bluuebunny/crossref_metadata_2025 huggingface dataset:
Harpocratism
Authors: Mulsow Martin
Published: December 2009

When authors act by either publishing or non-publishing their texts, they sometimes use a language of gestures. These gestures can assist to position the author in the intellectual field. In this way some German eighteenth-century philosophers who thought against the grain of mainstream rationalism withdrew from the public sphere, using the image of the Egyptian god Harpocrates, who puts his index finger to his lips—a symbol for maintaining silence. In a sense one can thus label this kind of quietism as “harpocratism.” The essay examines the imagery and contextualizes it in three case studies from the years 1720-50. Moreover, it explores its sources in political as well as antiquarian and hermetic discourses of the sixteenth and seventeenth centuries. The essay serves as a model for defining intellectual positions not so much by their content, but rather by their practices of symbolic distancing from others, of building identities in emotional communities, and of shaping free zones of inquiry where they could flourish.
Resource Allocation Policies for Personalization in Content Delivery Sites
Authors: Liu Dengpan , Sarkar Sumit , Sriskandarajah Chelliah
Published: December 2009

One of the distinctive features of sites on the Internet is their ability to gather enormous amounts of information about their visitors and to use this information to enhance a visitor's experience by providing personalized information or recommendations. In providing personalized services, a website is typically faced with the following trade-off: When serving a visitor's request, it can deliver an optimally personalized version of the content to the visitor, possibly with a long delay because of the computational effort needed, or it can deliver a suboptimal version of the content more quickly. This problem becomes more complex when several requests are waiting for information from a server. The website then needs to trade off the benefit from providing more personalized content to each user with the negative externalities associated with higher waiting costs for all other visitors that have requests pending. We examine several deterministic resource allocation policies in such personalization contexts. We identify an optimal policy for the above problem when requests to be scheduled are batched, and show that the policy can be very efficiently implemented in practice. We provide an experimental approach to determine optimal batch lengths, and demonstrate that it performs favorably when compared with viable queueing approaches.
Information Technology and Firm Boundaries: Impact on Firm Risk and Return Performance
Authors: Dewan Sanjeev , Ren Fei
Published: December 2009

In this paper, we empirically investigate the impact of information technology (IT) investment on firm return and risk financial performance, emphasizing the moderating role of the firm boundary strategies of diversification and vertical integration. Our results indicate a sharp contrast between the direct and interactive effects of IT on both the return (profitability) and risk (variability of returns) dimensions. Although the direct effect of IT capital is to increase firm risk for a given level of return, we find that suitable boundary strategies can moderate the impact of IT on firm performance in a way that increases return and decreases risk, at the margin. This interaction effect is strongest in service firms, in firms with high levels of IT investment intensity, and in more recent time periods. Our results are robust to alternative proxies for firm risk, including an ex ante risk measure (variability of analysts' earnings estimates), and alternative risk-return specifications. Put together, our results provide new insights into how IT and firm boundary strategies interact to affect the risk and return performance of firms.
OR Practice—Catch-Up Scheduling for Childhood Vaccination
Authors: Engineer Faramroze G. , Keskinocak Pınar , Pickering Larry K.
Published: December 2009

In this paper, we outline the development of the core optimization technology used within a decision support tool to help providers and caretakers in constructing catch-up schedules for childhood immunization. These schedules ensure that a child continues to receive timely coverage against vaccine-preventable diseases in the likely event that one or more doses have been delayed.

This project was undertaken as part of a collaborative effort between the Centers for Disease Control and Prevention (CDC) and Georgia Institute of Technology. Our aim is to develop a decision support tool that removes from the task of constructing catch-up schedules the tedious combinatorial aspects, while maintaining a level of generality that allows easy accommodation for changes in the existing rules and adding new vaccines to the schedule lineup.

We show that the catch-up scheduling problem is NP-hard, and we develop a dynamic programming algorithm that exploits the typical size and structure of the problem to construct optimized schedules almost at the click of a button. In using an optimization-based algorithm, our approach is unique not only in methodology but also in the information, strategy, and advice we can offer to the user.

The tool is being advocated by both the CDC and the American Academy of Pediatrics (AAP) as a means of encouraging caretakers and providers to take a more proactive role in ensuring timely vaccination coverage for children, as well as ensuring the accuracy and quality of a catch-up regime.
A Clinical Review of Echinocandins in Pediatric Patients
Authors: VandenBussche Heather L , Van Loo Dean A
Published: December 2009

OBJECTIVE

To identify and evaluate available data on pediatric echinocandin use.

