bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the central renin-angiotensin system in Parkinson’s disease
Authors: Mertens Birgit , Vanderheyden Patrick , Michotte Yvette , Sarre Sophie
Published: October 2009

Since the discovery of a renin-angiotensin system (RAS) in the brain, several studies have linked this central RAS to neurological disorders such as ischaemia, Alzheimer’s disease and depression. In the last decade, evidence has accumulated that the central RAS might also play a role in Parkinson’s disease. Although the exact cause of this progressive neurodegenerative disorder of the basal ganglia remains unidentified, inflammation and oxidative stress have been suggested to be key factors in the pathogenesis and the progression of the disease. Since angiotensin II is a pro-inflammatory compound that can induce the production of reactive oxygen species due to activation of the NADPH-dependent oxidase complex, this peptide might contribute to dopaminergic cell death. In this review, three different strategies to interfere with the pathogenesis or the progression of Parkinson’s disease are discussed. They include inhibition of the angiotensin-converting enzyme, blockade of the angiotensin II type 1 receptor and stimulation of the angiotensin II type 2 receptor.
The angiotensin II type 2 receptor in the brain
Authors: Horiuchi Masatsugu , Mogi Masaki , Iwai Masaru
Published: October 2009

Recent clinical studies indicate that blockade of the renin-angiotensin system is important to prevent stroke, and accumulating results of basic research also indicate the possible involvement of the central renin-angiotensin system in ischaemic brain damage and cognition. When the angiotensin II type 1 receptor is blocked by an angiotensin type 1 receptor blocker, unbound angiotensin II acts preferentially on the angiotensin II type 2 (AT2) receptor. These results suggest the pathophysiological importance of the AT2receptor in the clinical use of angiotensin type 1 receptor blockers, which are widely used in patients with hypertension with the expectation of a decrease in the onset of cardiovascular and cerebrovascular disease. We review here the possible roles of AT2receptor activation in the brain, focusing on ischaemic stroke, cognitive function and neurogenesis, and potential effects of specific AT2receptor agonists.
Type 2 diabetic patients with resistant hypertension should be screened for primary aldosteronism
Authors: Mukherjee J.J. , Khoo C.M. , Thai A.C. , Chionh S.B. , Pin Lim , Lee K.O.
Published: October 2009

BP control in diabetic patients is often poor. The contribution of secondary hypertension due to undiagnosed PA in hypertensive type 2 diabetic patients is not well studied. We prospectively screened 100 consecutive Asian type 2 diabetic patients with difficult-to-control or resistant hypertension for PA. PAC (pmol/L) to PRA (ng/mL/h) ratio was measured; those with PAC-to-PRA ratio >550 (corresponding PAC >415) underwent intravenous 0.9% SLT. Patients with PAC ≥140 following SLT had CT adrenals and bilateral AVS. Thirteen patients (13%) were confirmed to have PA, and all had resistant hypertension. Eight had a surgically correctable form of PA. Patients with PA had higher mean (SD) systolic [159.0 (10.6) vs. 146.0 (10.7) mmHg, p=0.001] and diastolic BP [94.6 (6.0) vs. 87.6 (5.9) mmHg, p=0.001], lower serum potassium [3.5 (0.6) vs. 4.3 (0.5) mmol/L, p=0.001], and higher PAC [679.3 (291.0) vs. 239.5 (169.4) pmol/L, p=0.001]. Identification and institution of definitive treatment for PA resulted in better BP control and in a reduction in the use of antihypertensive medications. Our findings demonstrate a high prevalence of PA in type 2 diabetic patients with resistant hypertension. Systematic screening for PA in this select group is recommended, as targeted treatment improves BP control.
Relaunching a National Social Marketing Campaign
Authors: Faulkner Guy , McCloy Cora , Plotnikoff Ronald C. , Tremblay Mark S.
Published: October 2009

ParticipACTION is a Canadian physical activity communications and social marketing organization that has been relaunched in 2007 after a 6-year hiatus. The purpose of this study is to qualitatively identify and describe the expectations and challenges the relaunch of the new ParticipACTION may present for existing physical activity organizations. Using a purposeful sampling strategy, the authors conduct semistructured telephone interviews with 49 key informants representing a range of national, provincial, and local organizations with a mandate to promote physical activity. Overall, there is strong support in seeing ParticipACTION relaunched. However, organizational expectations and/or their ideal vision for it are mixed. Organizations envision and support its performing an overarching social marketing and advocacy role, and in providing tools and resources that supplement existing organizational activities. Four major organizational challenges are identified concerning overlapping mandates, partnership and leadership concerns, competition for funding, and capacity concerns. Social marketing initiatives, such as ParticipACTION, may not be able to maximize their impact unless they address the expectations and concerns of competing organizations with a mandate to promote physical activity.
Human Siglec-10 can bind to vascular adhesion protein-1 and serves as its substrate
Authors: Kivi Elina , Elima Kati , Aalto Kristiina , Nymalm Yvonne , Auvinen Kaisa , Koivunen Erkki , Otto Diana M. , Crocker Paul R. , Salminen Tiina A. , Salmi Marko , Jalkanen Sirpa
Published: October 2009

