bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study of Experiential Technology and Scientific Technology, Exemplified by Chinese and Western Medicine
Authors: Song Tian
Published: May 2011

Experience and science, being the two sources of technology, have different focuses. In experiential technology, techniques and skills are emphasized while in scientific technology tool or equipment. Experiential technology is generally regarded as local knowledge, and scientific technology universal. Traditional Chinese medicine is an experiential technology. In contrast, Western medicine is set up as a scientific technology with great efforts. Through the comparison of these two medicines, this paper attempts to illustrate the difference between the two technologies and in turn, the difference between these two medicines by defining these two technologies. Finally, this paper further investigates the special values of Chinese medicine. Making use of the SSK theory, this paper deconstructs the idea of universality of science, and argues that, the universality is the feature that science pursues, but not what it already has. With more historical evidence, experiential technology is more stable, while scientific technology is less stable because it updates quickly, and often changes reversely.
Implications of the Dutch Book: Following Ramsey’s Axioms
Authors: Wei Xiong
Published: May 2011

The Dutch Book Argument shows that an agent will lose surely in a gamble (a Dutch Book is made) if his degrees of belief do not satisfy the laws of the probability. Yet a question arises here: What does the Dutch Book imply? This paper firstly argues that there exists a utility function following Ramsey’s axioms. And then, it explicates the properties of the utility function and degree of belief respectively. The properties show that coherence in partial beliefs for Subjective Bayesianism means that the degree of belief, representing a belief ordering, satisfies the laws of probability, and that coherence in preferences means that the preferences are represented by expected utilities. A coherent belief ordering and a utility scale induce a coherent preference ordering; a coherent preference ordering induces a coherent belief ordering which can be uniquely represented by a degree-of-belief function. The preferences (values) and beliefs are both incoherent or disordered if a Dutch Book is made.
Transcriptional modulation by VIP: a rational target against inflammatory disease
Authors: Ibrahim Hiba , Barrow Paul , Foster Neil
Published: May 2011

Vasoactive intestinal peptide (VIP) is a pleiotropic, highly conserved, peptide found in many different biological systems throughout invertebrate phyla. VIP is produced by cells of the immune system but also inhibits many different inflammatory products produced by these immune cells, including cytokines and chemokines. VIP inhibits these immune mediators by affecting transcriptional regulators such as NFκB and activator protein 1 which transcribes genes responsible for the production of inflammatory mediators in response to pathogens or cytokines. In this review, the therapeutic potential of VIP will be discussed in the context of transcriptional regulation of immune cells in in vitro and in vivo animal models.
Relation of body composition to daily physical activity in free-living Japanese adult women
Authors: Park Jonghoon , Ishikawa-Takata Kazuko , Tanaka Shigeho , Hikihara Yuki , Ohkawara Kazunori , Watanabe Shaw , Miyachi Motohiko , Morita Akemi , Aiba Naomi , Tabata Izumi
Published: May 2011

The objective of the present study was to investigate the relationship between the indices of body size such as BMI, fat-free mass index (FFMI, FFM/height2), fat mass index (FMI, FM/height2), and body fat percentage (%BF), and physical activities assessed by the doubly-labelled water (DLW) method and an accelerometer in free-living Japanese adult women. We conducted a cross-sectional study in 100 female subjects ranging in age from 31 to 69 years. Subjects were classified in quartiles of BMI, FFMI, FMI and %BF. Daily walking steps and the duration of light to vigorous physical activity were simultaneously assessed by an accelerometer for the same period as the DLW experiment. Only physical activity-related energy expenditure (PAEE)/FFM and PAEE/body weight (BW) decreased in the highest quartile of BMI. Physical activity level, PAEE/FFM and PAEE/BW decreased in the highest quartile of FMI and %BF, whereas they were not different among quartiles of FFMI. Daily walking steps and the duration of moderate- and vigorous-intensity physical activities decreased or tended to decrease in the highest quartile of FMI and %BF, but did not differ among quartiles of FFMI and BMI. These results clearly showed that Japanese adult women with higher fat deposition obviously had a low level of physical activities assessed by both the DLW method and accelerometry, but those with larger BMI had lower PAEE/FFM and PAEE/BW only. Our data suggest that the relationship between obesity and daily physical activities should be discussed using not only BMI but also FMI or %BF.
Migrant Workers in the Middle East: Introduction
Authors: Parthasarathi Prasannan , Quataert Donald
Published: May 2011

Transnational labor migration is one of the most visible features of our globalizing world. The International Organization for Migration estimates that there are 214 million migrant workers crossing national borders in the world today. Migration both in and to the Middle East constitutes an important part of this movement of laborers and has deep roots. In the mid-fifteenth century, workers across a broad spectrum of occupations, including stevedores, boatmen, and bakers, trekked from areas in eastern and central Anatolia to the new imperial Ottoman capital, Istanbul, where they lived and worked for months and even years. Workers from outside the Middle East also have been part of the fabric of life in the region for several centuries, the slave trade from sub-Saharan Africa, which long supplied labor for a variety of purposes, being one of the most notable. Migrant workers took on new significance in the twentieth century, especially after the oil price hikes of 1973. Today the nations on the Arabian Peninsula, the destination for most workers, have the highest ratio of migrants to locals in the world.
Differences in Workers' Narratives of Contention in Two Central Indian Towns
Authors: Nair Manjusha
Published: May 2011