DATA SOURCES

A PubMed search, limited to English-language articles, was conducted (1990-August 2009) using the search terms echinocandin, pediatric, child, pharmacokinetics, caspofungin, micafungin, and anidulafungin. Additional articles were retrieved from citations of selected references.

STUDY SELECTION AND DATA EXTRACTION

Relevant information on the pharmacology, pharmacokinetics, efficacy, and safety of echinocandins in children was selected. Clinical trials, retrospective reviews, and case series were identified and evaluated. Data from these sources were included in this review.

DATA SYNTHESIS

Caspofungin is the only echinocandin approved by the Food and Drug Administration for use in children. Pediatric pharmacokinetics has been evaluated with all 3 echinocandins but is limited with anidulafungin. Micafungin is the most well-studied agent in prospective clinical trials for antifungal prophylaxis in stem cell transplantation and treatment of invasive fungal infections. Caspofungin has been studied prospectively for febrile neutropenia and treatment of invasive fungal infections, but most published data are from retrospective reviews or case reports. One case report of anidulafungin for neonatal candidiasis has been published. The role of echinocandins in the management of invasive pediatric fungal infections has expanded. Micafungin and caspofungin are recommended as primary or alternative treatment of candidemia and esophageal or invasive candidiasis, and as salvage therapy for invasive aspergillosis. Micafungin is recommended for neutropenic prophylaxis in stem cell transplantation, while caspofungin may be used in febrile neutropenia as an alternative to azoles. Dosing has been well established for caspofungin only in children 3 months of age and above. Anidulafungin should be avoided in children until more pharmacokinetic and clinical data become available.

CONCLUSIONS

Further comparative trials are needed to more clearly define the role of echinocandins, either as monotherapy or in combination for difficult-to-treat infections, in the pediatric population.
Plerixafor for Stem Cell Mobilization in Patients with Non-Hodgkin's Lymphoma and Multiple Myeloma
Authors: Choi Hye-Yoon , Yong Chul-Soon , Yoo Bong Kyu
Published: December 2009

OBJECTIVE

To evaluate the literature characterizing the mechanism of action, pharmacokinetics, pharmacodynamics, and therapeutic efficacy of plerixafor for hematopoietic stem cell (HSC) mobilization for autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) or multiple myeloma.

DATA SOURCES

A PubMed search (1966-September 2009) was conducted using the key words plerixafor and AMD3100. Manufacturer's prescribing information was also used.

STUDY SELECTION AND DATA EXTRACTION

English-language articles were selected and data were extracted with a focus on clinical studies of HSC mobilization in patients with NHL or multiple myeloma.

DATA SYNTHESIS

Plerixafor exerts its effect by reversibly blocking the ability of HSC to bind to the bone marrow matrix. When used with granulocyte colony-stimulating factor (G-CSF), plerixafor helps increase the number of HSCs in the peripheral blood, where they can be collected for use in autologous transplantation. In clinical studies, plerixafor was rapidly absorbed after subcutaneous injection, reaching a maximum plasma concentration at approximately 0.5 hours. Plerixafor is renally excreted as the parent drug, with an elimination half-life ranging from 3 to 5 hours. Plerixafor increases circulating CD34+ cells in the peripheral blood, with a peak effect about 6–9 hours after subcutaneous administration. An approximate 2- to 3-fold increase in the CD34+ cell count is seen by the first dose of plerixafor after 4 consecutive days of G-CSF treatment. In 2 Phase 3 studies in patients with NHL or multiple myeloma, addition of plerixafor to G-CSF resulted in a higher CD34+ cell collection with fewer apheresis days, but failed to show better graft durability or overall patient survival for up to 12 months of follow-up.

CONCLUSIONS

Clinical trials have demonstrated that the addition of plerixafor to G-CSF was beneficial for HSC mobilization to peripheral blood for collection and subsequent transplantation in patients with NHL or multiple myeloma. Further studies should assess the benefit of the additive use of plerixafor on clinical outcomes.
Towards a pedagogy for teaching adaptations
Authors: Raw Laurence
Published: December 2009

This article looks at how I have interpreted the notion of adaptation studies in my teaching practice at a private university in Ankara, Turkey. I begin by outlining the educational context in which I work, focusing on how the top-down model of education dominates local teaching practice.
This is chiefly due to a desire to remain true to the principles of Islam and secularism propounded by Mustafa Kemal Atatrk, the founder of the Turkish Republic. I subsequently suggest that this approach to education overlooks recent socio-political changes in the country, particularly a move
towards more pluralistic models of identity. In the final section, I show how I have tried to reinterpret the concept of adaptation, as understood in the Turkish context, to reformulate an approach to pedagogy within the ELT context (but which could also be applied to other subjects), that
encourages individual responses and develops more creative approaches to teaching texts.
ALCAM Regulates Mediolateral Retinotopic Mapping in the Superior Colliculus
Authors: Buhusi Mona , Demyanenko Galina P. , Jannie Karry M. , Dalal Jasbir , Darnell Eli P. B. , Weiner Joshua A. , Maness Patricia F.
Published: December 2009

