bluuebunny/crossref_metadata_2025 huggingface dataset:
A ROBUST AND FRIENDLY HUMAN–ROBOT INTERFACE SYSTEM BASED ON NATURAL HUMAN GESTURES
Authors: CHANG MING-SHAUNG , CHOU JUNG-HUA
Published: September 2010

In this paper, we design a robust and friendly human–robot interface (HRI) system for our intelligent mobile robot based only on natural human gestures. It consists of a triple-face detection method and a fuzzy logic controller (FLC)-Kalman filter tracking system to check the users and predict their current position in a dynamic and cluttered working environment. In addition, through the combined classifier of the principal component analysis (PCA) and back-propagation artificial neural network (BPANN), single and successive commands defined by facial positions and hand gestures are identified for real-time command recognition after dynamic programming (DP). Therefore, the users can instruct this HRI system to make member recognition or expression recognition corresponding to their gesture commands, respectively based on the linear discriminant analysis (LDA) and BPANN. The experimental results prove that the proposed HRI system perform accurately in real-time face detection and tracking, and robustly react to the corresponding gesture commands at eight frames per second (fps).
Safety enhancements of home lift, position and rehabilitation (HLPR) chair
Authors: Zalewski Janusz , Guo Dahai , Csavina Kristy , Sweeney James , Bostelman Roger , Kirsner Kenneth
Published: September 2010

According to recent studies published in AI Magazine (2005), in 2000, "people aged 65 and older made up 12.3 percent of the U.S. population, while by 2030, they will constitute 19.2 percent, after which growth is projected to level off so that this cohort represents 20 percent of the population in 2050." In response to respective needs, the National Institute of Science and Technology (NIST), Intelligent Systems Division, began the Healthcare Mobility Project to address this healthcare issue of patient lift and mobility, and began developing the Home Lift, Position, & Rehabilitation (HLPR) chair to investigate specific areas of mobility and rehabilitation. The HLPR chair has been built as a prototype but a significant number of unresolved issues exist and are being researched. The objective of this particular project is to investigate the computer and software safety issues in the design, implementation and use of the HLPR chair.
A concept for a medical device plug-and-play architecture based on web services
Authors: Pöhlsen Stephan , Schlichting Stefan , Strähle Markus , Franz Frank , Werner Christian
Published: September 2010

Medical device interoperability is still an issue. Standards exist only for specific areas like HL7 and DICOM, or have not been widely adopted like ISO/IEEE 11073 except for the domain information model at the semantic level. An approach that covers interoperability below the semantics is proposed. It is based on Web services which are widely accepted outside the medical device application domain. In particular the architecture is build on the upcoming Device Profile for Web Services (DPWS). It is a collection of existing Web services specifications for service discovery, interface description, event notification, and security. It is designed for resource-constrained devices and thus seems to be suitable as a basis for medical device plug-and-play.
A publish-subscribe architecture and component-based programming model for medical device interoperability
Authors: King Andrew , Procter Sam , Andresen Dan , Hatcliff John , Warren Steve , Spees William , Jetley Raoul , Jones Paul , Weininger Sandy
Published: September 2010

Medical devices historically have been monolithic units --- developed, validated, and approved by regulatory authorities as standalone entities. Modern medical devices increasingly incorporate connectivity mechanisms that offer the potential to stream device data into electronic health records, integrate information from multiple devices into single customizable displays, and coordinate the actions of groups of cooperating devices to realize "closed loop" scenarios and automate clinical workflows.

In this paper, we describe a publish-subscribe architecture for medical device integration based on the Java Messaging Service. We provide a overview of a model-based development environment that we have built for rapidly programming device coordination scenarios. We assess the extent to which this framework is capable of supporting and complementing the Integrated Clinical Environment that has been proposed by the Medical Device Plug and Play Interoperability Project The implementation of this framework is freely available and open source. One of the primary goals of the framework is to provide researchers in acadaemia, industry, and government with an open test bed for exploring development, quality assurance, and regulatory issues related to medical device interoperability.
What is multithreading and multi-core?
Authors: Kissell Kevin D.
Published: September 2010

Is multithreading better than multi-core? Is multi-core better than multithreading? The fact is that the best vehicle for a given application might have one, the other or both. Or neither. They are independent (but complementary) design decisions. As multithreaded processors and multi-core chips become the norm, architects and designers of digital systems need to understand their respective attributes, advantages and disadvantages. Both multithreading and multi-core approaches exploit the concurrency in a computational workload. The cost, in silicon, energy and complexity, of making a CPU run a single instruction stream ever faster goes up nonlinearly and eventually hits a wall imposed by the physical limitations of circuit technology. That wall keeps moving out a little farther every year, but cost- and power-sensitive designs are constrained to follow the bleeding edge from a safe distance. Fortunately, virtually all computer applications have some degree of concurrency: At least some of the time, two or more independent tasks need to be performed simultaneously. Taking advantage of concurrency to improve computing performance and efficiency isn't always trivial, but it's certainly easier than violating the laws of physics.
Understanding deep web search interfaces
Authors: Khare Ritu , An Yuan , Song Il-Yeol
Published: September 2010