Leukocytes migrate from the blood into areas of inflammation by interacting with various adhesion molecules on endothelial cells. Vascular adhesion protein-1 (VAP-1) is a glycoprotein expressed on inflamed endothelium where it plays a dual role: it is both an enzyme that oxidizes primary amines and an adhesin that is involved in leukocyte trafficking to sites of inflammation. Although VAP-1 was identified more than 15 years ago, the counterreceptor(s) for VAP-1 on leukocytes has remained unknown. Here we have identified Siglec-10 as a leukocyte ligand for VAP-1 using phage display screenings. The binding between Siglec-10 and VAP-1 was verified by different adhesion assays, and this interaction was also consistent with molecular modeling. Moreover, the interaction between Siglec-10 and VAP-1 led to increased hydrogen peroxide production, indicating that Siglec-10 serves as a substrate for VAP-1. Thus, the Siglec-10–VAP-1 interaction seems to mediate lymphocyte adhesion to endothelium and has the potential to modify the inflammatory microenvironment via the enzymatic end products.
Alpha-defensins secreted by dysplastic granulocytes inhibit the differentiation of monocytes in chronic myelomonocytic leukemia
Authors: Droin Nathalie , Jacquel Arnaud , Hendra Jean-Baptiste , Racoeur Cindy , Truntzer Caroline , Pecqueur Delphine , Benikhlef Naïma , Ciudad Marion , Guery Leslie , Jooste Valérie , Dufour Erick , Fenaux Pierre , Quesnel Bruno , Kosmider Olivier , Fontenay Michaëla , Ducoroy Patrick , Solary Eric
Published: October 2009

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder that occurs in elderly patients. One of the main diagnostic criteria is the accumulation of heterogeneous monocytes in the peripheral blood. We further explored this cellular heterogeneity and observed that part of the leukemic clone in the peripheral blood was made of immature dysplastic granulocytes with a CD14−/CD24+ phenotype. The proteome profile of these cells is dramatically distinct from that of CD14+/CD24− monocytes from CMML patients or healthy donors. More specifically, CD14−/CD24+ CMML cells synthesize and secrete large amounts of alpha-defensin 1-3 (HNP1-3). Recombinant HNPs inhibit macrophage colony-stimulating factor (M-CSF)–driven differentiation of human peripheral blood monocytes into macrophages. Using transwell, antibody-mediated depletion, suramin inhibition of purinergic receptors, and competitive experiments with uridine diphosphate (UDP)/uridine triphosphate (UTP), we demonstrate that HNP1-3 secreted by CD14−/CD24+ cells inhibit M-CSF–induced differentiation of CD14+/CD24− cells at least in part through P2Y6, a receptor involved in macrophage differentiation. Altogether, these observations suggest that a population of immature dysplastic granulocytes contributes to the CMML phenotype through production of alpha-defensins HNP1-3 that suppress the differentiation capabilities of monocytes.
How I treat multiple myeloma in younger patients
Authors: Stewart A. Keith , Richardson Paul G. , San-Miguel Jesus F.
Published: October 2009

Therapeutic options for multiple myeloma (MM) patients have changed quickly in recent years and uncertainty has arisen about optimal approaches to therapy. A reasonable goal of MM treatment in younger “transplant eligible” patients is to initiate therapy with a target goal of durable complete remission, and the anticipated consequence of long-term disease control. To achieve this goal we recommend induction therapy with multi-agent combination chemotherapies (usually selected from bortezomib, lenalidomide, thalidomide, cyclophosphamide, and corticosteriods) which when employed together elicit frequent, rapid, and deep responses. We recommend consolidation with high-dose melphalan and autologous stem cell transplantation in the majority of patients willing and able to undergo this procedure and subsequent maintenance therapy, especially in those failing to achieve a complete response or at high risk for early relapse based on prognostic, genetically defined risk factors. Defining genetic risk for early relapse is therefore an important aspect of early diagnostic testing and attention to minimizing expected toxicities once therapy begins is critical in ensuring the efficacy of modern combination therapy approaches. When access to newer drugs is restricted participation in clinical trials should be pursued.
Progranulin is expressed within motor neurons and promotes neuronal cell survival
Authors: Ryan Cara L , Baranowski David C , Chitramuthu Babykumari P , Malik Suneil , Li Zhi , Cao Mingju , Minotti Sandra , Durham Heather D , Kay Denis G , Shaw Christopher A , Bennett Hugh PJ , Bateman Andrew
Published: October 2009

Background

Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival.

Results

In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival.

Conclusion

Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease.
An efficient drug delivery vehicle for botulism countermeasure
Authors: Zhang Peng , Ray Radharaman , Singh Bal Ram , Li Dan , Adler Michael , Ray Prabhati
Published: October 2009

Background

Botulinum neurotoxin (BoNT) is the most potent poison known to mankind. Currently no antidote is available to rescue poisoned synapses. An effective medical countermeasure strategy would require developing a drug that could rescue poisoned neuromuscular synapses and include its efficient delivery specifically to poisoned presynaptic nerve terminals. Here we report a drug delivery strategy that could directly deliver toxin inhibitors into the intoxicated nerve terminal cytosol.

