bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial nar-GFP cell sensors reveal oxygen limitations in highly agitated and aerated laboratory-scale fermentors
Authors: Garcia Jose R , Cha Hyung J , Rao Govind , Marten Mark R , Bentley William E 
Published: January 2009

Abstract

Background
Small-scale microbial fermentations are often assumed to be homogeneous, and oxygen limitation due to inadequate micromixing is often overlooked as a potential problem. To assess the relative degree of micromixing, and hence propensity for oxygen limitation, a new cellular oxygen sensor has been developed. The oxygen responsive E. coli nitrate reductase (nar) promoter was used to construct an oxygen reporter plasmid (pNar-GFPuv) which allows cell-based reporting of oxygen limitation. Because there are greater than 109 cells in a fermentor, one can outfit a vessel with more than 109 sensors. Our concept was tested in high density, lab-scale (5 L), fed-batch, E. coli fermentations operated with varied mixing efficiency – one verses four impellers.

Results
In both cases, bioreactors were maintained identically at greater than 80% dissolved oxygen (DO) during batch phase and at approximately 20% DO during fed-batch phase. Trends for glucose consumption, biomass and DO showed nearly identical behavior. However, fermentations with only one impeller showed significantly higher GFPuv expression than those with four, indicating a higher degree of fluid segregation sufficient for cellular oxygen deprivation. As the characteristic time for GFPuv expression (approx 90 min.) is much larger than that for mixing (approx 10 s), increased specific fluorescence represents an averaged effect of oxygen limitation over time and by natural extension, over space.

Conclusion
Thus, the pNar-GFPuv plasmid enabled bioreactor-wide oxygen sensing in that bacterial cells served as individual recirculating sensors integrating their responses over space and time. We envision cell-based oxygen sensors may find utility in a wide variety of bioprocessing applications.
Assessing drug distribution in tissues expressing P-glycoprotein through physiologically based pharmacokinetic modeling: model structure and parameters determination
Authors: Fenneteau Frédérique , Turgeon Jacques , Couture Lucie , Michaud Véronique , LI Jun , Nekka Fahima 
Published: January 2009

AbstractBackgroundThe expression and activity of P-glycoproteins due to genetic or environmental factors may have a significant impact on drug disposition, drug effectiveness or drug toxicity. Hence, characterization of drug disposition over a wide range of conditions of these membrane transporters activities is required to better characterize drug pharmacokinetics and pharmacodynamics. This work aims to improve our understanding of the impact of P-gp activity modulation on tissue distribution of P-gp substrate.MethodsA PBPK model was developed in order to examine activity and expression of P-gp transporters in mouse brain and heart. Drug distribution in these tissues was first represented by a well-stirred (WS) model and then refined by a mechanistic transport-based (MTB) model that includes P-gp mediated transport of the drug. To estimate transport-related parameters, we developed an original three-step procedure that allowed extrapolation ofin vitromeasurements of drug permeability to thein vivosituation. The model simulations were compared to a limited set of data in order to assess the model ability to reproduce the important information of drug distributions in the considered tissues.ResultsThis PBPK model brings insights into the mechanism of drug distribution in non eliminating tissues expressing P-gp. The MTB model accounts for the main transport mechanisms involved in drug distribution in heart and brain. It points out to the protective role of P-gp at the blood-brain barrier and represents thus a noticeable improvement over the WS model.ConclusionBeing built prior toin vivodata, this approach brings an interesting alternative to fitting procedures, and could be adapted to different drugs and transporters.The physiological based model is novel and unique and brought effective information on drug transporters.
Are animal models predictive for humans?
Authors: Shanks Niall , Greek Ray , Greek Jean 
Published: January 2009

Abstract
It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics.
CHSMiner: a GUI tool to identify chromosomal homologous segments
Authors: Wang Zhen , Ding Guohui , Yu Zhonghao , Liu Lei , Li Yixue 
Published: January 2009

Abstract

Background
The identification of chromosomal homologous segments (CHS) within and between genomes is essential for comparative genomics. Various processes including insertion/deletion and inversion could cause the degeneration of CHSs.

Results
Here we present a Java software CHSMiner that detects CHSs based on shared gene content alone. It implements fast greedy search algorithm and rigorous statistical validation, and its friendly graphical interface allows interactive visualization of the results. We tested the software on both simulated and biological realistic data and compared its performance with similar existing software and data source.