This paper presents a survey on the major approaches to search interface understanding. The Deep Web consists of data that exist on the Web but are inaccessible via text search engines. The traditional way to access these data, i.e., by manually filling-up HTML forms on search interfaces, is not scalable given the growing size of Deep Web. Automatic access to these data requires an automatic understanding of search interfaces. While it is easy for a human to perceive an interface, machine processing of an interface is challenging. During the last decade, several works addressed the automatic interface understanding problem while employing a variety of understanding strategies. This paper presents a survey conducted on the key works. This is the first survey in the field of search interface understanding. Through an exhaustive analysis, we organize the works on a 2-D graph based on the underlying database information extracted and based on the technique employed.
Lisp implementations
Authors: van Roggen Walter
Published: September 2010

The Lisp community has traditionally been fairly diverse and widespread. Many different dialects have been implemented over the years, embodying different philosophies and displaying various strengths and weaknesses. Lately there have been fewer and more standardized Lisps and a more widespread use of Lisp in solving problems on a wider range of machines.
Peopling of the Pacific: A Holistic Anthropological Perspective
Authors: Patrick V. Kirch
Published: September 2010

The human colonization of the Pacific is an enduring problem in historical anthropology. Recent advances in archaeology, historical linguistics, and bioanthropology have coalesced to form a set of models for population movements and interactions in Oceania, which have been tested on independent data sets. Earliest human movements into Near Oceania began about 40,000 years ago, resulting in great cultural, linguistic, and genetic diversity in this region. About 4000 years ago, the expansion of Austronesian speakers out of Southeast Asia led to the emergence of the Lapita cultural complex in Near Oceania. The Lapita expansion into Remote Oceania, commencing about 1200 BC, led ultimately to the settlement of the vast eastern Pacific, ending with the colonization of New Zealand about AD 1250. Polynesians probably reached the coast of South America, returning with the sweet potato and possibly the bottle gourd. Polynesian influences on New World cultures remain a topic of debate.
The Commodification of Language
Authors: Heller Monica
Published: September 2010

Although language can always be analyzed as a commodity, its salience as a resource with exchange value has increased with the growing importance of language in the globalized new economy under the political economic conditions of late capitalism. This review summarizes how and in which ways those conditions have a commodifying effect on language and focuses on contemporary tensions between ideologies and practices of language in the shift from modernity to late modernity. It describes some of these tensions in key sites: tourism, marketing, language teaching, translation, communications (especially call centers), and performance art.
Food and the Senses
Authors: Sutton David E.
Published: September 2010

This review makes the case for anthropological reflection on the intersection of food and the senses. Given that a focus on food and the senses allows us to explore some of the most basic boundaries of inside and outside, private and public, individual and collective, this topic offers an excellent window onto that elusive notion of everyday life that anthropologists wish to understand theoretically and examine ethnographically. At the same time, food is a key component of ritual, which has typically been understood as heightening or stimulating sensory experience to instill social or cosmological values. Food and the senses overlap in notions of taste as distinction and in an increasing recognition of the culturally cultivated phenomenon of synesthesia. Furthermore, in making food and the senses central to understanding wider social issues, this review argues for the productivity of a concept of “gustemology” in opening up new realms of ethnographic and theoretical inquiry.
A Life of Research in Biological Anthropology
Authors: Harrison Geoffrey A.
Published: September 2010

I much appreciated being invited to write a contribution for this journal, but initially presumed that what was required was a comprehensive review of some major issue in biological anthropology. Indeed I drafted a contribution on the history of the subject during the second part of the twentieth century. I was then firmly told that this was not what was wanted, rather something much more autobiographical. Well that is what you have got: an extremely personal account of my own research career over some 50 years in biological anthropology. I have summarized the results of what I consider the main projects I and my colleagues have undertaken and tried to document successes and failures. I cannot claim any earth-shattering discovery but hope that we have contributed in a substantial way to the further understanding of the nature of human variation, a main concern of biological anthropology in the second half of the twentieth century.
Water Sustainability: Anthropological Approaches and Prospects
Authors: Orlove Ben , Caton Steven C.
Published: September 2010

Water has become an urgent theme in anthropology as the worldwide need to provide adequate supplies of clean water to all people becomes more challenging. Anthropologists contribute by seeing water not only as a resource, but also as a substance that connects many realms of social life. They trace the different forms of valuing water, examine the often unequal distribution of water, explore the rules and institutions that govern water use and shape water politics, and study the multiple, often conflicting knowledge systems through which actors understand water. They offer ethnographic insights into key water sites—watersheds, water regimes, and waterscapes—found in all settings, though with widely varying characteristics. Anthropologists provide a critical examination of a concept called integrated water resource management (IWRM), which has become hegemonic in the global discourse of sustainable development.
Miocene Hominids and the Origins of the African Apes and Humans
Authors: Begun David R.
Published: September 2010