Results

A targeted delivery vehicle was developed for intracellular transport of emerging botulinum neurotoxin antagonists. The drug delivery vehicle consisted of the non-toxic recombinant heavy chain of botulinum neurotoxin-A coupled to a 10-kDa amino dextran via the heterobifunctional linker 3-(2-pyridylthio)-propionyl hydrazide. The heavy chain served to target botulinum neurotoxin-sensitive cells and promote internalization of the complex, while the dextran served as a platform to deliver model therapeutic molecules to the targeted neurons. Our results indicated that the drug delivery vehicle entry into neurons was via BoNT-A receptor mediated endocytosis. Once internalized into neurons, the drug carrier component separated from the drug delivery vehicle in a fashion similar to the separation of the BoNT-A light chain from the holotoxin. This drug delivery vehicle could be used to deliver BoNT-A antidotes into BoNT-A intoxicated cultured mouse spinal cord cells.

Conclusion

An effective BoNT-based drug delivery vehicle can be used to directly deliver toxin inhibitors into intoxicated nerve terminal cytosol. This approach can potentially be utilized for targeted drug delivery to treat other neuronal and neuromuscular disorders. This report also provides new knowledge of endocytosis and exocytosis as well as of BoNT trafficking.
Remarkable sequence similarity between the dinoflagellate-infecting marine girus and the terrestrial pathogen African swine fever virus
Authors: Ogata Hiroyuki , Toyoda Kensuke , Tomaru Yuji , Nakayama Natsuko , Shirai Yoko , Claverie Jean-Michel , Nagasaki Keizo
Published: October 2009

Heterocapsa circularisquama DNA virus (HcDNAV; previously designated as HcV) is a giant virus (girus) with a ~356-kbp double-stranded DNA (dsDNA) genome. HcDNAV lytically infects the bivalve-killing marine dinoflagellate H. circularisquama, and currently represents the sole DNA virus isolated from dinoflagellates, one of the most abundant protists in marine ecosystems. Its morphological features, genome type, and host range previously suggested that HcDNAV might be a member of the family Phycodnaviridae of Nucleo-Cytoplasmic Large DNA Viruses (NCLDVs), though no supporting sequence data was available. NCLDVs currently include two families found in aquatic environments (Phycodnaviridae, Mimiviridae), one mostly infecting terrestrial animals (Poxviridae), another isolated from fish, amphibians and insects (Iridoviridae), and the last one (Asfarviridae) exclusively represented by the animal pathogen African swine fever virus (ASFV), the agent of a fatal hemorrhagic disease in domestic swine. In this study, we determined the complete sequence of the type B DNA polymerase (PolB) gene of HcDNAV. The viral PolB was transcribed at least from 6 h post inoculation (hpi), suggesting its crucial function for viral replication. Most unexpectedly, the HcDNAV PolB sequence was found to be closely related to the PolB sequence of ASFV. In addition, the amino acid sequence of HcDNAV PolB showed a rare amino acid substitution within a motif containing highly conserved motif: YS DTDS was found in HcDNAV PolB instead of YG DTDS in most dsDNA viruses. Together with the previous observation of ASFV-like sequences in the Sorcerer II Global Ocean Sampling metagenomic datasets, our results further reinforce the ideas that the terrestrial ASFV has its evolutionary origin in marine environments.
γ-Aminobutyric Acid and Glutamate Differentially Regulate Intracellular Calcium Concentrations in Mouse Gonadotropin-Releasing Hormone Neurons
Authors: Constantin Stephanie , Jasoni Christine L. , Wadas Brandon , Herbison Allan E.
Published: October 2009

Multiple factors regulate the activity of the GnRH neurons responsible for controlling fertility. Foremost among neuronal inputs to GnRH neurons are those using the amino acids glutamate and γ-aminobutyric acid (GABA). The present study used a GnRH-Pericam transgenic mouse line, enabling live cell imaging of intracellular calcium concentrations ([Ca2+]i) to evaluate the effects of glutamate and GABA signaling on [Ca2+]i in peripubertal and adult mouse GnRH neurons. Activation of GABAA, N-methyl-d-aspartate, or α-amino-3-hydroxyl-5-methyl-4-isoxazole propionate acid (AMPA) receptors was found to evoke an increase in [Ca2+]i, in subpopulations of GnRH neurons. Approximately 70% of GnRH neurons responded to GABA, regardless of postnatal age or sex. Many fewer (∼20%) GnRH neurons responded to N-methyl-d-aspartate, and this was not influenced by postnatal age or sex. In contrast, about 65% of adult male and female GnRH neurons responded to AMPA compared with about 14% of male and female peripubertal mice (P < 0.05). The mechanisms underlying the ability of GABA and AMPA to increase [Ca2+]i in adult GnRH neurons were evaluated pharmacologically. Both GABA and AMPA were found to evoke [Ca2+]i increases through a calcium-induced calcium release mechanism involving internal calcium stores and inositol-1,4,5-trisphosphate receptors. For GABA, the initial increase in [Ca2+]i originated from GABAA receptor-mediated activation of L-type voltage-gated calcium channels, whereas for AMPA this appeared to involve direct calcium entry through the AMPA receptor. These observations show that all of the principal amino acid receptors are able to control [Ca2+]i in GnRH neurons but that they do so in a postnatal age- and intracellular pathway-specific manner.
“Whether Beast or Human”: The Cultural Legacies of Dread, Locks, and Dystopia
Authors: Frank Kevin
Published: October 2009