ALCAM [activated leukocyte cell adhesion molecule (BEN/SC-1/DM-GRASP)] is a transmembrane recognition molecule of the Ig superfamily (IgSF) containing five Ig domains (two V-type, three C2-type). Although broadly expressed in the nervous and immune systems, few of its developmental functions have been elucidated. Because ALCAM has been suggested to interact with the IgSF adhesion molecule L1, a determinant of retinocollicular mapping, we hypothesized that ALCAM might direct topographic targeting to the superior colliculus (SC) by serving as a substrate within the SC for L1 on incoming retinal ganglion cell (RGC) axons. ALCAM was expressed in the SC during RGC axon targeting and on RGC axons as they formed the optic nerve; however, it was downregulated distally on RGC axons as they entered the SC. Axon tracing with DiI revealed pronounced mistargeting of RGC axons from the temporal retina half of ALCAM null mice to abnormally lateral sites in the contralateral SC, in which these axons formed multiple ectopic termination zones. ALCAM null mutant axons were specifically compromised in medial orientation of interstitial branches, which is known to require the ankyrin binding function of L1. As a substrate, ALCAM–Fc protein promoted L1-dependent attachment of acutely dissociated retinal cells and an L1-expressing, ALCAM-negative cell line, consistent with an ALCAM–L1 heterophilic molecular interaction. Together, these results suggest a model in which ALCAM in the SC interacts with L1 on RGC axons to promote medial extension of RGC axon branches important for mediolateral axon targeting in the formation of retinocollicular maps.
Age- and Gender-Related Differences in the Cortical Anatomical Network
Authors: Gong Gaolang , Rosa-Neto Pedro , Carbonell Felix , Chen Zhang J. , He Yong , Evans Alan C.
Published: December 2009

Neuroanatomical differences attributable to aging and gender have been well documented, and these differences may be associated with differences in behaviors and cognitive performance. However, little is known about the dynamic organization of anatomical connectivity within the cerebral cortex, which may underlie population differences in brain function. In this study, we investigated age and sex effects on the anatomical connectivity patterns of 95 normal subjects ranging in age from 19 to 85 years. Using the connectivity probability derived from diffusion magnetic resonance imaging tractography, we characterized the cerebral cortex as a weighted network of connected regions. This approach captures the underlying organization of anatomical connectivity for each subject at a regional level. Advanced graph theoretical analysis revealed that the resulting cortical networks exhibited “small-world” character (i.e., efficient information transfer both at local and global scale). In particular, the precuneus and posterior cingulate gyrus were consistently observed as centrally connected regions, independent of age and sex. Additional analysis revealed a reduction in overall cortical connectivity with age. There were also changes in the underlying network organization that resulted in decreased local efficiency, and also a shift of regional efficiency from the parietal and occipital to frontal and temporal neocortex in older brains. In addition, women showed greater overall cortical connectivity and the underlying organization of their cortical networks was more efficient, both locally and globally. There were also distributed regional differences in efficiency between sexes. Our results provide new insights into the substrates that underlie behavioral and cognitive differences in aging and sex.
Emx1-Lineage Progenitors Differentially Contribute to Neural Diversity in the Striatum and Amygdala
Authors: Cocas Laura A. , Miyoshi Goichi , Carney Rosalind S. E. , Sousa Vitor H. , Hirata Tsutomu , Jones Kevin R. , Fishell Gord , Huntsman Molly M. , Corbin Joshua G.
Published: December 2009