In the past 20 years, new discoveries of fossil apes from the Miocene have transformed our ideas about the timing, geography, and causes of the evolution of the African apes and humans. Darwin predicted that the common ancestor of African apes and humans would be found in Africa. Yet the majority of fossil great apes are from Europe and Asia. I briefly review the fossil record of great apes and then examine the main competing hypotheses of our origins, African or European, inspired by these recent discoveries, concluding that elements of both ideas are likely to be correct. Given current interpretations of the paleobiology of fossil apes and relationships among living hominids, I suggest that the last common ancestor of chimpanzees and humans was morphologically unique, but more chimpanzee-like than hominin-like: a knuckle-walker with a chimpanzee-sized brain, canine sexual dimorphism, and many probable behavioral similarities to living chimpanzees.
The Anthropology of Genetically Modified Crops
Authors: Stone Glenn Davis
Published: September 2010

By late in the twentieth century, scientists had succeeded in manipulating organisms at the genetic level, mainly by gene transfer. The major impact of this technology has been seen in the spread of genetically modified (GM) crops, which has occurred with little controversy in some areas and with fierce controversy elsewhere. GM crops raise a very wide range of questions, and I address three areas of particular interest for anthropology and its allied fields. First are the political-economic aspects of GM, which include patenting of life forms and new relationships among agriculture, industry, and the academy. Second is the wide diversity in response and resistance to the technology. Third is the much-debated question of GM crops for the developing world. This analysis is approached first by determining what controls research agendas and then by evaluating actual impacts of crops to date.
The Southwest School of Landscape Archaeology
Authors: Fowles Severin
Published: September 2010

A distinctive school of landscape archaeology is emerging in the American Southwest. The Southwest School, as here defined, has its roots in a unique set of historical relationships among archaeologists, ethnographers, indigenous people, and an intoxicating physical setting that has long provided scholarly inspiration. The most significant contribution of this school, however, is the manner in which it has begun to engage Native American intellectuals, not as data to be studied, but as interlocutors with distinct epistemological stances who have their own contributions to make toward the theorization of cultural landscapes generally. As such, the Southwest School stands poised to offer an important alternative to the more widely read landscape approaches currently popular in British archaeology.
Defining Behavioral Modernity in the Context of Neandertal and Anatomically Modern Human Populations
Authors: Nowell April
Published: September 2010

This review summarizes current thinking about the concept of modern behavior in the context of Neandertals and anatomically modern humans. The decoupling of modern anatomy and modern behavior has prompted researchers to reframe studies of the emergence of modern humans as a debate that explicitly focuses on the origins of behavioral modernity making its intersection with modern anatomy a point of discussion rather than a given. Four questions arise from this debate: (a) What is modern behavior? (b) Is the emergence of modern behavior sudden or more gradual? (c) Is modern behavior unique to modern humans or more widely shared with other species, most notably the Neandertals? (d) Is the emergence of modern behavior primarily the result of new cognitive abilities or social, cultural, demographic, and historic factors? This review briefly addresses each of these questions and in the process offers some thoughts on the current state of the debate.
Preindustrial Markets and Marketing: Archaeological Perspectives
Authors: Feinman Gary M. , Garraty Christopher P.
Published: September 2010

Markets are key contemporary institutions, yet there is little agreement concerning their history or diversity. To complicate matters, markets have been considered by different academic disciplines that approach the nature of such exchange systems from diametrically opposed perspectives that impede cross-disciplinary dialogue. This paper reviews the theoretical and methodological issues surrounding the detection, development, and significance of markets in the preindustrial past. We challenge both the view that marketing is natural and the perspective that market exchange is unique to modern capitalist contexts. Both of these frameworks fail to recognize that past and present market activities are embedded in their larger societal contexts, albeit in different ways that can be understood only if examined through a broadly shared theoretical lens. We examine the origins, change, and diversity of preindustrial markets, calling for multiscalar, cross-disciplinary approaches to investigate the long-term history of this economic institution.
Role of phospholemman phosphorylation sites in mediating kinase-dependent regulation of the Na+-K+-ATPase
Authors: Han Fei , Bossuyt Julie , Martin Jody L. , Despa Sanda , Bers Donald M.
Published: September 2010

Phospholemman (PLM) is a major target for phosphorylation mediated by both PKA (at Ser68) and PKC (at both Ser63 and Ser68) in the heart. In intact cardiac myocytes, PLM associates with and inhibits Na+-K+-ATPase (NKA), mainly by reducing its affinity for internal Na+. The inhibition is relieved upon PLM phosphorylation by PKA or PKC. The aim here was to distinguish the role of the Ser63 and Ser68 PLM phosphorylation sites in mediating kinase-induced modulation of NKA function. We expressed wild-type (WT) PLM and S63A, S68A, and AA (Ser63 and Ser68 to alanine double mutant) PLM mutants in HeLa cells that stably express rat NKA-α1 and we measured the effect of PKA and PKC activation on NKA-mediated intracellular Na+ concentration decline. PLM expression (WT or mutant) significantly decreased the apparent NKA affinity for internal Na+ and had no significant effect on the maximum pump rate ( Vmax). PKA activation with forskolin (20 μM) restored NKA Na+ affinity in cells expressing WT but not AA PLM and did not affect Vmax in either case. Similarly, PKC activation with 300 nM phorbol 12,13-dibutyrate increased NKA Na+ affinity in cells expressing WT, S63A, and S68A PLM and had no effect in cells expressing AA PLM. Neither forskolin nor phorbol 12,13-dibutyrate affected NKA function in the absence of PLM. We conclude that PLM phosphorylation at either Ser63 or Ser68 is both necessary and sufficient for completely relieving the PLM-induced NKA inhibition.
Substrate stiffening promotes endothelial monolayer disruption through enhanced physical forces
Authors: Krishnan Ramaswamy , Klumpers Darinka D. , Park Chan Y. , Rajendran Kavitha , Trepat Xavier , van Bezu Jan , van Hinsbergh Victor W. M. , Carman Christopher V. , Brain Joseph D. , Fredberg Jeffrey J. , Butler James P. , van Nieuw Amerongen Geerten P.
Published: September 2010