Analyzing the ongoing problem of Caribbean racial exploitation, particularly fear signified through one of the most potent Caribbean symbols, dreadlocks, I argue that Medusa's alterity is altered by Rastafarians' snake-like hair, but the transformative power of Rasta dreadlocks is contested through certain cinematic depictions of dread.
King Menelik's Nephew: Prince Thomas Mackarooroo, aka Prince Ludwig Menelek of Abyssinia
Authors: Hill Robert A.
Published: October 2009

Although little studied or understood, the black impostor occupies an important place in the history of the African diaspora. The present essay examines the imposture of Prince Thomas Mackarooroo, aka Prince Ludwig Menelek of Abyssinia, as an avatar of Emperor Menelik II of Ethiopia, whose military victory over Italian forces at the Battle of Adwa in 1896 made him the black culture hero par excellence at the height of the imperialist era. The black impostor, it is argued, represents a political actor of a certain type.
Distinct roles for Crk adaptor isoforms in actin reorganization induced by extracellular signals
Authors: Antoku Susumu , Mayer Bruce J.
Published: October 2009

Crk family adaptors, consisting of Src homology 2 (SH2) and SH3 protein-binding domains, mediate assembly of protein complexes in signaling. CrkI, an alternately spliced form of Crk, lacks the regulatory phosphorylation site and C-terminal SH3 domain present in CrkII and CrkL. We used gene silencing combined with mutational analysis to probe the role of Crk adaptors in platelet-derived growth-factor receptor β (PDGFβR) signaling. We demonstrate that Crk adaptors are required for formation of focal adhesions, and for PDGF-stimulated remodeling of the actin cytoskeleton and cell migration. Crk-dependent signaling is crucial during the early stages of PDGFβR activation, whereas its termination by Abl family tyrosine kinases is important for turnover of focal adhesions and progression of dorsal-membrane ruffles. CrkII and CrkL preferentially activate the small GTPase Rac1, whereas variants lacking a functional C-terminal SH3 domain, including CrkI, preferentially activate Rap1. Thus, differences in the activity of Crk isoforms, including their effectors and their ability to be downregulated by phosphorylation, are important for coordinating dynamic changes in the actin cytoskeleton in response to extracellular signals.
Downregulation of thymosin β4 in neural progenitor grafts promotes spinal cord regeneration
Authors: Mollinari Cristiana , Ricci-Vitiani Lucia , Pieri Massimo , Lucantoni Corrado , Rinaldi Anna Maria , Racaniello Mauro , De Maria Ruggero , Zona Cristina , Pallini Roberto , Merlo Daniela , Garaci Enrico
Published: October 2009

Thymosin β4 (Tβ4) is an actin-binding peptide whose expression in developing brain correlates with migration and neurite extension of neurons. Here, we studied the effects of the downregulation of Tβ4 expression on growth and differentiation of murine neural progenitor cells (NPCs), using an antisense lentiviral vector. In differentiation-promoting medium, we found twice the number of neurons derived from the Tβ4-antisense-transduced NPCs, which showed enhanced neurite outgrowth accompanied by increased expression of the adhesion complex N-cadherin–β-catenin and increased ERK activation. Importantly, when the Tβ4-antisense-transduced NPCs were transplanted in vivo into a mouse model of spinal cord injury, they promoted a significantly greater functional recovery. Locomotory recovery correlated with increased expression of the regeneration-promoting cell adhesion molecule L1 by the grafted Tβ4-antisense-transduced NPCs. This resulted in an increased number of regenerating axons and in sprouting of serotonergic fibers surrounding and contacting the Tβ4-antisense-transduced NPCs grafted into the lesion site. In conclusion, our data identify a new role for Tβ4 in neuronal differentiation of NPCs by regulating fate determination and process outgrowth. Moreover, NPCs with reduced Tβ4 levels generate an L1-enriched environment in the lesioned spinal cord that favors growth and sprouting of spared host axons and enhances the endogenous tissue-repair processes.
Chatter prevention and improved finish of workpiece for a milling process
Authors: Tsai N-C , Chen D-C , Lee R-M
Published: October 2009

This paper presents how real-time chatter prevention can be realized by feedback of an acoustic cutting signal. The efficacy of the proposed adaptive spindle speed tuning algorithm is verified by intensive experimental simulations. A pair of microphones, perpendicular to each other, is used to acquire the acoustic cutting signal resulting from milling chatter. A real-time feedback control loop is constructed for spindle speed compensation in such a way to ensure that the milling process is within the stability zone of the stability lobe diagram.