In the developing mammalian basal telencephalon, neural progenitors from the subpallium generate the majority of inhibitory medium spiny neurons (MSNs) in the striatum, while both pallial- and subpallial-derived progenitors contribute to excitatory and inhibitory neuronal diversity in the amygdala. Using a combination of approaches, including genetic fate mapping, cell birth dating, cell migration assays, and electrophysiology, we find that cells derived from theEmx1lineage contribute to two distinct neuronal populations in the mature basal forebrain: inhibitory MSNs in the striatum and functionally distinct subclasses of excitatory neurons in the amygdala. Our cell birth-dating studies reveal that these two populations are born at different times during early neurogenesis, with the amygdala population born before the MSNs. In the striatum,Emx1-lineage neurons represent a unique subpopulation of MSNs: they are disproportionately localized to the dorsal striatum, are found in dopamine receiving, reelin-positive patches, and are born throughout striatal neurogenesis. In addition, our data suggest that a subpopulation of theseEmx1-lineage cells originate in the pallium and subsequently migrate to the developing striatum and amygdala. Our intersectional fate-mapping analysis further reveals thatEmx1-lineage cells that coexpressDlxexclusively generate MSNs but do not contribute to the excitatory neurons in the amygdala. Thus, both the timing of neurogenesis and differential combinatorial gene expression appear to be key determinants of striatal versus amygdala fate decisions ofEmx1-lineage cells.
Transplanted Neural Precursors Enhance Host Brain-Derived Myelin Regeneration
Authors: Einstein Ofira , Friedman-Levi Yael , Grigoriadis Nikolaos , Ben-Hur Tamir
Published: December 2009

In multiple sclerosis lesions resident oligodendrocyte progenitor cells (OPCs) are present, but fail to remyelinate. In the current study we examined whether neural precursor cell (NPC) transplantation can facilitate host brain-derived remyelination. We used the chronic cuprizone-induced demyelination model in aged mice, in which slow remyelination follows cuprizone removal. NPCs were transplanted to the lateral ventricles (intracerebroventricular) of cuprizone-induced demyelinated brains. In this experimental setup, transplanted cells remained mostly in the periventricular area in an undifferentiated state. The extent of demyelination, remyelination, and proliferation of host brain regenerative cell population were examined at 1 week posttransplantation in the splenium of the corpus callosum, which was devoid of any transplanted cells. Transplantation of NPCs, but not of control, human embryonic kidney cells, significantly enhanced remyelination compared with sham-operated mice. Remyelination was performed exclusively by host brain OPCs. The proregenerative effect of transplanted NPCs was related to an increase in the proliferation of host brain OPCs. To examine the mechanism that underlies the proregenerative effect of NPCsin vitro, we used an NPC–OPC coculture system. These experiments indicated that NPCs induced the proliferation of OPCs and facilitated their differentiation into mature oligodendrocytes. The mitogenic effect of NPCs was mediated by platelet-derived growth factor-AA and fibroblast growth factor-2. In conclusion, NPC transplantation enhances host-derived myelin regeneration following chronic demyelination. This trophic effect may stimulate resident OPCs to overcome the remyelination failure in multiple sclerosis.
Diminutive Digits Discern Delicate Details: Fingertip Size and the Sex Difference in Tactile Spatial Acuity
Authors: Peters Ryan M. , Hackeman Erik , Goldreich Daniel
Published: December 2009

We have observed that passive tactile spatial acuity, the ability to resolve the spatial structure of surfaces pressed upon the skin, differs subtly but consistently between the sexes, with women able to perceive finer surface detail than men. Eschewing complex central explanations, we hypothesized that this sex difference in somatosensory perception might result from simple physical differences between the fingers of women and men. To investigate, we tested 50 women and 50 men on a tactile grating orientation task and measured the surface area of the participants' index fingertips. In subsets of participants, we additionally measured finger skin compliance and optically imaged the fingerprint microstructure to count sweat pores. We show here that tactile perception improves with decreasing finger size, and that this correlation fully explains the better perception of women, who on average have smaller fingers than men. Indeed, when sex and finger size are both considered in statistical analyses, only finger size predicts tactile acuity. Thus, a man and a woman with fingers of equal size will, on average, enjoy equal tactile acuity. We further show that sweat pores, and presumably the Merkel receptors beneath them, are packed more densely in smaller fingers.
Amyloid Precursor Protein Regulates Cav1.2 L-type Calcium Channel Levels and Function to Influence GABAergic Short-Term Plasticity
Authors: Yang Li , Wang Zilai , Wang Baiping , Justice Nicholas J. , Zheng Hui
Published: December 2009

