoreceptor; (iii) because of the difference in speeds between downward and upward flicks, the magnitudes of the drag forces acting on medial, lateral and ventral mechanoreceptors during a downward flick are about two times larger relative to the forces acting on medial, lateral and dorsal mechanoreceptors during an upward flick. All three of these naturally occurring hydrodynamic asymmetries are correctly reproduced in the flagellum-in-tube experiment.
Developmental changes in central O2 chemoreflex in Rana catesbeiana: the role of noradrenergic modulation
Authors: Fournier Stéphanie , Allard Mathieu , Roussin Stéphanie , Kinkead Richard 
Published: August 2007

SUMMARY
The in vitro brainstem preparation from Rana catesbeianashows a functional central O2 chemoreflex. Acute brainstem exposure to hypoxic superfusate elicits lung burst frequency responses that change over the course of development. Based on studies suggesting that brainstem noradrenergic neurons are involved in this reflex, we tested the following two hypotheses in vitro: (1) activation of adrenoceptors is necessary for the expression of the fictive lung ventilation response to hypoxia, and (2)changes in fast, Cl–-dependent neurotransmission(GABA/glycine) contribute to developmental changes in noradrenergic modulation. Experiments were performed on preparations from pre-metamorphics tadpoles (TK stages V–XIII) and adult bullfrogs. Acute exposure to hypoxic superfusate (98% N2, 2% CO2) increased fictive lung ventilation frequency in the pre-metamorphic group, whereas a decrease was observed in adults. Buccal burst frequency was unchanged by hypoxia. Noradrenaline (NA; 5 μmol l–1) bath application mimicked both fictive breathing responses and application of theα 1-antagonist prazosine (0.5 μmol l–1)blocked the lung burst response to hypoxia in both groups. Blocking GABAA/glycine receptors with a bicuculine/strychnine mixture (1.25μmol l–1/1.5 μmol l–1, respectively)or activation of GABAB pre-synaptic autoreceptors with baclofen(0.5 μmol l–1) prevented the lung burst response to hypoxia and to the α1-agonist phenylephrine (25 μmol l–1) in both stage groups. We conclude that NA modulation contributes to the central O2 chemoreflex in bullfrog, which acts via GABA/glycine pathways. These data suggest that maturation of GABA/glycine neurotransmission contributes to the developmental changes in this chemoreflex.
Swimming in the upside down catfishSynodontis nigriventris: it matters which way is up
Authors: Blake Robert W. , Chan Keith H. S. 
Published: August 2007

SUMMARYSynodontis nigriventris is a surface-feeding facultative air-breather that swims inverted with its zoological ventral side towards the water surface. Their near-surface drag is about double the deeply submerged drag (due to wave drag) and roughly twice the sum of frictional and pressure drags. For streamlined technical bodies, values of wave drag augmentation near the surface may be five times the deeply submerged values. However, the depth dependence of drag is similar for fish and streamlined technical bodies, with augmentation vanishing at about 3 body diameters below the surface. Drag`inverted' is approximately 15% less than that `dorsal side up' near the surface. Consistent with this, at any given velocity, tailbeat frequency is lower and stride length higher for inverted swimming in surface proximity(P&lt;0.05). Deeply submerged, there are no significant differences in drag and kinematics between postures (P&gt;0.05). At the critical Froude number of 0.45, speeds in surface proximity correspond to prolonged swimming that ends in fatigue. To exceed these speeds, the fish must swim deeply submerged and this behaviour is observed. Inverted swimming facilitates efficient air breathing. Drag dorsal side up during aquatic surface respiration is 1.5 times the value for the inverted posture. Fast-starts are rectilinear, directly away from the stimulus. Average and maximum velocity and acceleration decrease in surface proximity (P&lt;0.05) and are higher inverted (maximum acceleration: 20–30 m s–2; P&lt;0.05) and comparable to locomotor generalists (e.g. trout). Mechanical energy losses due to wave generation are about 20% for inverted and 40% for dorsal side up, and lower than for trout fast-starting in shallow water (70% losses); bottom effects and large amplitude C-starts (c.f. relatively low amplitude rectilinear motions in S. nigriventris)enhance resistance in trout. S. nigriventris probably evolved from a diurnal or crepuscular `Chiloglanis-like' benthic ancestor. Nocturnality and reverse countershading likely co-evolved with the inverted habit. Presumably, the increased energy cost of surface swimming is offset by exploiting the air–water interface for food and/or air breathing.
Assessment of repeated displays: a test of possible mechanisms
Authors: Van Dyk Daniel A. , Taylor Alan J. , Evans Christopher S. 
Published: August 2007