Contract work in India, though legally regulated by a 1970 Act, is widespread and mostly unrecognized. With the implementation of neoliberal policies in India since the 1990s, contract work has become the norm. There are now few spaces in which contract workers can get redress through the legal system. Using oral history narratives of contract workers' participation in a labor movement, this article shows how narratives of contention differ in the rendering of agency, success, and future, between one group of contract workers employed in the 1970s in a state-owned mine and another employed in the 1990s in an industrial area owned by private and foreign capital. The evidence for the article is ethnographic, collected in Chhattisgarh region in central India. This article suggests that these workers' narratives show the transformation in practices of citizenship, resistance, and militancy in India over time. Such differences are essential in understanding phenomena like the resurgence of the Maoist movement in Chhattisgarh.
The Turn of the Gulf Tide: Empire, Nationalism, and South Asian Labor Migration to Iraq, c. 1900–1935
Authors: Tetzlaff Stefan
Published: May 2011

This paper looks at various circumstances of labor migration from South Asia to Iraq between 1900 and 1935. It stresses that inter-regional labor migration existed to varying degrees before, during, and after the First World War. This was predominantly a function of longstanding commercial ties besides the wartime engagement. At another level, the article offers an interpretation of how labor migration intersects with imperial formations as well as nationalisms evolving in both realms. It argues that the issue of migration to Iraq has to be seen in the context of a plethora of interventions and demands in the relationship between India and the Persian Gulf region over a much longer time period.
A framework for the analysis and synthesis of 3D dynamic human gait
Authors: Firmani Flavio , Park Edward J.
Published: May 2011

A comprehensive framework for the analysis and synthesis of 3D human gait is presented. The framework consists of a realistic morphological representation of the human body involving 40 degrees of freedom and 17 body segments. Through the analysis of human gait, the joint reaction forces/moments can be estimated and parameters associated with postural stability can be quantified. The synthesis of 3D human gait is a complicated problem due to the synchronisation of a large number of joint variables. Herein, the framework is employed to reconstruct a dynamically balanced gait cycle and develop sets of reference trajectories that can be used for either the assessment of human mobility or the control of mechanical ambulatory systems. The gait cycle is divided into eight postural configurations based on particular gait events. Gait kinematic data is used to provide natural human movements. The balance stability analysis is performed with various ground reference points. The proposed reconstruction of the gait cycle requires two optimisation steps that minimise the error distance between evaluated and desired gait and balance constraints. The first step (quasi-static motion) is used to approximate the postural configurations to a region close to the second optimisation step target while preserving the natural movements of human gait. The second step (dynamic motion) considers a normal speed gait cycle and is solved using the spacetime constraint method and a global optimisation algorithm. An experimental validation of the generated reference trajectories is carried out by comparing the paths followed by 19 optical markers of a motion tracking system with the paths of the corresponding node points on the model.
GENERALIZED EXTREME SHOCK MODELS WITH A POSSIBLY INCREASING THRESHOLD
Authors: Cirillo Pasquale , Hüsler Jürg
Published: May 2011

We propose a generalized extreme shock model with a possibly increasing failure threshold. Although standard models assume that the crucial threshold for the system might only decrease over time, because of weakening shocks and obsolescence, we assume that, especially at the beginning of the system's life, some strengthening shocks might increase the system tolerance to large shock. This is, for example, the case of turbines’ running-in in the field of engineering. On the basis of parametric assumptions, we provide theoretical results and derive some exact and asymptotic univariate and multivariate distributions for the model. In the last part of the article we show how to link this new model to some nonparametric approaches proposed in the literature.
Importance of nest attributes in the conservation of endemic birds of the Juan Fernández Archipelago, Chile
Authors: HAHN INGO J. , VERGARA PABLO M. , RÖMER UWE
Published: May 2011

Understanding the particular nesting ecology of island endemic species represents the first step in identifying suitable micro-habitats and establishing efficient management programmes. This could become even more important when island bird assemblages are prone to invasion by ecologically similar species that may eventually cause niche compression or the extirpation of species already present on the island. In this study we describe the nesting ecology of both native and introduced landbird species of the Juan Fernández Islands and determine the extent to which native species could be negatively affected by alien competitors. A total of 119 nests belonging to the 11 resident landbird species were analysed. Landbirds exhibited a wide range of nesting habitat preferences on the different islands, covering different vegetation types, altitudes and ecosystems. By means of a cluster analysis we determined that competition between alien and endemic species apparently does not represent an important factor affecting resource use by endemic birds. Endemic landbirds preferred sites comparatively higher above the ground, with a greater slope and a larger level of shelter, than alien species. The introduced hummingbird, the Green-backed FirecrownSephanoides sephaniodes, had different nesting preferences to the endemic Juan Fernandez FirecrownS. fernandensis, whereas the House SparrowPasser domesticusselected nest sites located in populated areas, suggesting that both alien species may not be competing with endemic passerines for nest sites. However, urgent measures are necessary to reduce the potential predation risk on Juan Fernandez Firecrown nests by the alien Austral ThrushTurdus falcklandii.
New heterodontosaurid specimens from the Lower Jurassic of southern Africa and the early ornithischian dinosaur radiation
Authors: Porro Laura B. , Butler Richard J. , Barrett Paul M. , Moore-Fay Scott , Abel Richard L.
Published: May 2011