Amyloid precursor protein (APP) has been strongly implicated in the pathogenesis of Alzheimer's disease (AD). Although impaired synaptic function is believed to be an early and causative event in AD, how APP physiologically regulates synaptic properties remains poorly understood. Here, we report a critical role for APP in the regulation of L-type calcium channels (LTCC) in GABAergic inhibitory neurons in striatum and hippocampus.APPdeletion in mice leads to an increase in the levels of Cav1.2, the pore-forming subunit of LTCCs, and subsequent increases in GABAergic calcium currents (ICa2+) that can be reversed by reintroduction of APP. Upregulated levels of Cav1.2 result in reduced GABAergic paired-pulse inhibition and increased GABAergic post-tetanic potentiation in both striatal and hippocampal neurons, indicating that APP modulates synaptic properties of GABAergic neurons by regulating Cav1.2. Furthermore, APP physically interacts with Cav1.2, suggesting a mechanism in which loss of APP leads to an inappropriate accumulation and aberrant activity of Cav1.2. These results provide a direct link between APP and calcium signaling and might help explain how altered APP regulation leads to changes in synaptic function that occur with AD.
Early-Life Stress Disrupts Attachment Learning: The Role of Amygdala Corticosterone, Locus Ceruleus Corticotropin Releasing Hormone, and Olfactory Bulb Norepinephrine
Authors: Moriceau Stephanie , Shionoya Kiseko , Jakubs Katherine , Sullivan Regina M.
Published: December 2009

Infant rats require maternal odor learning to guide pups' proximity-seeking of the mother and nursing. Maternal odor learning occurs using a simple learning circuit including robust olfactory bulb norepinephrine (NE), release from the locus ceruleus (LC), and amygdala suppression by low corticosterone (CORT). Early-life stress increases NE but also CORT, and we questioned whether early-life stress disrupted attachment learning and its neural correlates [2-deoxyglucose (2-DG) autoradiography]. Neonatal rats were normally reared or stressed-reared during the first 6 d of life by providing the mother with insufficient bedding for nest building and were odor–0.5 mA shock conditioned at 7 d old. Normally reared paired pups exhibited typical odor approach learning and associated olfactory bulb enhanced 2-DG uptake. However, stressed-reared pups showed odor avoidance learning and both olfactory bulb and amygdala 2-DG uptake enhancement. Furthermore, stressed-reared pups had elevated CORT levels, and systemic CORT antagonist injection reestablished the age-appropriate odor-preference learning, enhanced olfactory bulb, and attenuated amygdala 2-DG. We also assessed the neural mechanism for stressed-reared pups' abnormal behavior in a more controlled environment by injecting normally reared pups with CORT. This was sufficient to produce odor aversion, as well as dual amygdala and olfactory bulb enhanced 2-DG uptake. Moreover, we assessed a unique cascade of neural events for the aberrant effects of stress rearing: the amygdala–LC–olfactory bulb pathway. Intra-amygdala CORT or intra-LC corticotropin releasing hormone (CRH) infusion supported aversion learning with intra-LC CRH infusion associated with increased olfactory bulb NE (microdialysis). These results suggest that early-life stress disturbs attachment behavior via a unique cascade of events (amygdala–LC–olfactory bulb).
Activity-Dependent Vesicular Monoamine Transporter-Mediated Depletion of the Nucleus Supports Somatic Release by Serotonin Neurons
Authors: Colgan Lesley A. , Putzier Ilva , Levitan Edwin S.
Published: December 2009

Packaging by the vesicular monoamine transporter (VMAT) is essential for mood-controlling serotonin transmission but has not been assayed during activity. Here, two-photon imaging of the fluorescent serotonin analog 5,7-dihydroxytryptamine and three-photon imaging of endogenous serotonin were used to study vesicular packaging as it supports release from the soma of serotonin neurons. Glutamate receptor activation in dorsal raphe brain slice evoked somatic release that was mediated solely by vesicle exocytosis. This release was accompanied by VMAT-mediated serotonin depletion from the nucleus, a large compartment free of monoaminergic degradation pathways that has not been implicated in neurotransmission previously. Finally, while some monoamine packaged at rest was held in reserve, monoamine packaged during stimulation was released completely. Hence, somatic vesicles loaded by VMAT during activity rapidly undergo exocytosis. In the absence of active zones and with limited neurotransmitter reuptake, somatic release by serotonin neurons is supported by recruitment from a large pool of extravesicular serotonin in the nucleus and cytoplasm, and preferential release of the newly packaged transmitter.
Unexpected Lack of Hypersensitivity in LRRK2 Knock-Out Mice to MPTP (1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine)
Authors: Andres-Mateos Eva , Mejias Rebeca , Sasaki Masayuki , Li Xiaojie , Lin Brian M. , Biskup Saskia , Zhang Li , Banerjee Rebecca , Thomas Bobby , Yang Lichuan , Liu Guosheng , Beal M. Flint , Huso David L. , Dawson Ted M. , Dawson Valina L.
Published: December 2009