The acoustic chatter signal index (ACSI) and the spindle speed compensation strategy (SSCS) are proposed to quantify the acoustic signal and actively to tune the spindle speed respectively. By converting the acoustic feedback signal into the ACSI, an appropriate spindle speed compensation rate (SSCR) can be determined by the SSCS based on a real-time chatter level or the ACSI. Accordingly, the compensation command, referred to as added-on voltage (AOV), is applied to increase/decrease the spindle motor speed. By employing the commercial software MATLAB/Simulink and the dSpace DS1104 interface module to implement the controller, the proposed chatter prevention algorithm is practically verified by intensive experiments. By inspection on the precision and quality of the workpiece surface after milling, the efficacy of the real-time chatter prevention strategy via acoustic signal feedback is further assured.
Improved slicing algorithm employing nearest distance method
Authors: Vatani M , Barazandeh F , Rahimi A R , Sanati Nezhad A
Published: October 2009

Although stereo lithography (STL) file format is widely used as a de facto industry standard in rapid prototyping (RP), there are in practice always some defects and shortcomings when the slicing output file (SOF) is generated. As the model size and complexity grow, the defects grow exponentially and as a result it becomes impossible to fix the STL files manually. Modifying the head-to-tail algorithm, a new method that produces an error-free SOF (in spite of defects in the original STL file) with fewer data to analyse is presented herein. The nearest distance algorithm employed guarantees fully closed contours.
Wear mechanisms of TiN-coated CBN tool during finish hard turning of hot tool die steel
Authors: Dureja J S , Gupta V K , Sharma V S , Dogra M
Published: October 2009

The aim of the present investigation was to identify the wear mechanisms of TiN-coated CBN tools prevalent under different machining conditions during hard turning of hot tool die steel. The different wear mechanisms observed were abrasion wear at low cutting speed, low feed rate, and high workpiece hardness; formation of a transferred layer resulting from tribochemical reactions between constituents of the tool and workpiece material at high speed; and the formation of built-up edges at moderate cutting speed. Hard carbide particles of the work material at higher feed rate severely abraded the tool flank land, resulting in shallow grooves due to the detachment of CBN grains. At greater depth of cut, the built-up edges and transferred layer reduced friction and tool wear. Excessive adhesion of workpiece material followed by plastic deformation and notching were clearly visible at low workpiece hardness (47 HRC). The influence of cutting speed, feed rate, depth of cut, and workpiece hardness on the progressive tool flank wear, i.e. flank wear rate (VBr, μm/mm) in the steady wear region, was also analysed. The flank wear rate was observed to decrease with increase in cutting speed, depth of cut, and workpiece hardness, but after an initial decrease it increased with increase in feed rate.
From multi-body to many-body dynamics
Authors: Theodossiades S , Teodorescu M , Rahnejat H
Published: October 2009

This article provides a brief historical review of multi-body dynamics analysis, initiated by the Newtonian axioms through constrained ( removed degrees of freedom) Lagrangian dynamics or restrained ( resisted degrees of freedom) Newton—Euler formulation. It provides a generic formulation method, based on system dynamics in a reduced configuration space, which encompasses both the aforementioned methods and is applicable to any cluster of material points. A detailed example is provided to show the integration of other physical phenomena such as flexibility and acoustic wave propagation into multi-body dynamics analysis.

It is shown that in the scale of minutiae, when the action potentials deviate from Newtonian laws, the forces are often described by empirical or stochastic functions of separation and the medium of interactions. These make for complex analyses and distinguish a host of many body problems from Newtonian laws of motion. A simple example is provided to demonstrate this. It is suggested that unification of many-body analysis with that of multi-body dynamics is incumbent on the fundamental understanding of interaction potentials at close separations.
Non-undercutting region and property evaluation of epitrochoidal gerotor geometry
Authors: Hsieh C-F
Published: October 2009

The gerotor pump is widely used for industrial applications. In this paper, the inner rotor profile is an equidistant epitrochoidal curve, and the outer rotor is generated by the inner rotor profile. This paper discusses an undercutting analysis of the rotor profile, in which the undercutting equations are derived by the theory of gearing. The non-undercutting region is determined by the undercutting curves of the inner and the outer rotors. Numerical examples show that the non-undercutting region on the gerotor profiles only needs to consider the lower part of the undercutting curve of the inner rotor. Besides, the curvature equations of the outer and inner rotors are derived for evaluating the rotor profile properties such as assessing the sealing property and the Hertz stress forecast. The theoretical stress and software simulations proved the stress forecast. The results obtained are important for using the gerotor profile in optimum design.
A completely meshless analysis of cracks in isotropic functionally graded materials
Authors: Koohkan H , Baradaran G H , Vaghefi R
Published: October 2009

In the present study, a completely meshless analysis of two-dimensional cracks in non-homogeneous, isotropic, and linear elastic functionally graded materials (FGMs) is developed. The meshless local Petrov—Galerkin method is applied and the equilibrium equations are considered to drive the local symmetric weak formulations. The moving least-squares approximation is used to interpolate the solution variables and the penalty method is applied to impose the essential boundary conditions. Also, a new technique for defining local sub-domain and support domain is proposed. Using the technique, more nodes are considered in the direction of material variation and extra nodes are located near the crack tip of the FGM body to obtain an accurate meshless model. The based functions are also enriched in order to capture singularities around the crack tip. Several numerical examples containing both mode-I and mixed-mode conditions are presented and the results are compared with the available solutions in the literature which shows a good agreement.
An analytical model to predict bending angles in high-frequency induction heat forming
Authors: Chen J , Qi Y , Shi Y , Bi Z
Published: October 2009