Heterodontosaurids are poorly understood early ornithischian dinosaurs with extensive geographic and stratigraphic ranges. The group is best known from the Lower Jurassic upper ‘Stormberg Group’ (upper Elliot and Clarens formations) of southern Africa, previously represented by at least three distinct species and ten described specimens. This paper describes four additional heterodontosaurid specimens from southern Africa. A partial skull of a large individual of Heterodontosaurus tucki (NM QR 1788) is approximately 70 longer than that of the type specimen of Heterodontosaurus, and provides new information on allometric changes in mandibular morphology during growth in this taxon. It is the largest known heterodontosaurid cranial specimen, representing an individual approximately 1·75 metres in length, and perhaps 10 kg in body mass. NHMUK R14161 is a partial skull that appears to differ from all other heterodontosaurids on the basis of the proportions of the dentaries, and may represent an unnamed new taxon. Two additional partial skulls (NHMUK RU C68, NHMUK RU69) are referred to cf. Lycorhinus. At least four, and possibly five or more, heterodontosaurid species are present in the upper ‘Stormberg’. This high diversity may have been achieved by dietary niche partitioning, and suggests an adaptive radiation of small-bodied ornithischians following the end Triassic extinctions.
A new dicynodont–archosaur assemblage from the Late Triassic (Carnian) of Poland
Authors: Sulej Tomasz , Bronowicz Robert , Tałanda Mateusz , Niedźwiedzki Grzegorz
Published: May 2011

This paper reports a new assemblage from the Late Triassic (mid–late Carnian) at Woźniki near Częstochowa (Poland). The Woźniki vertebrate assemblage is similar to that of Lisowice–Lipie Śląskie, a new locality bearing vertebrates from latest Triassic (latest Norian–early Rhaetian) strata of southern Poland, in the presence of dicynodonts, shark spines, plagiosaurs and a cyclotosaur, but conchostracans and bivalves are similar to those from the Krasiejów site (late Carnian). The most complete specimen from Woźniki belongs to a dicynodont, and consists of cranial and postcranial bones of a single individual. It demonstrates that large dicynodonts were part of the Late Triassic vertebrate assemblage in Central Europe. Numerous tetrapod tracks and traces are associated with skeletal fossils at Woźniki.
Ist Neurofeedbacktraining eine wirksame Therapiemethode zur Behandlung von ADHS? Ein Überblick über aktuelle Befunde
Authors: Drechsler Renate
Published: May 2011

Neurofeedbacktraining hat sich zunehmend als eine klinische Behandlungsmethode für Kinder mit ADHS etabliert, obwohl methodisch befriedigende Wirksamkeitsstudien lange fehlten. Der Überblicksartikel führt zunächst in die Grundlagen von Neurofeedback bei ADHS ein und stellt die wichtigsten Methoden und Protokolle vor. Anschliessend werden aktuelle Studien mit verschiedenen Kontrollbedingungen, Bildgebungsbefunde und Ansätze, die den Zusammenhang zwischen kortikaler Regulation und klinischen Verbesserungen untersuchen, zusammengefasst. Neben vielen offenen methodischen Fragen gibt es auch einige wenige Ergebnisse, die eine spezifische Wirkung von Neurofeedbacktraining stützen. In welchem Ausmass aber die gelernte kortikale Regulation tatsächlich kausal zu den klinischen Verbesserungen beiträgt, müssen zukünftige Untersuchungen noch zeigen.
High‐avidity, high‐IFNγ‐producing CD8 T‐cell responses following immune selection during HIV‐1 infection
Authors: Keane Niamh M , Roberts Steven G , Almeida Coral‐Ann M , Krishnan Tanya , Chopra Abha , Demaine Emma , Laird Rebecca , Tschochner Monika , Carlson Jonathan M , Mallal Simon , Heckerman David , James Ian , John Mina
Published: May 2011

HIV‐1 mutations, which reduce or abolish CTL responses against virus‐infected cells, are frequently selected in acute and chronic HIV infection. Among population HIV‐1 sequences, immune selection is evident as human leukocyte antigen (HLA) allele‐associated substitutions of amino acids within or near CD8 T‐cell epitopes. In these cases, the non‐adapted epitope is susceptible to immune recognition until an escape mutation renders the epitope less immunogenic. However, several population‐based studies have independently identified HLA‐associated viral changes, which lead to the formation of a new T‐cell epitope, suggesting that the immune responses that these variants or ‘neo‐epitopes’ elicit provide an evolutionary advantage to the virus rather than the host. Here, we examined the functional characteristics of eight CD8 T‐cell responses that result from viral adaptation in 125 HLA‐genotyped individuals with chronic HIV‐1 infection. Neo‐epitopes included well‐characterized immunodominant epitopes restricted by common HLA alleles, and in most cases the T‐cell responses against the neo‐epitope showed significantly greater functional avidity and higher IFNγ production than T cells for non‐adapted epitopes, but were not more cytotoxic. Neo‐epitope formation and emergence of cognate T‐cell response coincident with a rise in viral load was then observed in vivo in an acutely infected individual. These findings show that HIV‐1 adaptation not only abrogates the immune recognition of early targeted epitopes, but may also increase immune recognition to other epitopes, which elicit immunodominant but non‐protective T‐cell responses. These data have implications for immunodominance associated with polyvalent vaccines based on the diversity of chronic HIV‐1 sequences.
Kinetics of ocular and systemic antigen‐specific T‐cell responses elicited during murine cytomegalovirus retinitis
Authors: Zinkernagel Martin S , Petitjean Claire , Wikstrom Matthew E , Degli‐Esposti Mariapia A
Published: May 2011