Mutations in theleucine-rich repeat kinase 2(LRRK2) gene are the most common known cause of Parkinson's disease (PD). Whether loss of LRRK2 function accounts for neurodegeneration of dopamine neurons in PD is not known, nor is it known whether LRRK2 kinase activity modulates the susceptibility of dopamine (DA) neurons to the selective dopaminergic toxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To better understand the role of LRRK2 in DA neuronal survival and its role in the susceptibility of DA neurons to MPTP, we generated LRRK2 knock-out (KO) mice lacking the kinase domain of LRRK2. Here, we show that LRRK2 KO mice are viable and have no major abnormalities and live to adulthood. The dopaminergic system is normal in LRRK2 KO mice as assessed via HPLC for DA and its metabolites and via stereologic assessment of DA neuron number in young and aged mice. Importantly, there is no significant difference in the susceptibility of LRRK2 KO and wild-type mice to MPTP. These results suggest that LRRK2 plays little if any role in the development and survival of DA neurons under physiologic conditions. Thus, PD due to LRRK2 mutations are likely not due to a loss of function. Moreover, LRRK2 is not required for the susceptibility of DA neurons to MPTP.
A Novel Allele of Myosin VIIa Reveals a Critical Function for the C-Terminal FERM Domain for Melanosome Transport in Retinal Pigment Epithelial Cells
Authors: Schwander Martin , Lopes Vanda , Sczaniecka Anna , Gibbs Daniel , Lillo Concepcion , Delano David , Tarantino Lisa M. , Wiltshire Tim , Williams David S. , Müller Ulrich
Published: December 2009

Mutations in the head and tail domains of the motor protein myosin VIIA (MYO7A) cause deaf-blindness (Usher syndrome type 1B, USH1B) and nonsyndromic deafness (DFNB2, DFNA11). The head domain binds to F-actin and serves as the MYO7A motor domain, but little is known about the function of the tail domain. In a genetic screen, we have identifiedpolkamice, which carry a mutation (c.5742 + 5G > A) that affects splicing of the MYO7A transcript and truncates the MYO7A tail domain at the C-terminal FERM domain. In the inner ear, expression of the truncated MYO7A protein is severely reduced, leading to defects in hair cell development. In retinal pigment epithelial (RPE) cells, the truncated MYO7A protein is expressed at comparative levels to wild-type protein but fails to associate with and transport melanosomes. We conclude that the C-terminal FERM domain of MYO7A is critical for melanosome transport in RPE cells. Our findings also suggest thatMYO7Amutations can lead to tissue-specific effects on protein levels, which may explain why some mutations inMYO7Alead to deafness without retinal impairment.
Netrin-1-Dependent Spinal Interneuron Subtypes Are Required for the Formation of Left-Right Alternating Locomotor Circuitry
Authors: Rabe Nadine , Gezelius Henrik , Vallstedt Anna , Memic Fatima , Kullander Klas
Published: December 2009

Neuronal circuits in the spinal cord that produce the rhythmic and coordinated activities necessary for limb movements are referred to as locomotor central pattern generators (CPGs). The identities and preceding development of neurons essential for coordination between left and right limbs are not yet known. We show that the ventral floor plate chemoattractant Netrin-1 preferentially guides dorsally originating subtypes of commissural interneurons, the majority of which are inhibitory. In contrast, the excitatory and ventralmost V3 subtype of interneurons have a normal number of commissural fibers in Netrin-1 mutant mice, thus being entirely independent of Netrin-1-mediated attraction. This selective loss of commissural fibers in Netrin-1 mutant mice resulted in an abnormal circuitry manifested by a complete switch from alternating to synchronous fictive locomotor activity suggesting that the most ventral-originating excitatory commissural interneurons are an important component of a left-right synchrony circuit in the locomotor CPG. Thus, during development, Netrin-1 plays a critical role for the establishment of a functional balanced CPG.
Reliability of GaN on Si FETs and MMICs
Authors: Gajewski Donald A. , Nagy Walter , Hanson Allen W. , Johnson J.W. , Linthicum K J
Published: December 2009

This paper reviews the reliability results for the gallium nitride on silicon (GaN-on-Si) technologies for commercial and military communications markets. Two technology platforms have been qualified for volume production: one consisting of discrete heterostructure field effect transistors (HFETs) and the other consisting of HFETs integrated with passive components to form monolithic microwave integrated circuits (MMICs). The technology platform qualifications for volume production have been achieved through intrinsic reliability tests on the active and passive device elements as well as extrinsic reliability tests at the product level. This paper presents reliability results on accelerated life test (ALT), high temperature operating life under DC and RF stress (DC/RF-HTOL), electrostatic discharge (ESD), ramped voltage breakdown, electromigration, temperature cycling, robustness under voltage standing wave ratio (VSWR) mismatch conditions, and diode stability. Degradation and breakdown mechanisms are discussed in relation to material properties reliability. The results show that the HFET and MMIC technology platforms display reliable performance for 20 year product lifetime at worst case operating conditions.
Nanoscale Pattern Formation in Polyelectrolyte Gels
Authors: Jha Prateek K. , Solis Francisco J. , de Pablo Juan J. , Olvera de la Cruz Monica
Published: December 2009