Conclusion
CHSMiner is characterized by its integrated workflow, fast speed and convenient usage. It will be useful for both experimentalists and bioinformaticians interested in the structure and evolution of genomes.
Understanding the nature and mechanism of foot pain
Authors: Hawke Fiona , Burns Joshua 
Published: January 2009

AbstractApproximately one‐quarter of the population are affected by foot pain at any given time. It is often disabling and can impair mood, behaviour, self‐care ability and overall quality of life. Currently, the nature and mechanism underlying many types of foot pain is not clearly understood. Here we comprehensively review the literature on foot pain, with specific reference to its definition, prevalence, aetiology and predictors, classification, measurement and impact. We also discuss the complexities of foot pain as a sensory, emotional and psychosocial experience in the context of clinical practice, therapeutic trials and the placebo effect. A deeper understanding of foot pain is needed to identify causal pathways, classify diagnoses, quantify severity, evaluate long term implications and better target clinical intervention.
A circuit supporting concentration-invariant odor perception in Drosophila
Authors: Asahina Kenta , Louis Matthieu , Piccinotti Silvia , Vosshall Leslie B 
Published: January 2009

Abstract
Background
Most odors are perceived to have the same quality over a large concentration range, but the neural mechanisms that permit concentration-invariant olfactory perception are unknown. In larvae of the vinegar fly Drosophila melanogaster, odors are sensed by an array of 25 odorant receptors expressed in 21 olfactory sensory neurons (OSNs). We investigated how subsets of larval OSNs with overlapping but distinct response properties cooperate to mediate perception of a given odorant across a range of concentrations.

Results
Using calcium imaging, we found that ethyl butyrate, an ester perceived by humans as fruity, activated three OSNs with response thresholds that varied across three orders of magnitude. Whereas wild-type larvae were strongly attracted by this odor across a 500-fold range of concentration, individuals with only a single functional OSN showed attraction across a narrower concentration range corresponding to the sensitivity of each ethyl butyrate-tuned OSN. To clarify how the information carried by different OSNs is integrated by the olfactory system, we characterized the response properties of local inhibitory interneurons and projection neurons in the antennal lobe. Local interneurons only responded to high ethyl butyrate concentrations upon summed activation of at least two OSNs. Projection neurons showed a reduced response to odors when summed input from two OSNs impinged on the circuit compared to when there was only a single functional OSN.

Conclusions
Our results show that increasing odor concentrations induce progressive activation of concentration-tuned olfactory sensory neurons and concomitant recruitment of inhibitory local interneurons. We propose that the interplay of combinatorial OSN input and local interneuron activation allows animals to remain sensitive to odors across a large range of stimulus intensities.
Steroid Profiles in Ovarian Follicular Fluid from Regularly Menstruating Women and Women after Ovarian Stimulation
Authors: Kushnir Mark M , Naessen Tord , Kirilovas Dmitrijus , Chaika Andrey , Nosenko Jelena , Mogilevkina Iryna , Rockwood Alan L , Carlström Kjell , Bergquist Jonas 
Published: January 2009

Abstract
Background: Information on the concentrations of steroids in ovarian follicular fluid (FF) from regularly menstruating (RM) women has been limited because of the absence of methods for the simultaneous quantification of multiple steroids in small volumes of FF. We studied steroid profiles in FF during the early follicular phase of the menstrual cycle and after ovarian stimulation for in vitro fertilization (IVF), and compared concentrations with published values obtained by immunoassay (IA).
Methods: We used liquid chromatography–tandem mass spectrometry (LC-MS/MS) to measure 13 steroids in 40-μL aliquots of FF samples from 21 RM women and from 5 women after ovarian stimulation for IVF. Relationships between concentrations of steroids and their ratios (representations of the enzyme activities) were evaluated within and between subgroups.
Results: The concentrations of testosterone (Te), androstenedione (A4), and estradiol (E2) measured by LC-MS/MS were lower than those previously reported in studies with IAs. In RM women, androgens were the most abundant class of steroids, with A4 being the major constituent. The concentrations of 17-hydroxyprogesterone (17OHP), total androgens, and estrogens were 200- to 1000-fold greater in FF than in serum. Compared with RM women, FF samples from women undergoing ovarian stimulation had significantly higher concentrations of E2 (P = 0.021), pregnenolone (P = 0.0022), 17OHP (P = 0.0007), and cortisol (F) (P = 0.0016), and significantly higher ratios of F to cortisone (P = 0.0006), E2 to estrone (P = 0.0008), and E2 to Te (P = 0.0013).
Conclusions: The data provide the first MS-based concentration values for 13 steroids in ovarian FF from RM women, from estrogen- and androgen-dominant follicles, and from women after ovarian stimulation for IVF.
Specific Determination of β-Galactocerebrosidase Activity via Competitive Inhibition of β-Galactosidase
Authors: Martino Sabata , Tiribuzi Roberto , Tortori Andrea , Conti Daniele , Visigalli Ilaria , Lattanzi Annalisa , Biffi Alessandra , Gritti Angela , Orlacchio Aldo 
Published: January 2009