Cytomegalovirus (CMV) reactivation in the retina of immunocompromized patients is a cause of significant morbidity as it can lead to blindness. The adaptive immune response is critical in controlling murine CMV (MCMV) infection in MCMV‐susceptible mouse strains. CD8+ T cells limit systemic viral replication in the acute phase of infection and are essential to contain latent virus. In this study, we provide the first evaluation of the kinetics of anti‐viral T‐cell responses after subretinal infection with MCMV. The acute response was characterized by a rapid expansion phase, with infiltration of CD8+ T cells into the infected retina, followed by a contraction phase. MCMV‐specific T cells displayed biphasic kinetics with a first peak at day 12 and contraction by day 18 followed by sustained recruitment of these cells into the retina at later time points post‐infection. MCMV‐specific CD8+ T cells were also observed in the draining cervical lymph nodes and the spleen. Presentation of viral epitopes and activation of CD8+ T cells was widespread and could be detected in the spleen and the draining lymph nodes, but not in the retina or iris. Moreover, after intraocular infection, antigen‐specific cytotoxic activity was detectable and exhibited kinetics equivalent to those observed after intraperitoneal infection with the same viral dose. These data provide novel insights of how and where immune responses are initiated when viral antigen is present in the subretinal space.
Evaluation of an electrostatic dust removal system with potential application in next-step fusion devices
Authors: Friesen F. Q. L. , John B. , Skinner C. H. , Roquemore A. L. , Calle C. I.
Published: May 2011

The ability to manage inventories of carbon, tritium, and high-Z elements in fusion plasmas depends on means for effective dust removal. A dust conveyor, based on a moving electrostatic potential well, was tested with particles of tungsten, carbon, glass, and sand. A digital microscope imaged a representative portion of the conveyor, and dust particle size and volume distributions were derived before and after operation. About 10 mm3 volume of carbon and tungsten particles were moved in under 5 s. The highest driving amplitude tested of 3 kV was the most effective. The optimal driving frequency was 210 Hz (maximum tested) for tungsten particles, decreasing to below 60 Hz for the larger sand particles. Measurements of particle size and volume distributions after 10 and 100 cycles show the breaking apart of agglomerated carbon and the change in particle distribution over short timescales (<1 s).
Conception of a passive and durable house in Tlemcen (North Africa)
Authors: Boukli Hacene M. A. , Chabane Sari N. E. , Amara S.
Published: May 2011

Our country must face a foreseeable shortage of fossil energies and the consequences of their carefree use. Since the consumption of energy is increasing from every year, we are obliged to develop innovating techniques to bring at least partial solutions to the double problems of the use of the resources and fight against pollution. The sector of housing carries a considerable share of the responsibilities in this matter. The objective of a passive house is to privilege thermal comfort while contributing to energy saving. Our vision of “ecological construction” is centred on the concept of “durability of the environment,” i.e., the adoption of a lifestyle which makes it possible to preserve, to maintain, and to improve quality of the resources and natural balances, and thus to spare the future. The goal of our project is to carry out the following concept that allows to: minimize the energy needs calorific of the building while providing a good quality air inside; utilize renewable energy for the energy needs of the house; control the impacts of a building on the external environment; create an healthy and comfortable environment for its users; preserve the natural resources by optimizing their use, and; promote with sustainable development.
Experimental and numerical analysis of the temperature distribution of injection molded products using protruding microprobes
Authors: Liu Shih-Jung , Ho Chia-Wei
Published: May 2011

Injection molding has been one of the most important polymer processing methods for manufacturing plastic parts. In the process, the temperature is an important parameter that influences process features such as cycle times, crystallization rates, degree of crystallinity, melt flow properties, and molded product qualities. This study aims to, experimentally and numerically, examine the three-dimensional temperature distribution along the melt flow path of injection molded parts. A special experimental set-up, which includes an injection mold equipped with protruding microprobes for guiding embedded thermocouples, was designed and built to measure the temperature field along the flow path, i.e., inside the runner and the cavity, of injection molded products. The experimental results suggested that the disturbance induced by the probes remained negligible and precise temperature profiles could be measured at various positions inside the cavity. A significant increase of melt temperature was found to result from the viscous dissipation of the polymeric materials in the runner. Additionally, a commercially available code was employed to simulate and predict the temperature variation in injection molded parts. It was shown that the numerical simulation predicted better the temperature distributions inside the cavity than those along the runner.
Exploring global changes in nitrogen and phosphorus cycles in agriculture induced by livestock production over the 1900–2050 period
Authors: Bouwman Lex , Goldewijk Kees Klein , Van Der Hoek Klaas W. , Beusen Arthur H. W. , Van Vuuren Detlef P. , Willems Jaap , Rufino Mariana C. , Stehfest Elke
Published: May 2011