A hallmark of many, sometimes life-threatening, inflammatory diseases and disorders is vascular leakage. The extent and severity of vascular leakage is broadly mediated by the integrity of the endothelial cell (EC) monolayer, which is in turn governed by three major interactions: cell-cell and cell-substrate contacts, soluble mediators, and biomechanical forces. A potentially critical but essentially uninvestigated component mediating these interactions is the stiffness of the substrate to which the endothelial monolayer is adherent. Accordingly, we investigated the extent to which substrate stiffening influences endothelial monolayer disruption and the role of cell-cell and cell-substrate contacts, soluble mediators, and physical forces in that process. Traction force microscopy showed that forces between cell and cell and between cell and substrate were greater on stiffer substrates. On stiffer substrates, these forces were substantially enhanced by a hyperpermeability stimulus (thrombin, 1 U/ml), and gaps formed between cells. On softer substrates, by contrast, these forces were increased far less by thrombin, and gaps did not form between cells. This stiffness-dependent force enhancement was associated with increased Rho kinase activity, whereas inhibition of Rho kinase attenuated baseline forces and lessened thrombin-induced inter-EC gap formation. Our findings demonstrate a central role of physical forces in EC gap formation and highlight a novel physiological mechanism. Integrity of the endothelial monolayer is governed by its physical microenvironment, which in normal circumstances is compliant but during pathology becomes stiffer.
mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy
Authors: Song Xiaoxiao , Kusakari Yoichiro , Xiao Chun-Yang , Kinsella Stuart D. , Rosenberg Michael A. , Scherrer-Crosbie Marielle , Hara Kenta , Rosenzweig Anthony , Matsui Takashi
Published: September 2010

Previous studies have suggested that inhibition of the mammalian target of rapamycin (mTOR) by rapamycin suppresses myocardial hypertrophy. However, the role of mTOR in the progression of cardiac dysfunction in pathological hypertrophy has not been fully defined. Interestingly, recent reports indicate that the inflammatory response, which plays an important role in the development of heart failure, is enhanced by rapamycin under certain conditions. Our aim in this study was to determine the influence of mTOR on pathological hypertrophy and to assess whether cardiac mTOR regulates the inflammatory response. We generated transgenic mice with cardiac-specific overexpression of wild-type mTOR (mTOR-Tg). mTOR-Tg mice were protected against cardiac dysfunction following left ventricular pressure overload induced by transverse aortic constriction (TAC) ( P < 0.01) and had significantly less interstitial fibrosis compared with littermate controls (WT) at 4 wk post-TAC ( P < 0.01). In contrast, TAC caused cardiac dysfunction in WT. At 1 wk post-TAC, the proinflammatory cytokines interleukin (IL)-1β and IL-6 were significantly increased in WT mice but not in mTOR-Tg mice. To further characterize the effects of mTOR activation, we exposed HL-1 cardiomyocytes transfected with mTOR to lipopolysaccharide (LPS). mTOR overexpression suppressed LPS-induced secretion of IL-6 ( P < 0.001), and the mTOR inhibitors rapamycin and PP242 abolished this inhibitory effect of mTOR. In addition, mTOR overexpression reduced NF-κB-regulated transcription in HL-1 cells. These data suggest that mTOR mitigates adverse outcomes of pressure overload and that this cardioprotective effect of mTOR is mediated by regulation of the inflammatory reaction.
Endothelial metallothionein expression and intracellular free zinc levels are regulated by shear stress
Authors: Conway Daniel E. , Lee Sungmun , Eskin Suzanne G. , Shah Ankit K. , Jo Hanjoong , McIntire Larry V.
Published: September 2010