SUMMARYMany animals signal their resource holding potential (RHP) to deter competitors from engaging them in potentially costly fights. Studies of this opponent assessment function have generated important insights into signal design and evolution. In the case of sounds, rate of production is often a salient feature. We used digital video playback to conduct analogous experiments exploring the importance of temporal variation in visual signals. Our study focused on the push-up display of male Jacky dragons Amphibolurus muricatus, an Australian agamid lizard. This stereotyped movement-based signal is commonly performed during male–male contests. A previous study has shown that Jacky dragons responses are influenced by the overall display rate of a video conspecific. We built upon this finding by investigating the effect of short-term variation in display rate. Each playback sequence varied systematically across a different combination of display parameters, while keeping the total number of push-ups constant. Other potential cues, such as morphology and the characteristics of individual motor patterns, were precisely controlled. The aggressive signalling and locomotor behaviour of subject males varied significantly between sequences. Most notably, performance of throat expansions, a typical agamid threat posture,was suppressed by video sequences with temporal clumping of displays. These results show that lizards are sensitive to differences in the temporal fine structure of display sequences and suggest that display concentration is an important assessment cue.
Effects of mass and body composition on fasting fuel utilisation in grey seal pups (Halichoerus grypusFabricius): an experimental study using supplementary feeding
Authors: Bennett Kimberley A. , Speakman John R. , Moss Simon E. W. , Pomeroy Paddy , Fedak Mike A. 
Published: August 2007

SUMMARYThis study used supplementary feeding to test the hypothesis that fuel partitioning during the postweaning fast in grey seal pups is affected by size and composition of energy reserves at weaning, and by extra provisioning. Mass and body composition changes were measured during suckling and fasting to investigate the effect of natural differences in energy reserves at weaning on subsequent allocation of fat and protein to energy use. We fed seven pups for 5 days after weaning, to investigate the effect of increased fuel availability, and particularly protein, on fuel utilisation. After correcting for protein used during the moult, the proportional contribution of fat was 86–99% of total energy use. Pups with greater energy reserves, i.e. those that were heavier and fatter at weaning, had higher rates of fat and energy use. There was no significant relationship between adiposity at weaning and proportional contribution of fat to energy use, perhaps due to a limited sample size or range of body masses and adiposity. Supplemented individuals used energy, specifically fat, much faster and utilised proportionally less of their endogenous protein by departure than non-supplemented individuals. Fat metabolism contributed a similar percentage to daily energy use in both groups. These findings show that pups spare protein, even when energy use is dramatically increased. Pups that receive greater maternal provisioning and lay down more protein may have increased survival chances at sea. This study highlights the importance of protein reserves in first year survival of grey seal pups.
A comprehensive overview of hydrogen engine design features
Authors: Verhelst S , Verstraeten S , Sierens R 
Published: August 2007

Realizing decreased CO2 emissions from the transport sector will be possible in the near future when substituting (part of) the currently used hydrocarbon-fuelled internal combustion engines (ICEs) with hydrogen-fuelled ICEs. Hydrogen-fuelled ICEs have advanced to such a stage that, from the engine point of view, there are no major obstacles to doing this. The present paper indicates the advantages of hydrogen as a fuel for spark ignition (SI) internal combustion engines. It also shows how the hydrogen engine has matured. An extensive overview is given of the literature on experimental studies of abnormal combustion phenomena, mixture formation techniques, and load control strategies for hydrogen-fuelled engines. The Transport Technology research group of the Department of Flow, Heat and Combustion Mechanics at Ghent University has been working on the development and optimization of hydrogen engines for 15 years. An overview of the most important experimental results is presented with special focus on the most recent findings. The article concludes with a list of engine design features of dedicated hydrogen SI engines.