Crop-livestock production systems are the largest cause of human alteration of the global nitrogen (N) and phosphorus (P) cycles. Our comprehensive spatially explicit inventory of N and P budgets in livestock and crop production systems shows that in the beginning of the 20th century, nutrient budgets were either balanced or surpluses were small; between 1900 and 1950, global soil N surplus almost doubled to 36 trillion grams (Tg)·y−1and P surplus increased by a factor of 8 to 2 Tg·y−1. Between 1950 and 2000, the global surplus increased to 138 Tg·y−1of N and 11 Tg·y−1of P. Most surplus N is an environmental loss; surplus P is lost by runoff or accumulates as residual soil P. The International Assessment of Agricultural Knowledge, Science, and Technology for Development scenario portrays a world with a further increasing global crop (+82% for 2000–2050) and livestock production (+115%); despite rapidly increasing recovery in crop (+35% N recovery and +6% P recovery) and livestock (+35% N and P recovery) production, global nutrient surpluses continue to increase (+23% N and +54% P), and in this period, surpluses also increase in Africa (+49% N and +236% P) and Latin America (+75% N and +120% P). Alternative management of livestock production systems shows that combinations of intensification, better integration of animal manure in crop production, and matching N and P supply to livestock requirements can effectively reduce nutrient flows. A shift in human diets, with poultry or pork replacing beef, can reduce nutrient flows in countries with intensive ruminant production.
Role of design complexity in technology improvement
Authors: McNerney James , Farmer J. Doyne , Redner Sidney , Trancik Jessika E.
Published: May 2011

We study a simple model for the evolution of the cost (or more generally the performance) of a technology or production process. The technology can be decomposed into
n
components, each of which interacts with a cluster of
d
 - 1 other components. Innovation occurs through a series of trial-and-error events, each of which consists of randomly changing the cost of each component in a cluster, and accepting the changes only if the total cost of the cluster is lowered. We show that the relationship between the cost of the whole technology and the number of innovation attempts is asymptotically a power law, matching the functional form often observed for empirical data. The exponent α of the power law depends on the intrinsic difficulty of finding better components, and on what we term the design complexity: the more complex the design, the slower the rate of improvement. Letting
d
as defined above be the connectivity, in the special case in which the connectivity is constant, the design complexity is simply the connectivity. When the connectivity varies, bottlenecks can arise in which a few components limit progress. In this case the design complexity depends on the details of the design. The number of bottlenecks also determines whether progress is steady, or whether there are periods of stasis punctuated by occasional large changes. Our model connects the engineering properties of a design to historical studies of technology improvement.
Impacts of a recent storm surge on an Arctic delta ecosystem examined in the context of the last millennium
Authors: Pisaric Michael F. J. , Thienpont Joshua R. , Kokelj Steven V. , Nesbitt Holly , Lantz Trevor C. , Solomon Steven , Smol John P.
Published: May 2011

One of the most ominous predictions related to recent climatic warming is that low-lying coastal environments will be inundated by higher sea levels. The threat is especially acute in polar regions because reductions in extent and duration of sea ice cover increase the risk of storm surge occurrence. The Mackenzie Delta of northwest Canada is an ecologically significant ecosystem adapted to freshwater flooding during spring breakup. Marine storm surges during the open-water season, which move saltwater into the delta, can have major impacts on terrestrial and aquatic systems. We examined growth rings of alder shrubs (
Alnus viridis
subsp.
fruticosa
) and diatoms preserved in dated lake sediment cores to show that a recent marine storm surge in 1999 caused widespread ecological changes across a broad extent of the outer Mackenzie Delta. For example, diatom assemblages record a striking shift from freshwater to brackish species following the inundation event. What is of particular significance is that the magnitude of this recent ecological impact is unmatched over the > 1,000-year history of this lake ecosystem. We infer that no biological recovery has occurred in this lake, while large areas of terrestrial vegetation remain dramatically altered over a decade later, suggesting that these systems may be on a new ecological trajectory. As climate continues to warm and sea ice declines, similar changes will likely be repeated in other coastal areas of the circumpolar Arctic. Given the magnitude of ecological changes recorded in this study, such impacts may prove to be long lasting or possibly irreversible.
Discontinuous shear thickening in confined dilute carbon nanotube suspensions
Authors: Majumdar Sayantan , Krishnaswamy Rema , Sood A. K.
Published: May 2011