We examined the effects of fluid shear stress on metallothionein (MT) gene and protein expression and intracellular free zinc in mouse aorta and in human umbilical vein endothelial cells (HUVECs). Immunostaining of the endothelial surface of mouse aorta revealed increased expression of MT protein in the lesser curvature of the aorta relative to the descending thoracic aorta. HUVECs were exposed to high steady shear stress (15 dyn/cm2), low steady shear stress (1 dyn/cm2), or reversing shear stress (mean of 1 dyn/cm2, 1 Hz) for 24 h. Gene expression of three MT-1 isoforms, MT-2A, and zinc transporter-1 was upregulated by low steady shear stress and reversing shear stress. HUVECs exposed to 15 dyn/cm2 had increased levels of free zinc compared with cells under other shear stress regimes and static conditions. The increase in free zinc was partially blocked with an inhibitor of nitric oxide synthesis, suggesting a role for shear stress-induced endothelial nitric oxide synthase activity. Cells subjected to reversing shear stress in zinc-supplemented media (50 μM ZnSO4) had increased intracellular free zinc, reduced surface intercellular adhesion molecule-1 expression, and reduced monocyte adhesion compared with cells exposed to reversing shear stress in normal media. The sensitivity of intracellular free zinc to differences in shear stress suggests that intracellular zinc levels are important in the regulation of the endothelium and in the progression of vascular disease.
α-Synuclein binds the KATP channel at insulin-secretory granules and inhibits insulin secretion
Authors: Geng Xuehui , Lou Haiyan , Wang Jian , Li Lehong , Swanson Alexandra L. , Sun Ming , Beers-Stolz Donna , Watkins Simon , Perez Ruth G. , Drain Peter
Published: September 2010

α-Synuclein has been studied in numerous cell types often associated with secretory processes. In pancreatic β-cells, α-synuclein might therefore play a similar role by interacting with organelles involved in insulin secretion. We tested for α-synuclein localizing to insulin-secretory granules and characterized its role in glucose-stimulated insulin secretion. Immunohistochemistry and fluorescent sulfonylureas were used to test for α-synuclein localization to insulin granules in β-cells, immunoprecipitation with Western blot analysis for interaction between α-synuclein and KATP channels, and ELISA assays for the effect of altering α-synuclein expression up or down on insulin secretion in INS1 cells or mouse islets, respectively. Differences in cellular phenotype between α-synuclein knockout and wild-type β-cells were found by using confocal microscopy to image the fluorescent insulin biosensor Ins-C-emGFP and by using transmission electron microscopy. The results show that anti-α-synuclein antibodies labeled secretory organelles within β-cells. Anti-α-synuclein antibodies colocalized with KATP channel, anti-insulin, and anti-C-peptide antibodies. α-Synuclein coimmunoprecipitated in complexes with KATP channels. Expression of α-synuclein downregulated insulin secretion at 2.8 mM glucose with little effect following 16.7 mM glucose stimulation. α-Synuclein knockout islets upregulated insulin secretion at 2.8 and 8.4 mM but not 16.7 mM glucose, consistent with the depleted insulin granule density at the β-cell surface membranes observed in these islets. These findings demonstrate that α-synuclein interacts with KATP channels and insulin-secretory granules and functionally acts as a brake on secretion that glucose stimulation can override. α-Synuclein might play similar roles in diabetes as it does in other degenerative diseases, including Alzheimer's and Parkinson's diseases.
Sustained glucagon-like peptide-2 infusion is required for intestinal adaptation, and cessation reverses increased cellularity in rats with intestinal failure
Authors: Koopmann Matthew C. , Chen Xueyan , Holst Jens J. , Ney Denise M.
Published: September 2010

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived hormone that is a proposed treatment for human short bowel syndrome (SBS). The objective was to determine how the timing, duration, and cessation of GLP-2 administration affect intestinal adaptation and enterocyte kinetics in a rat model of human SBS that results in intestinal failure requiring total parenteral nutrition (TPN). Rats underwent 60% jejunoileal resection plus cecectomy and jugular vein cannulation and were maintained exclusively with TPN for 18 days in these treatments: TPN control (no GLP-2); sustained GLP-2 (1–18 days); early GLP-2 (1–7 days, killed at 7 or 18 days); and delayed GLP-2 (12–18 days). Body weight gain was similar across groups, and plasma bioactive GLP-2 was significantly increased with coinfusion of GLP-2 (100 μg·kg−1·day−1) with TPN. GLP-2-treated rats showed significant increases in duodenum and jejunum mucosal dry mass, protein, DNA, and sucrase activity compared with TPN control. The increased jejunum cellularity reflected significantly decreased apoptosis and increased crypt mitosis and crypt fission due to GLP-2. When GLP-2 infusion stopped at 7 days, these effects were reversed at 18 days. Sustained GLP-2 infusion significantly increased duodenum length and decreased 18-day mortality to 0% from 37.5% deaths in TPN control ( P = 0.08). Colon proglucagon expression quantified by real-time RT-qPCR was increased in TPN controls and attenuated by GLP-2 infusion; jejunal expression of the GLP-2 receptor did not differ among groups. In summary, early, sustained GLP-2 infusion reduces mortality, induces crypt fission, and is required for intestinal adaptation, whereas cessation of GLP-2 reverses gains in mucosal cellularity in a rat model of intestinal failure.
Impaired ventilatory acclimatization to hypoxia in female mice overexpressing erythropoietin: unexpected deleterious effect of estradiol in carotid bodies
Authors: Gassmann Max , Pfistner Christine , Doan Van Diep , Vogel Johannes , Soliz Jorge
Published: September 2010