In induction heat forming, the deformation field of the metal plate is dependent on the temperature field. In the investigations on the temperature field, by defining a dimensionless temperature and a special Y-coordinate, it can be found that temperature distributions in the Y′-direction are similar for different thicknesses. To predict the bending deformation, an analytical model of temperature distribution is derived based on the similarity of temperatures at different thicknesses. An analytical model of the bending angle under the temperature gradient mechanism in the straight-line induction heat forming is obtained using the above temperature model. The proposed model is parametric and considers the dimensions of the plate and the laser process parameters. To verify the proposed model, the bending angles calculated by the analytical model are compared with those measured experimentally. The analytical results of the bending angle generally show good agreement with the experimental results. This investigation will be helpful for determining the heating conditions required for producing complex shapes of the plate.
Absolute quantification of microRNAs by using a universal reference
Authors: Bissels Ute , Wild Stefan , Tomiuk Stefan , Holste Angela , Hafner Markus , Tuschl Thomas , Bosio Andreas
Published: October 2009

MicroRNAs (miRNAs) are a species of small RNAs ∼21–23-nucleotides long that have been shown to play an important role in many different cellular, developmental, and physiological processes. Accordingly, numerous PCR-, sequencing-, or hybridization-based methods have been established to identify and quantify miRNAs. Their short length results in a high dynamic range of melting temperatures and therefore impedes a proper selection of detection probes or optimized PCR primers. While miRNA microarrays allow for massive parallel and accurate relative measurement of all known miRNAs, they have so far been less useful as an assay for absolute quantification. Here, we present a microarray-based approach for global and absolute quantification of miRNAs. The method relies on the parallel hybridization of the sample of interest labeled with Cy5 and a universal reference of 954 synthetic miRNAs in equimolar concentrations that are labeled with Cy3 on a microarray slide containing probes for all human, mouse, rat, and viral miRNAs (miRBase 12.0). Each single miRNA is quantified with respect to the universal reference canceling biases related to sequence, labeling, or hybridization. We demonstrate the accuracy of the method by various spike-in experiments. Furthermore, we quantified miRNA copy numbers in liver samples and CD34(+)/CD133(−) hematopoietic progenitor cells.
Dynamic Lead-Time Quotation for an M/M/1 Base-Stock Inventory Queue
Authors: Savaşaneril Seçil , Griffin Paul M. , Keskinocak Pınar
Published: October 2009

We study a dynamic lead-time quotation problem in a base-stock inventory system characterized by lead-time sensitive Poisson demand and exponentially distributed service times. We show that the optimal profit is unimodal in the base-stock level. We compare the base-stock system with a make-to-order (MTO) system and show that the lead-time quotes are lower in an MTO system and that increasing the base-stock level does not necessarily decrease the expected number of customers waiting. Numerical results show that when customers are less sensitive to lead-time quotes, the benefit of quoting lead times with a higher precision is significant, whereas when customers are more sensitive to lead-time quotes, the benefit of holding inventory is significant.
Impaired osteoblast function in GPRC6A null mice
Authors: Pi Min , Zhang Lishu , Lei Shu-Feng , Huang Min-Zhao , Zhu Wenyu , Zhang Jianghong , Shen Hui , Deng Hong-Wen , Quarles L Darryl
Published: October 2009

GPRC6A is a widely expressed orphan G protein–coupled receptor that senses extracellular amino acids, osteocalcin, and divalent cations in vitro. GPRC6A null (GPRC6A−/−) mice exhibit multiple metabolic abnormalities including osteopenia. To investigate whether the osseous abnormalities are a direct function of GPRC6A in osteoblasts, we examined the function of primary osteoblasts and bone marrow stromal cell cultures (BMSCs) in GPRC6A−/− mice. We confirmed that GPRC6A−/− mice exhibited a decrease in bone mineral density (BMD) associated with reduced expression of osteocalcin, ALP, osteoprotegerin, and Runx2-II transcripts in bone. Osteoblasts and BMSCs derived from GPRC6A−/− mice exhibited an attenuated response to extracellular calcium-stimulated extracellular signal-related kinase (ERK) activation, diminished alkaline phosphatase (ALP) expression, and impaired mineralization ex vivo. In addition, siRNA-mediated knockdown of GPRC6A in MC3T3 osteoblasts also resulted in a reduction in extracellular calcium-stimulated ERK activity. To explore the potential relevance of GPRC6A function in humans, we looked for an association between GPRC6A gene polymorphisms and BMD in a sample of 1000 unrelated American Caucasians. We found that GPRC6A gene polymorphisms were significantly associated with human spine BMD. These data indicate that GRPC6A directly participates in the regulation of osteoblast-mediated bone mineralization and may mediate the anabolic effects of extracellular amino acids, osteocalcin, and divalent cations in bone. © 2010 American Society for Bone and Mineral Research
The Effect of Core and Carburized Surface Microstructural Stability on Residual Stress Evolution during Tempering
Authors: Vatavuk Jan , di Monte Mariana Zicari , Couto Antonio Augusto
Published: October 2009