Polyelectrolyte (PE) gels exhibit complex phase behavior that includes the existence of nanostructures in poor-solvent conditions. The formation of these inhomogeneous structures is made possible by the competition between the short-range hydrophobic, elastic, and entropic interactions and the long-range electrostatic forces. We develop a theoretical framework that describes the effect of monomer and charge inhomogeneities in PE gels. Numerical calculations performed on a salt-free PE gel with one-dimensional heterogeneities demonstrate the presence of nanophases for a finite range of physical parameters.
A PVA-PCL Bioglass Composite with Potential Implications for Osteochondral Tissue Engineering
Authors: Nair Prabha D , Mukundan Lakshmi M , Nirmal Remya , Mohan Neethu
Published: December 2009

A bioglass of composition SiO2 (67.12 mol%), CaO (28.5 mol%), and P2O5 (4.38%) was synthesized and stabilized by a novel technique using ethanol. Bioactive glasses have a wide range of application in the field of biomaterials promoting bone bonding as well as bonding to soft tissue. Earlier our lab developed a novel PVA-PCL semi IPN porous and 3D scaffold that was found to favor chondrogenesis. In the present study, a composite of this polymer and bioglass is prepared by an emulsion freeze-drying process, as a porous 3 dimensional scaffold. The scaffolds were characterized for their physiochemical properties and ability to support cartilage tissue regeneration. The composite scaffolds were observed to be non-cytotoxic. The chondrocytes cells cultured in vitro for a month on the composite scaffolds regenerate cartilaginous tissue, secreting GAGs and collagen in amounts nearly comparable to the amounts on the control PVA-PCL scaffold. The composite scaffold is also biomimetic and bioactive and favors mineralization by forming a hydroxycarbonate apatite layer, when immersed in simulated body fluid for a 14 day period. The PVA-PCL-bioglass composite is hence expected to have potential implications as a scaffold for osteochondral tissue engineering.
New 3D-Biophotopolymers with Selective Surface-cell Interactions for Regenerative Medicine
Authors: Heller Christian , Schwentenwein Martin , Varga Franz , Porodec Maja , Schulz-Siegmund Michaela , Russmueller Guenter , Stampfl Jurgen , Liska Robert
Published: December 2009

Additive Manufacturing Technologies (AMTs) have become an appealing method for the fabrication of 3D cellular scaffolds for tissue engineering and regenerative medicine. To circumvent the use of (meth)acrylate based photopolymers, that suffer from skin irritation and sometimes cytotoxicity, new monomers based on vinyl esters, carbonates and carbamates were prepared. The new materials, giving poly(vinyl alcohol) upon hydrolysis, showed similar results compared to (meth)acrylate references concerning the photoreactivity and mechanical properties, yet being significantly less cytotoxic.

To study the kinetics of hydrolytic degradation, the influence of the different polymerizable groups was investigated by hydrolysis of model compounds under alkaline conditions. We were able to show that the ester moiety of a vinyl ester based polymer could be used to immobilize alkaline phosphatase, therefore they exhibit the ability to immobilize enzymes for selective cell adhesion.

Finally, 3D test structures by AMT techniques could be fabricated and in-vivo testing thereof proofed the biocompatibility of vinyl ester-based scaffolds.
Do birds affect Lyme disease risk? Range expansion of the vector‐borne pathogen Borrelia burgdorferi
Authors: Brinkerhoff R Jory , Folsom-O'Keefe Corrine M , Tsao Kimberly , Diuk-Wasser Maria A
Published: December 2009