Apart from enhancing the production of red blood cells, erythropoietin (Epo) alters the ventilatory response when oxygen supply is reduced. We recently demonstrated that Epo's beneficial effect on the ventilatory response to acute hypoxia is sex dependent, with female mice being better able to cope with reduced oxygenation. In the present work, we hypothesized that ventilatory acclimatization to chronic hypoxia (VAH) in transgenic female mice (Tg6) harboring high levels of Epo in the brain and blood will also be improved compared with wild-type (WT) animals. Surprisingly, VAH was blunted in Tg6 female mice. To define whether this phenomenon had a central (brain stem respiratory centers) and/or peripheral (carotid bodies) origin, a bilateral transection of carotid sinus nerve (chemodenervation) was performed. This procedure allowed the analysis of the central response in the absence of carotid body information. Interestingly, chemodenervation restored the VAH in Tg6 mice, suggesting that carotid bodies were responsible for the blunted response. Coherently with this observation, the sensitivity to oxygen alteration in arterial blood (Dejour test) after chronic hypoxia was lower in transgenic carotid bodies compared with the WT control. As blunted VAH occurred in female but not male transgenic mice, the involvement of sex female steroids was obvious. Indeed, measurement of sexual female hormones revealed that the estradiol serum level was 4 times higher in transgenic mice Tg6 than in WT animals. While ovariectomy decreased VAH in WT females, this treatment restored VAH in Tg6 female mice. In line with this observation, injections of estradiol in ovariectomized Tg6 females dramatically reduced the VAH. We concluded that during chronic hypoxia, estradiol in carotid bodies suppresses the Epo-mediated elevation of ventilation. Considering the increased application of recombinant Epo for a variety of disorders, our data imply the need to take the patient's hormonal status into consideration.
A metabolomics approach to elucidate effects of food deprivation in juvenile rainbow trout (Oncorhynchus mykiss)
Authors: Kullgren Andreas , Samuelsson Linda M. , Larsson D. G. Joakim , Björnsson Björn Thrandur , Bergman Elisabeth Jönsson
Published: September 2010

The aim of this study was to evaluate whether NMR-based metabolomics is a suitable method to generate an integrated view on metabolic processes during food deprivation in salmonid fish. Juvenile rainbow trout ( Oncorhynchus mykiss ) weighing 43–115 g were either fed ad libitum or deprived of food for 28 days at 10°C to investigate catabolic effects on energy reserves and metabolite patterns. The NMR analysis of plasma, liver, and muscle extracts revealed significant fasting-induced changes in the metabolome. Altered plasma lipoprotein levels and tissue-specific patterns of fatty acid mobilization were the most prominent responses, emphasizing the role of lipids as the primary energy source during fasting. In plasma, very-low-density lipoprotein levels increased in food-deprived fish compared with fed fish, whereas levels of high-density lipoprotein decreased. Signs of muscle protein catabolism were also observed as changes in the alanine dynamics. The results further suggest that mechanisms to preserve liver glycogen are present in the food-deprived fish. This study thus demonstrates the utility of NMR-based metabolomics of tissue extracts and plasma to describe the integrated metabolic status of fish.
The continuum of hybrid IIX/IIB fibers in normal mouse muscles: MHC isoform proportions and spatial distribution within single fibers
Authors: Zhang Min Yi , Zhang Wei Jie , Medler Scott
Published: September 2010

Although skeletal muscle fiber types are often defined as belonging to discrete categories, many muscles possess fibers with intermediate phenotypes. These hybrid fiber types can be identified by their expression of two or more myosin heavy chain (MHC) isoforms within the same single fiber. In mouse muscles, the most common hybrid fibers are those coexpressing the IIX and IIB MHC isoforms. In the present study, we focused on these IIX/IIB fibers from normal mouse muscles to determine the relative proportions of MHC isoforms at both the protein and mRNA levels and to examine the longitudinal distribution of isoforms within single fibers. We found that IIX/IIB hybrids represent ∼25 and 50% of the fibers in the mouse tibialis anterior and brachioradialis, respectively. The relative proportion of the IIX and IIB isoforms in these fibers spans a continuum, from predominantly IIB-like hybrids to IIX-like hybrids. Quantitative assessment of mRNA levels using real-time PCR from single fibers indicated that IIB expression dominated over IIX expression in most fibers and that a general correlation existed between mRNA isoform levels and MHC protein content. However, the match between mRNA levels and protein content was not precise. Finally, we measured MHC isoform proportions in adjacent fiber segments and discovered that ∼30% of hybrids possessed significant differences in isoform content along their length. In some instances, the muscle fiber type as defined by MHC content changed completely along the length of a fiber. This pattern of asymmetrical MHC isoform content along the length of single fibers suggests that the multiple myonuclei of a muscle fiber may express distinct myofibrillar isoforms in an uncoordinated fashion.
Inhalation heterogeneity from subresidual volumes in elite divers
Authors: Muradyan Iga , Loring Stephen H. , Ferrigno Massimo , Lindholm Peter , Topulos George P. , Patz Samuel , Butler James P.
Published: September 2010