A monotonic decrease in viscosity with increasing shear stress is a known rheological response to shear flow in complex fluids in general and for flocculated suspensions in particular. Here we demonstrate a discontinuous shear-thickening transition on varying shear stress where the viscosity jumps sharply by four to six orders of magnitude in flocculated suspensions of multiwalled carbon nanotubes (MWNT) at very low weight fractions (approximately 0.5%). Rheooptical observations reveal the shear-thickened state as a percolated structure of MWNT flocs spanning the system size. We present a dynamic phase diagram of the non-Brownian MWNT dispersions revealing a starting jammed state followed by shear-thinning and shear-thickened states. The present study further suggests that the shear-thickened state obtained as a function of shear stress is likely to be a generic feature of fractal clusters under flow, albeit under confinement. An understanding of the shear-thickening phenomena in confined geometries is pertinent for flow-controlled fabrication techniques in enhancing the mechanical strength and transport properties of thin films and wires of nanostructured composites as well as in lubrication issues.
Minimally invasive molecular delivery into the brain using optical modulation of vascular permeability
Authors: Choi Myunghwan , Ku Taeyun , Chong Kyuha , Yoon Jonghee , Choi Chulhee
Published: May 2011

Systemic delivery of bioactive molecules in the CNS is hampered by the blood–brain barrier, which has bottlenecked noninvasive physiological study of the brain and the development of CNS drugs. Here we report that irradiation with an ultrashort pulsed laser to the blood vessel wall induces transient leakage of blood plasma without compromising vascular integrity. By combining this method with a systemic injection, we delivered target molecules in various tissues, including the brain cortex. This tool allows minimally invasive local delivery of chemical probes, nanoparticles, and viral vectors into the brain cortex. Furthermore, we demonstrated astrocyte-mediated vasodilation in vivo without opening the skull, using this method to load a calcium indicator in conjunction with label-free photoactivation of astrocytes.
Regulation of type 17 helper T-cell function by nitric oxide during inflammation
Authors: Niedbala Wanda , Alves-Filho Jose C. , Fukada Sandra Y. , Vieira Silvio Manfredo , Mitani Akio , Sonego Fabiane , Mirchandani Ananda , Nascimento Daniele C. , Cunha Fernando Q. , Liew Foo Y.
Published: May 2011

Type 17 helper T (Th17) cells are implicated in the pathogenesis many of human autoimmune diseases. Development of Th17 can be enhanced by the activation of aryl hydrocarbon receptor (AHR) whose ligands include the environmental pollutant dioxin, potentially linking environmental factors to the increased prevalence of autoimmune disease. We report here that nitric oxide (NO) can suppress the proliferation and function of polarized murine and human Th17 cells. NO also inhibits AHR expression in Th17 cells and the downstream events of AHR activation, including IL-22, IL-23 receptor, and Cyp1a1. Conversely, NO did not affect the polarization of Th17 cells from mice deficient in AHR. Furthermore, mice lacking inducible nitric oxide synthase (Nos2−/−) developed more severe experimental autoimmune encephalomyelitis than WT mice, with elevated AHR expression, increased IL-17A, and IL-22 synthesis. NO may therefore represent an important endogenous regulator to prevent overexpansion of Th17 cells and control of autoimmune diseases caused by environmental pollutants.
Targeted mini-strokes produce changes in interhemispheric sensory signal processing that are indicative of disinhibition within minutes
Authors: Mohajerani Majid H. , Aminoltejari Khatereh , Murphy Timothy H.
Published: May 2011

Most processing of sensation involves the cortical hemisphere opposite (contralateral) to the stimulated limb. Stroke patients can exhibit changes in the interhemispheric balance of sensory signal processing. It is unclear whether these changes are the result of poststroke rewiring and experience, or whether they could result from the immediate effect of circuit loss. We evaluated the effect of mini-strokes over short timescales (<2 h) where cortical rewiring is unlikely by monitoring sensory-evoked activity throughout much of both cortical hemispheres using voltage-sensitive dye imaging. Blockade of a single pial arteriole within the C57BL6J mouse forelimb somatosensory cortex reduced the response evoked by stimulation of the limb contralateral to the stroke. However, after stroke, the ipsilateral (uncrossed) forelimb response within the unaffected hemisphere was spared and became independent of the contralateral forelimb cortex. Within the unaffected hemisphere, mini-strokes in the opposite hemisphere significantly enhanced sensory responses produced by stimulation of either contralateral or ipsilateral pathways within 30–50 min of stroke onset. Stroke-induced enhancement of responses within the spared hemisphere was not reproduced by inhibition of either cortex or thalamus using pharmacological agents in nonischemic animals. I/LnJ acallosal mice showed similar rapid interhemispheric redistribution of sensory processing after stroke, suggesting that subcortical connections and not transcallosal projections were mediating the novel activation patterns. Thalamic inactivation before stroke prevented the bilateral rearrangement of sensory responses. These findings suggest that acute stroke, and not merely loss of activity, activates unique pathways that can rapidly redistribute function within the spared cortical hemisphere.
Agonist trapped in ATP-binding sites of the P2X2 receptor
Authors: Jiang Ruotian , Lemoine Damien , Martz Adeline , Taly Antoine , Gonin Sophie , Prado de Carvalho Lia , Specht Alexandre , Grutter Thomas
Published: May 2011