It is a well-known fact that compressive residual stresses are developed during the quenching process of carburized parts. The main purpose of this work is related to the tempering effects on as-quenched compressive residual stresses of commercial carburized samples. The work was carried out by using SAE 4120 RH steel samples with different diameters (15 and 38 mm), which led to different cooling rates with a direct effect on the nucleus microstructure. The carburized surface microstructure was considered similar. The 15 mm bars nucleus microstructures were predominantly martensitic but bainitic in the larger samples. The as-quenched surface compressive residual stress was lower in the smaller diameter samples. The compressive residual stress reduction due to increasing tempering temperature was continuous for the larger diameter work piece. The smaller diameter samples had different behaviors in two regions; the compressive stress for lower tempering temperatures was reduced, while values were enhanced over higher temperatures.
Chapter 2: Measuring Techniques
Authors: Guo Dan , Luo Jiangbin , Hu Yuanzhong
Published: October 2009

THE DEVELOPMENT OFNEWTECHNIQUES TO MEAsure surface topography, adhesion, friction, wear, lubricant film thickness, and mechanical properties on a micro- and nanometre scale has led to a new field referred to as micro/nanotribology, which is concerned with experimental and theoretical investigation of processes occurring from micro scales down to atomic or molecular scales. Such studies are becoming ever more important as moving parts and mating surfaces continue to be smaller. Micro/nanotribological studies are crucial to develop a fundamental understanding of interfacial phenomena occurring at such small scales and are boosted by the various industrial requirements. The first apparatus for nanotribology research is the Surface Force Apparatus (SFA) invented by Tabor and Winterton [1] in 1969, which is used to study the static and dynamic performance of lubricant film between two molecule-smooth interactions. The invention of the Scanning Tunneling Microscopy (STM) in 1981 by Binning and Rohrer [2] at the IBM Zurich Research Laboratory suddenly revolutionized the field of surface science and was awarded the Nobel Prize in 1986. This was the first instrument capable of directly obtaining three-dimensional images of a solid surface with atomic resolution and paved the way for a whole new family of Scanning Probe Microscopies (SPM), e.g., Atomic Force Microscopy (AFM), Friction Force Microscopy (FFM), and others. The AFM and FFM are widely used in nanotribological and nanomechanics studies for measuring surface topography and roughness, friction, adhesion, elasticity, scratch resistance, and for nanolithography and nanomachine.
Physics and Chemistry of Micro-Nanotribology
Authors: Wen Shizhu , Luo Jianbin , Hu Yuanzhong
Published: October 2009

Description

This new ASTM monograph presents the principles and applications of tribology in micro- nano-scale and discusses some of the challenges faced by tribilogists since the development of new manufacturing techniques for electronic products. It covers a broad range of topics on micro-nanotribology, with emphasis on the physical and chemical aspects and on bridging fundamental studies and applications.

Topics include:

This is a valuable resource for tribologists, mechanical engineers, lubrication engineers, and material scientist and engineers.
Structural Changes between Seasons in the Songbird Auditory Forebrain
Authors: De Groof Geert , Verhoye Marleen , Poirier Colline , Leemans Alexander , Eens Marcel , Darras Veerle M. , Van der Linden Annemie
Published: October 2009

The song control system (SCS) of seasonal songbirds shows remarkable seasonal plasticity. Male starlings (Sturnus vulgaris) sing throughout the year, but in the breeding season, when concentrations of testosterone are elevated, the song is highly sexually motivated. The main goal of this study was to investigate structural seasonal changes in regions involved in auditory processing and in socio-sexual behavior. Usingin vivoDiffusion Tensor Imaging (DTI), we measured in breeding and nonbreeding seasons volume and tissue characteristics of several brain regions of nine adult male starlings. We demonstrate that the songbird brain exhibits an extreme seasonal plasticity not merely limited to the SCS. Volumetric analysis showed seasonal telencephalon volume changes and more importantly also a volumetric change in the caudal region of the nidopallium (NCM), a region analogous to the mammalian secondary auditory cortex. Analysis of the DTI data allowed detection of seasonal changes in cellular attributes in NCM and regions involved in social behavior. This study extends our view on a seasonally dynamic avian brain which not only hones its song control system but also auditory and social systems to be prepared for the breeding season.
Control of On/Off Glomerular Signaling by a Local GABAergic Microcircuit in the Olfactory Bulb
Authors: Gire David H. , Schoppa Nathan E.
Published: October 2009