Punctate reopening of the lung from subresidual volumes (sub-RV) is commonly observed in excised lung preparations, either degassed or collapsed to zero transpulmonary pressure, and in the course of reinflation of human lungs when the chest is open, secondary to traumatic or surgical pneumothoraxes. In the course of physiological studies on two elite breath-hold divers, who are able to achieve lung volumes well below traditional RV with glossopharyngeal exsufflation, we used MRI lung imaging with inhaled hyperpolarized 129Xe to visualize ventilatory patterns. We observed strikingly inhomogeneous inhalation patterns with small inhalation volumes from sub-RV, consistent with reopening of frankly closed airways. On the other hand, two age-matched and two older controls, inhaling from just above RV, showed a much more homogeneous pattern. Our results demonstrate the concept of frank airway closure below RV in young healthy adults with an intact chest wall.
Chronic Dysfunction of Astrocytic Inwardly Rectifying K+ Channels Specific to the Neocortical Epileptic Focus After Fluid Percussion Injury in the Rat
Authors: Stewart Tessandra H. , Eastman Clifford L. , Groblewski Peter A. , Fender Jason S. , Verley Derek R. , Cook David G. , D'Ambrosio Raimondo
Published: September 2010

Astrocytic inwardly rectifying K+ currents ( IKIR) have an important role in extracellular K+ homeostasis, which influences neuronal excitability, and serum extravasation has been linked to impaired KIR-mediated K+ buffering and chronic hyperexcitability. Head injury induces acute impairment in astroglial membrane IKIR and impaired K+ buffering in the rat hippocampus, but chronic spontaneous seizures appear in the perilesional neocortex—not the hippocampus—in the early weeks to months after injury. Thus we examined astrocytic KIR channel pathophysiology in both neocortex and hippocampus after rostral parasaggital fluid percussion injury (rpFPI). rpFPI induced greater acute serum extravasation and metabolic impairment in the perilesional neocortex than in the underlying hippocampus, and in situ whole cell recordings showed a greater acute loss of astrocytic IKIR in neocortex than hippocampus. IKIR loss persisted through 1 mo after injury only in the neocortical epileptic focus, but fully recovered in the hippocampus that did not generate chronic seizures. Neocortical cell-attached recordings showed no loss or an increase of IKIR in astrocytic somata. Confocal imaging showed depletion of KIR4.1 immunoreactivity especially in processes—not somata—of neocortical astrocytes, whereas hippocampal astrocytes appeared normal. In naïve animals, intracortical infusion of serum, devoid of coagulation-mediating thrombin activity, reproduces the effects of rpFPI both in vivo and at the cellular level. In vivo serum infusion induces partial seizures similar to those induced by rpFPI, whereas bath-applied serum, but not dialyzed albumin, rapidly silenced astrocytic KIR membrane currents in whole cell and cell-attached patch-clamp recordings in situ. Thus both acute impairment in astrocytic IKIR and chronic spontaneous seizures typical of rpFPI are reproduced by serum extravasation, whereas the chronic impairment in astroglial IKIR is specific to the neocortex that develops the epileptic focus.
Origins of Spontaneous Firing of Motor Units in the Spastic–Paretic Biceps Brachii Muscle of Stroke Survivors
Authors: Mottram C. J. , Wallace C. L. , Chikando C. N. , Rymer W. Z.
Published: September 2010

One potential expression of altered motoneuron excitability following a hemispheric stroke is the spontaneous unit firing (SUF) of motor units at rest. The elements contributing to this altered excitability could be spinal descending pathways, spinal interneuronal networks, afferent feedback, or intrinsic motoneuron properties. Our purpose was to examine the characteristics of spontaneous discharge in spastic–paretic and contralateral muscles of hemiparetic stroke survivors, to determine which of these mechanisms might contribute. To achieve this objective, we examined the statistics of spontaneous discharge of individual motor units and we conducted a coherence analyses on spontaneously firing motor unit pairs. The presence of significant coherence between units might indicate a common driving source of excitation to multiple motoneurons from descending pathways or regional interneurons, whereas a consistent lack of coherence might favor an intrinsic cellular mechanism of hyperexcitability. Spontaneous firing of motor units (i.e., ongoing discharge in the absence of an ongoing stimulus) was observed to a greater degree in spastic–paretic muscles (following 83.2 ± 16.7% of ramp contractions) than that in contralateral muscles (following just 14.1 ± 10.5% of ramp contractions; P < 0.001) and was not observed at all in healthy control muscle. The average firing rates of the spontaneously firing units were 8.4 ± 1.8 pulses/s (pps) in spastic–paretic muscle and 9.6 ± 2.2 pps in contralateral muscle ( P < 0.001). In 37 instances ( n = 63 pairs), we observed spontaneous discharge of two or more motor units simultaneously in spastic–paretic muscle. Seventy percent of the dually firing motor unit pairs exhibited significant coherence ( P < 0.001) in the 0- to 4-Hz bandwidth (average peak coherence: 0.14 ± 0.13; range: 0.01–0.75) and 22% of pairs exhibited significant coherence ( P < 0.001) in the 15- to 30-Hz bandwidth (average peak coherence: 0.07 ± 0.06; range: 0.01–0.31). We suggest that the spontaneous firing was likely not attributable solely to enhanced intrinsic motoneuron activation, but attributable, at least in part, to a low-level excitatory synaptic input to the resting spastic–paretic motoneuron pool, possibly from regional or supraspinal centers.
Spatiotemporal Dynamics of Rhythmic Spinal Interneurons Measured With Two-Photon Calcium Imaging and Coherence Analysis
Authors: Kwan Alex C. , Dietz Shelby B. , Zhong Guisheng , Harris-Warrick Ronald M. , Webb Watt W.
Published: September 2010