ATP-gated P2X receptors are trimeric ion channels, as recently confirmed by X-ray crystallography. However, the structure was solved without ATP and even though extracellular intersubunit cavities surrounded by conserved amino acid residues previously shown to be important for ATP function were proposed to house ATP, the localization of the ATP sites remains elusive. Here we localize the ATP-binding sites by creating, through a proximity-dependent “tethering” reaction, covalent bonds between a synthesized ATP-derived thiol-reactive P2X2 agonist (NCS-ATP) and single cysteine mutants engineered in the putative binding cavities of the P2X2 receptor. By combining whole-cell and single-channel recordings, we report that NCS-ATP covalently and specifically labels two previously unidentified positions N140 and L186 from two adjacent subunits separated by about 18 Å in a P2X2 closed state homology model, suggesting the existence of at least two binding modes. Tethering reaction at both positions primes subsequent agonist binding, yet with distinct functional consequences. Labeling of one position impedes subsequent ATP function, which results in inefficient gating, whereas tethering of the other position, although failing to produce gating by itself, enhances subsequent ATP function. Our results thus define a large and dynamic intersubunit ATP-binding pocket and suggest that receptors trapped in covalently agonist-bound states differ in their ability to gate the ion channel.
HIV DNA is heavily uracilated, which protects it from autointegration
Authors: Yan Nan , O'Day Elizabeth , Wheeler Lee Adam , Engelman Alan , Lieberman Judy
Published: May 2011

Human immune cells infected by HIV naturally contain high uracil content, and HIV reverse transcriptase (RT) does not distinguish between dUTP and dTTP. Many DNA viruses and retroviruses encode a dUTPase or uracil-DNA glycosylase (UNG) to counteract uracil incorporation. However, although HIV virions are thought to contain cellular UNG2, replication of HIV produced in cells lacking UNG activity does not appear to be impaired. Here we show that HIV reverse transcripts generated in primary human immune cells are heavily uracilated (>500 uracils per 10 kb HIV genome). We find that HIV DNA uracilation, rather than being dangerous, may promote the early phase of the viral life cycle. Shortly after reverse transcription, the ends of the HIV DNA are activated by the viral integrase (IN) in preparation for chromosomal insertion. However, the activated ends can attack the viral DNA itself in a suicidal side pathway, called autointegration. We find here that uracilation of target DNA inhibits the strand transfer of HIV DNA ends by IN, thereby inhibiting autointegration and facilitating chromosomal integration and viral replication. When uracilation is increased by incubating uracil-poor cells in the presence of increasing concentrations of dUTP or by infecting with virus that contains the cytosine deaminase APOBEC3G (A3G), the proportion of reverse transcripts that undergo suicidal autointegration decreases. Thus, HIV tolerates, or even benefits from, nonmutagenic uracil incorporation during reverse transcription in human immune cells.
Genetic modulation of horizontal cell number in the mouse retina
Authors: Whitney Irene E. , Raven Mary A. , Ciobanu Daniel C. , Poché Ross A. , Ding Qian , Elshatory Yasser , Gan Lin , Williams Robert W. , Reese Benjamin E.
Published: May 2011

Neuronal populations display conspicuous variability in their size among individuals, but the genetic sources of this variation are largely undefined. We demonstrate a large and highly heritable variation in neuron number within the mouse retina, affecting a critical population of interneurons, the horizontal cells. Variation in the size of this population maps to the distal end of chromosome (Chr) 13, a region homologous to human Chr 5q11.1–11.2. This region contains two genes known to modulate retinal cell number. Using conditional knock-out mice, we demonstrate that one of these genes, the LIM homeodomain geneIslet-1(Isl1), plays a role in regulating horizontal cell number. Genetic differences inIsl1expression are high during the period of horizontal cell production, andcis-regulation ofIsl1expression within the retina is demonstrated directly. We identify a single nucleotide polymorphism in the 5′ UTR ofIsl1that creates an E-box sequence as a candidate causal variant contributing to this variation in horizontal cell number.
Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine
Authors: Boltz Valerie F. , Zheng Yu , Lockman Shahin , Hong Feiyu , Halvas Elias K. , McIntyre James , Currier Judith S. , Chibowa Margret C. , Kanyama Cecelia , Nair Apsara , Owino-Ong'or Willis , Hughes Michael , Coffin John M. , Mellors John W.
Published: May 2011