Abstract
Background: The determination of cellular β-galactocerebrosidase activity is an established procedure to diagnose Krabbe disease and monitor the efficacy of gene/stem cell-based therapeutic approaches aimed at restoring defective enzymatic activity in patients or disease models. Current biochemical assays for β-galactocerebrosidase show high specificity but generally require large protein amounts from scanty sources such as hematopoietic or neural stem cells. We developed a novel assay based on the hypothesis that specific measurements of β-galactocerebrosidase activity can be performed following complete inhibition of β-galactosidase activity.
Methods: We performed the assay using 2–7.5 μg of sample proteins with the artificial fluorogenic substrate 4-methylumbelliferone-β-galactopyranoside (1.5 mmol/L) resuspended in 0.1/0.2 mol/L citrate/phosphate buffer, pH 4.0, and AgNO3. Reactions were incubated for 30 min at 37 °C. Fluorescence of liberated 4-methylumbelliferone was measured on a spectrofluorometer (λex 360 nm, λem 446 nm).
Results: AgNO3 was a competitive inhibitor of β-galactosidase [inhibition constant (Ki) = 0.12 μmol/L] and completely inhibited β-galactosidase activity when used at a concentration of 11 μmol/L. Under this condition, the β-galactocerebrosidase activity was preserved and could be specifically and accurately measured. The assay can detect β-galactocerebrosidase activity in as little as 2 μg cell protein extract or 7.5 μg tissue. Assay validation was performed using (a) brain tissues from wild-type and twitcher mice and (b) murine GALC−/− hematopoietic stem cells and neural precursor cells transduced by GALC-lentiviral vectors.
Conclusions: The procedure is straightforward, rapid, and reproducible. Within a clinical context, our method unequivocally discriminated cells from healthy subjects and Krabbe patients and is therefore suitable for diagnostic applications.
Heightening Levels of Activity and J. S. Bach's Parallel-Section Constructions
Authors: Lester Joel 
Published: January 2009

Abstract
Three constructive principles underlie the large-scale thematic and organizational aspects of J. S. Bach's compositions: (1) the opening of a piece states a core of material that is worked with throughout the composition; (2) recurrences of material almost invariably exhibit a heightening level of activity in some or all musical elements; and (3) movements quite frequently subdivide into roughly parallel sections within which these heightened recurrences appear. The interaction of these three principles, all pertinent to contemporaneous theoretical perspectives, provides a unified perspective on Bach's creations in all genres. This essay explores interactions of the latter principles with the more familiar first one.
An Exotic Enemy: Anti-Japanese Musical Propaganda in World War II Hollywood
Authors: Sheppard W. Anthony 
Published: January 2009

Abstract
The cinema was the most effective medium for anti-Japanese propaganda in the United States during World War II and was the site of music's most important wartime role. From shortly after Pearl Harbor to the end of the U.S. occupation of Japan in 1952, Hollywood produced a large number of films offering negative depictions of the Japanese. Music assumed multiple roles in these anti-Japanese feature films and U.S. government documentaries. Never had Orientalist and racial politics been more clearly evident in music heard by so many as in these productions. These films marshaled preexistent European music, stereotypical Orientalist signs, and traditional Japanese music against the exotic enemy. This essay analyzes some sophisticated examples of musical propaganda that offer new perspectives for the study of cross-cultural musical encounters. For many in the United States, Hollywood film music continues to shape their impressions of Japan and their perceptions of Japanese music.
Schoenberg, Boulez, and Twelve-Tone Composition as “Ideal Type”
Authors: Ashby Arved 
Published: January 2009

Abstract
Twelve-tone music is often defined empirically, in generalized terms of compositional practice. I contend that historians and theorists have neglected a heuristic perspective of twelve-tone composition. One heuristic model proves particularly helpful: the “ideal type,” first described by social scientist Max Weber in “Objectivity' in Social Science and Social Policy” (1904). Weber's ideal type can help to move the discussion away from scientistic ideas of problem solving and overly abstract invocations of “the twelve-tone idea,” and toward what Weber would call the “cultural significance” of twelve-tone methodologies (a move in line with influential revisions to the historiography of scientific “problem solving” proposed by Thomas Kuhn and Imre Lakatos).
Differences of perspective between Arnold Schoenberg and the young Pierre Boulez, at about the time the latter first arrived at Darmstadt, highlight the difficulty in establishing a coherent history of twelve-tone compositional practice (as opposed to a heuristic “ideal type”). The anonymous typescript “Komposition mit zwöölf Töönen,” linked with Schoenberg's Viennese circle of the early 1920s, reveals how the early twelve-tone “discovery” described by Schoenberg is, no less than the later descriptions by Boulez, an a posteriori construct—or, as Kuhn and Lakatos might say, an ideological colonization of past practice.
“Imitar col canto chi parla”: Monteverdi and the Creation of a Language for Musical Theater
Authors: Calcagno Mauro 
Published: January 2009