In rhythmic neural circuits, a neuron often fires action potentials with a constant phase to the rhythm, a timing relationship that can be functionally significant. To characterize these phase preferences in a large-scale, cell type–specific manner, we adapted multitaper coherence analysis for two-photon calcium imaging. Analysis of simulated data showed that coherence is a simple and robust measure of rhythmicity for calcium imaging data. When applied to the neonatal mouse hindlimb spinal locomotor network, the phase relationships between peak activity of >1,000 ventral spinal interneurons and motor output were characterized. Most interneurons showed rhythmic activity that was coherent and in phase with the ipsilateral motor output during fictive locomotion. The phase distributions of two genetically identified classes of interneurons were distinct from the ensemble population and from each other. There was no obvious spatial clustering of interneurons with similar phase preferences. Together, these results suggest that cell type, not neighboring neuron activity, is a better indicator of an interneuron's response during fictive locomotion. The ability to measure the phase preferences of many neurons with cell type and spatial information should be widely applicable for studying other rhythmic neural circuits.
The Nervous System Uses Nonspecific Motor Learning in Response to Random Perturbations of Varying Nature
Authors: Wei Kunlin , Wert Daniel , Körding Konrad
Published: September 2010

We constantly make small errors during movement and use them to adapt our future movements. Movement experiments often probe this error-driven learning by perturbing movements and analyzing the after-effects. Past studies have applied perturbations of varying nature such as visual disturbances, position- or velocity-dependent forces and modified inertia properties of the limb. However, little is known about how the specific nature of a perturbation influences subsequent movements. For a single perturbation trial, the nature of a perturbation may be highly uncertain to the nervous system, given that it receives only noisy information. One hypothesis is that the nervous system can use this rough estimate to partially correct for the perturbation on the next trial. Alternatively, the nervous system could ignore uncertain information about the nature of the perturbation and resort to a nonspecific adaptation. To study how the brain estimates and responds to incomplete sensory information, we test these two hypotheses using a trial-by-trial adaptation experiment. On each trial, the nature of the perturbation was chosen from six distinct types, including a visuomotor rotation and different force fields. We observed that corrective forces aiming to oppose the perturbation in the following trial were independent of the nature of the perturbation. Our results suggest that the nervous system uses a nonspecific strategy when it has high uncertainty about the nature of perturbations during trial-by-trial learning.
Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis
Authors: Ungethuem U. , Haeupl T. , Witt H. , Koczan D. , Krenn V. , Huber H. , von Helversen T. M. , Drungowski M. , Seyfert C. , Zacher J. , Pruss A. , Neidel J. , Lehrach H. , Thiesen H. J. , Ruiz P. , Bläß S.
Published: September 2010

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced interpatient heterogeneity. To characterize RA at the molecular level and to uncover pathomechanisms, we performed genome-wide gene expression analysis. We identified a set of 1,054 genes significantly deregulated in pair-wise comparisons between RA and osteoarthritis (OA) patients, RA and normal donors (ND), or OA and ND. Correlation analysis revealed gene sets regulated identically in all three groups. As a prominent example secreted phosphoprotein 1 (SPP1) was identified to be significantly upregulated in RA compared with both OA and ND. SPP1 expression was found to correlate with genes expressed during an inflammatory response, T-cell activation and apoptosis, suggesting common underlying regulatory networks. A subclassification of RA patients was achieved on the basis of proteoglycan 4 (PRG4) expression, distinguishing PRG4 high and low expressors and reflecting the heterogeneity of the disease. In addition, we found that low PRG4 expression was associated with a more aggressive disease stage, which is in accordance with PRG4 loss-of-function mutations causing camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Altogether we provide evidence for molecular signatures of RA and RA subclasses, sets of new candidate genes as well as for candidate gene networks, which extend our understanding of disease mechanisms and may lead to an improved diagnosis.
Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice
Authors: Li Renhua H. , Churchill Gary A.
Published: September 2010

Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent of diet, whereas other strains, including DBA2/J, show marked changes in plasma HDL. To explore this phenomenon further, we used publicly available data from a C57BL/6J × DBA/2J intercross to identify genetic factors that associate with HDL under high-fat diet conditions. Our analysis identified an epistatic interaction that plays a role in the buffering of HDL levels in C57BL/6J mice, and we have identified Arl4d as a candidate gene that mediates this effect. Structural modeling further elucidates the interaction of genetic factors that contribute to the robustness of HDL in response to high-fat diet in the C57BL/6J strain.