In the OCTANE/A5208 study of initial antiretroviral therapy (ART) in women exposed to single-dose nevirapine (sdNVP) ≥6 mo earlier, the primary endpoint (virological failure or death) was significantly more frequent in the NVP-containing treatment arm than in the lopinavir/ritonavir-containing treatment arm. Detection of NVP resistance in plasma virus at study entry by standard population genotype was strongly associated with the primary endpoint in the NVP arm, but two-thirds of endpoints occurred in women without NVP resistance. We hypothesized that low-frequency NVP-resistant mutants, missed by population genotype, explained excess failure in the NVP treatment arm. Plasma samples from 232 participants were analyzed by allele-specific PCR at study entry to quantify NVP-resistant mutants down to 0.1% for 103N and 190A and to 0.3% for 181C. Of 201 women without NVP resistance by population genotype, 70 (35%) had NVP-resistant mutants detected by allele-specific PCR. Among these 70 women, primary endpoints occurred in 12 (32%) of 38 women in the NVP arm vs. 3 (9%) of 32 in the lopinavir/ritonavir-containing arm (hazard ratio = 3.84). The occurrence of a primary endpoint in the NVP arm was significantly associated with the presence of K103N or Y181C NVP-resistant mutations at frequencies >1%. The risk for a study endpoint associated with NVP-resistant mutant levels did not decrease with time. Therefore, among women with prior exposure to sdNVP, low-frequency NVP-resistant mutants were associated with increased risk for failure of NVP-containing ART. The implications for choosing initial ART for sdNVP-exposed women are discussed.
A TRPA1-dependent mechanism for the pungent sensation of weak acids
Authors: Wang Yuanyuan Y. , Chang Rui B. , Allgood Sallie D. , Silver Wayne L. , Liman Emily R.
Published: May 2011

Acetic acid produces an irritating sensation that can be attributed to activation of nociceptors within the trigeminal ganglion that innervate the nasal or oral cavities. These sensory neurons sense a diverse array of noxious agents in the environment, allowing animals to actively avoid tissue damage. Although receptor mechanisms have been identified for many noxious chemicals, the mechanisms by which animals detect weak acids, such as acetic acid, are less well understood. Weak acids are only partially dissociated at neutral pH and, as such, some can cross the cell membrane, acidifying the cell cytosol. The nociceptor ion channel TRPA1 is activated by CO2, through gating of the channel by intracellular protons, making it a candidate to more generally mediate sensory responses to weak acids. To test this possibility, we measured responses to weak acids from heterologously expressed TRPA1 channels and trigeminal neurons with patch clamp recording and Ca2+ microfluorometry. Our results show that heterologously expressed TRPA1 currents can be induced by a series of weak organic acids, including acetic, propionic, formic, and lactic acid, but not by strong acids. Notably, the degree of channel activation was predicted by the degree of intracellular acidification produced by each acid, suggesting that intracellular protons are the proximate stimulus that gates the channel. Responses to weak acids produced a Ca2+-independent inactivation that precluded further activation by weak acids or reactive chemicals, whereas preactivation by reactive electrophiles sensitized TRPA1 channels to weak acids. Importantly, responses of trigeminal neurons to weak acids were highly overrepresented in the subpopulation of TRPA1-expressing neurons and were severely reduced in neurons from TRPA1 knockout mice. We conclude that TRPA1 is a general sensor for weak acids that produce intracellular acidification and suggest that it functions within the pain pathway to mediate sensitivity to cellular acidosis.
Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume
Authors: Geng Yanyan , Niu Xiaowei , Magleby Karl L.
Published: May 2011

Large-conductance Ca2+- and voltage-activated K+ (BK) channels have the largest conductance (250–300 pS) of all K+-selective channels. Yet, the contributions of the various parts of the ion conduction pathway to the conductance are not known. Here, we examine the contribution of the entrance to the inner cavity to the large conductance. Residues at E321/E324 on each of the four α subunits encircle the entrance to the inner cavity. To determine if 321/324 is accessible from the inner conduction pathway, we measured single-channel current amplitudes before and after exposure and wash of thiol reagents to the intracellular side of E321C and E324C channels. MPA− increased currents and MTSET+ decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. For neutral amino acids, decreasing the size of the entrance to the inner cavity by substituting large side-chain amino acids at 321/324 decreased outward single-channel conductance, whereas increasing the size of the entrance with smaller side-chain substitutions had little effect. Reductions in outward conductance were negated by high [K+]i. Substitutions had little effect on inward conductance. Fitting plots of conductance versus side-chain volume with a model consisting of one variable and one fixed resistor in series indicated an effective diameter and length of the entrance to the inner cavity for wild-type channels of 17.7 and 5.6 Å, respectively, with the resistance of the entrance ∼7% of the total resistance of the conduction pathway. The estimated dimensions are consistent with the structure of MthK, an archaeal homologue to BK channels. Our observations suggest that BK channels have a low resistance, large entrance to the inner cavity, with the entrance being as large as necessary to not limit current, but not much larger.
Probe measurements of electron-energy distributions in plasmas: what can we measure and how can we achieve reliable results?
Authors: Godyak V A , Demidov V I
Published: May 2011

An electric-probe method for the diagnostics of electron-distribution functions (EDFs) in plasmas is reviewed with emphasis on receiving reliable results while taking into account appropriate probe construction, various measurement errors and the limitations of theories. The starting point is a discussion of the Druyvesteyn method for measurements in weakly ionized, low-pressure and isotropic plasma. This section includes a description of correct probe design, the influence of circuit resistance, ion current and plasma oscillations and probe-surface effects on measurements. At present, the Druyvesteyn method is the most developed, consistent and routine way to measure the EDF. The following section of the review describes an extension of the classical EDF measurements into higher pressures, magnetic fields and anisotropic plasmas. To date, these methods have been used by a very limited number of researchers. Therefore, their verification has not yet been fully completed, and their reliable implementation still requires additional research. Nevertheless, the described methods are complemented by appropriate examples of measurements demonstrating their potential value.