Abstract
Conventional views of text/music relationships in early Italian opera focus on the imitation of affections. But by dealing exclusively with the referential meanings of texts (e.g., emotions, images, and concepts) these views overlook an important aspect of music's interaction with language. In opera, music also imitates language's contextual and communicative functions—i.e., discourse, as studied today by the subfield of linguistics called pragmatics. In his operas Monteverdi fully realized Peri's ideal of “imitating in song a person speaking” (“imitar col canto chi parla”) by musically emphasizing those context-dependent meanings that emerge especially in ordinary language and that are prominent in dramatic texts, as opposed to poetry and prose. Such meanings are manifest whenever words such as “I,” “here,” and “now” appear— words called “deictics”—with the function of situating the speaker/singer's utterances in a specific time and place. Monteverdi highlights deictics through melodic and rhythmic emphases, repetition, shifts of meter, style, and harmony, as part of a strategy to create a musical language suited to opera as a genre and to singers as actors. In Il ritorno d'Ulisse in patria and L'incoronazione di Poppea, this strategy serves large-scale dramaturgical aims with respect to the relationships among space, time, and character identity, highlighting issues also discussed within the contemporary intellectual context.
Stravinsky's Music in Hitler's Germany
Authors: Evans Joan 
Published: January 2009

Abstract
This investigation of the reception in Nazi Germany of the work (and person) of Igor Stravinsky offers new insights into the issue of modern music in Hitler's Germany. As the most prominent modernist composer of the period, Stravinsky was the chief beneficiary of Germany's desire, after the xenophobic early Nazi years, to rejoin the European cultural community. Thanks to the determination of his supporters, and aided by the greater accessibility of his 1930s works, Stravinsky's music achieved a significant position in the musical life of the New Germany, which it maintained until the outbreak of war. Modern-minded critics articulated the ideological basis for his “rehabilitation”: although rooted in a foreign musical tradition, Stravinsky was an “Aryan” composer with acceptable political views, whose tonally based music revealed suitably “national” qualities.
Many foreign composers, including the antifascist Béla Bartók, shared Stravinsky's desire for German performances. Whether they allowed this to temper their modernist tendencies is difficult to determine. What is certain is that their tonally based music allowed many (racially and politically acceptable) foreign composers to find an audience in Nazi Germany. It also made feasible Germany's desire to reconnect with the larger musical world.
Britten's Dubious Trysts
Authors: Whitesell Lloyd 
Published: January 2009

Abstract
One hypothesis pursued in contemporary queer musicology argues that music provides an arena for reflection on a composer's experience of a marginal sexual identity. The music of Benjamin Britten has furnished material for a recent outpouring of such criticism. Much of this work, however, addresses covert meanings constrained by censorship and directed toward a minority audience of initiates or sympathizers; its impact on Britten reception in general remains unclear. I propose that Britten's music dramatizes a deviant perspective in fundamental ways, resulting in a queer aesthetic whose import extends to all listeners. Britten composes dramas of psychological reorientation from the following elements: the appearance of a stranger, a figure of worldly or spiritual initiation, in opposition to the familiar protagonist; and the setting in a limbo between worlds, making possible uncanny meetings whose vocal exchanges convey erotic knowledge. The confrontation of different perspectives casts the protagonist into disorientation and leads to bonds of identification across incompatible positions. Through the protagonist's perspective, such effects of deviant perception and cross-identification extend to the audience. Britten's queer aesthetic is not so much defiant or antagonistic as Socratic—based on a logic of persuasion and transformative dialogue.
Exploring the Generality of Recruitment Hypotheses for Largemouth Bass along a Latitudinal Gradient of Florida Lakes
Authors: Rogers Mark W. , Allen Micheal S. 
Published: January 2009

AbstractLatitudinal influences on growing season length and winter severity cause variation in prerecruitment life history across species distributions. We evaluated two recruitment hypotheses for a broadly distributed species, largemouth bass Micropterus salmoides, at the southern extent of their natural range. We tested (1) whether early hatching provided a growth and survival advantage relative to later hatching through their first summer and (2) whether overwinter size‐selective mortality strongly influenced recruitment to age 1 across Florida's latitudinal gradient. We sampled the 2003 and 2004 year‐classes at six Florida lakes that spanned latitudes from 27°0′N to 30°5′N. Our results did not fully conform to our hypotheses or the results frequently reported from more northerly latitudes because largemouth bass that hatched early did not exhibit a growth and survival advantage at all lakes and we did not detect strong size‐selective overwinter mortality. Early hatching at south Florida lakes resulted in slow growth for three of four lake and year combinations and early‐hatched fish never exhibited a survival advantage relative to later‐hatched fish, which was probably due to cool water temperatures soon after hatching. Environmental variability influenced the interactions between hatching period, growth, and survival for Florida's largemouth bass populations, which has implications for understanding fish recruitment across broad spatial scales.