Odors are coded at the input level of the olfactory bulb by a spatial map of activated glomeruli, reflecting different odorant receptors (ORs) stimulated in the nose. Here we examined the function of local synaptic processing within glomeruli in transforming these input patterns into an output for the bulb, using patch-clamp recordings and calcium imaging in rat bulb slices. Two types of transformations were observed at glomeruli, the first of which produced a bimodal, “on/off” glomerular signal that varied probabilistically depending on olfactory receptor neuron (ORN) input levels. The bimodal response behavior was seen in glomerular synaptic responses, as well as in action potential (“spike”) firing, wherein all mitral cells affiliated with a glomerulus either engaged in prolonged spike bursts or did not spike at all. In addition, evidence was obtained that GABAergic periglomerular (PG) cells that surround a glomerulus can prevent activation of a glomerulus through inhibitory inputs targeted onto excitatory external tufted cells. The path of PG cell activation appeared to be confined to one glomerulus, such that ORNs at one glomerulus initiated inhibition of the same glomerulus. The observed glomerular “self-inhibition” provides a mechanism of filtering odor signals that would be an alternative to commonly proposed mechanisms of lateral inhibition between OR-specific glomeruli. In this case, selective suppression of weak odor signals could be achieved based on the difference in the input resistance of PG cells versus excitatory neurons at a glomerulus.
Pattern Motion Selectivity of Spiking Outputs and Local Field Potentials in Macaque Visual Cortex
Authors: Khawaja Farhan A. , Tsui James M. G. , Pack Christopher C.
Published: October 2009

The dorsal pathway of the primate visual cortex is involved in the processing of motion signals that are useful for perception and behavior. Along this pathway, motion information is first measured by the primary visual cortex (V1), which sends specialized projections to extrastriate regions such as the middle temporal area (MT). Previous work with plaid stimuli has shown that most V1 neurons respond to the individual components of moving stimuli, whereas some MT neurons are capable of estimating the global motion of the pattern. In this work, we show that the majority of neurons in the medial superior temporal area (MST), which receives input from MT, have this pattern-selective property. Interestingly, the local field potentials (LFPs) measured simultaneously with the spikes often exhibit properties similar to that of the presumptive feedforward input to each area: in the high-gamma frequency band, the LFPs in MST are as component selective as the spiking outputs of MT, and MT LFPs have plaid responses that are similar to the spiking outputs of V1. In the lower LFP frequency bands (beta and low gamma), component selectivity is very common, and pattern selectivity is almost entirely absent in both MT and MST. Together, these results suggest a surprisingly strong link between the sensory tuning of cortical LFPs and afferent inputs, with important implications for the interpretation of imaging studies and for models of cortical function.
Identification of Two Distinct Macrophage Subsets with Divergent Effects Causing either Neurotoxicity or Regeneration in the Injured Mouse Spinal Cord
Authors: Kigerl Kristina A. , Gensel John C. , Ankeny Daniel P. , Alexander Jessica K. , Donnelly Dustin J. , Popovich Phillip G.
Published: October 2009

Macrophages dominate sites of CNS injury in which they promote both injury and repair. These divergent effects may be caused by distinct macrophage subsets, i.e., “classically activated” proinflammatory (M1) or “alternatively activated” anti-inflammatory (M2) cells. Here, we show that an M1 macrophage response is rapidly induced and then maintained at sites of traumatic spinal cord injury and that this response overwhelms a comparatively smaller and transient M2 macrophage response. The high M1/M2 macrophage ratio has significant implications for CNS repair. Indeed, we present novel data showing that only M1 macrophages are neurotoxic and M2 macrophages promote a regenerative growth response in adult sensory axons, even in the context of inhibitory substrates that dominate sites of CNS injury (e.g., proteoglycans and myelin). Together, these data suggest that polarizing the differentiation of resident microglia and infiltrating blood monocytes toward an M2 or “alternatively” activated macrophage phenotype could promote CNS repair while limiting secondary inflammatory-mediated injury.
Selective Expression of a Sodium Pump Isozyme by Cough Receptors and Evidence for Its Essential Role in Regulating Cough
Authors: Mazzone Stuart B. , Reynolds Sandra M. , Mori Nanako , Kollarik Marian , Farmer David G. , Myers Allen C. , Canning Brendan J.
Published: October 2009

We have identified a distinct subtype of airway vagal afferent nerve that plays an essential role in regulating the cough reflex. These afferents are exquisitely sensitive to punctate mechanical stimuli, acid, and decreases in extracellular chloride concentrations, but are insensitive to capsaicin, bradykinin, histamine, adenosine, serotonin, or changes in airway intraluminal pressures. In this study we used intravital imaging, retrograde neuronal tracing, and electrophysiological analyses to characterize the structural basis for their peculiar mechanical sensitivity and to further characterize the regulation of their excitability. In completing these experiments, we uncovered evidence for an essential role of an isozyme of Na+-K+ATPase in regulating cough. These vagal sensory neurons arise bilaterally from the nodose ganglia and are selectively and brilliantly stained intravitally with the styryl dye FM2-10. Cough receptor terminations are confined and adherent to the extracellular matrix separating the airway epithelium and smooth muscle layers, a site of extensive remodeling in asthma and chronic obstructive pulmonary disease. The cough receptor terminals uniquely express the α3subunit of Na+-K+ATPase. Intravital staining of cough receptors by FM2-10, cough receptor excitabilityin vitro, and coughingin vivoare potently and selectively inhibited by the sodium pump inhibitor ouabain. These data provide the first detailed morphological description of the peripheral terminals of the sensory nerves regulating cough and identify a selective molecular target for their modulation.