Because of their capacity for long‐range movement, birds may play an important role in the spread and range expansion of zoonotic pathogens and their vectors. The black‐legged tick (Ixodes scapularis) is the principal vector for the Lyme disease bacterium Borrelia burgdorferi, and commonly parasitizes a wide variety of vertebrate hosts, including at least 71 species of North American birds. Although the role of birds in B burgdorferi transmission dynamics is often discounted, data compiled from published studies indicate that the majority (58.6%) of bird species that have been evaluated are capable of infecting larval I scapularis with B burgdorferi. We estimated – for two bird species – that the number of individual birds required to produce one infected I scapularis larva is as low as three, and we conclude that bird‐mediated tick movement is an important factor in the range expansion of both I scapularis and B burgdorferi.
Model transformations to bridge concrete and abstract syntax of web rule languages
Authors: Milanovic Milan , Gasevic Dragan , Giurca Adrian , Wagner Gerd , Lukichev Sergey , Devedzic Vladan
Published: December 2009

This paper presents a solution to bridging the abstract and concrete syntax of a Web rule languages by using model transformations. Current specifications of Web rule languages such as Semantic Web Rule Language (SWRL) or RuleML define their abstract syntax (e.g., metamodel) and concrete syntax (e.g., XML schema) separately. Although the recent research in the area of Model-Driven Engineering (MDE) demonstrates that such a separation of two types of syntax is a good practice (due to the complexity of languages), one should also have tools that check validity of rules written in a concrete syntax with respect to the abstract syntax of the rule language. In this study, we use the REWERSE I1 Rule Markup Language (R2ML), SWRL, and Object Constraint Language (OCL), whose abstract syntax is defined by using metamodeling, while their textual concrete syntax is defined by using either XML/RDF schema or Extended Backus-Naur Form (EBNF) syntax. We bridge this gap by a bi-directional transformation defined in a model transformation language (ATLAS Transformation Language, ATL). This transformation allowed us to discover a number of issues in both web rule language metamodels and their corresponding concrete syntax, and thus make them fully compatible. This solution also enables for sharing web rules between different web rule languages.
A supervised manifold learning method
Authors: Li Zuojin , Shi Weiren , Shi Xin , Zhong Zhi
Published: December 2009

The Locally Linear Embedding (LLE) algorithm is an unsupervised nonlinear dimensionality-reduction method, which reports a low recognition rate in classification because it gives no consideration to the label information of sample distribution. In this paper, a classification method of supervised LLE (SLLE) based on Linear Discriminant Analysis (LDA) is proposed. First, samples are classified according to their label values, and low dimensional features of intraclass data are expressed through LLE manifold learning. Then, the base vectors in Fisher subspace of the low dimensional features are generated through LDA learning. This method increases inter-class variation, and decreases the intra-class variation when samples are projected to the Fisher subspace. Hence, the samples of different labels can be recognized, and the recognition rate and robustness of the LLE learning are improved. Experiments on handwritten digit recognition show that the proposed method is featuring high recognition rate.
Analysis of unsupervised dimensionality reduction techniques
Authors: Kumar Aswani
Published: December 2009

Domains such as text, images etc contain large amounts of redundancies and ambiguities among the attributes which result in considerable noise effects (i.e. the data is high dimension). Retrieving the data from high dimensional datasets is a big challenge. Dimensionality reduction techniques have been a successful avenue for automatically extracting the latent concepts by removing the noise and reducing the complexity in processing the high dimensional data. In this paper we conduct a systematic study on comparing the unsupervised dimensionality reduction techniques for text retrieval task. We analyze these techniques from the view of complexity, approximation error and retrieval quality with experiments on four testing document collections.
Increased Vitreous Shedding of Microparticles in Proliferative Diabetic Retinopathy Stimulates Endothelial Proliferation
Authors: Chahed Sadri , Leroyer Aurélie S. , Benzerroug Mounir , Gaucher David , Georgescu Adriana , Picaud Serge , Silvestre Jean-Sébastien , Gaudric Alain , Tedgui Alain , Massin Pascale , Boulanger Chantal M.
Published: December 2009

OBJECTIVE

Diabetic retinopathy is associated with progressive retinal capillary activation and proliferation, leading to vision impairment and blindness. Microparticles are submicron membrane vesicles with biological activities, released following cell activation or apoptosis. We tested the hypothesis that proangiogenic microparticles accumulate in vitreous fluid in diabetic retinopathy.

RESEARCH DESIGN AND METHODS

Levels and cellular origin of vitreous and plasma microparticles from control (n = 26) and diabetic (n = 104) patients were analyzed by flow cytometry, and their proangiogenic activity was assessed by in vitro thymidine incorporation and neovessel formation in subcutaneous Matrigel plugs in mice.

RESULTS

Microparticles of endothelial, platelet, photoreceptor, and microglial origin were identified in vitreous samples. Levels of photoreceptor and microglial microparticles were undetectable in plasmas but were comparable in diabetic and control vitreous samples. Vitreous platelet and endothelial microparticles levels were increased in diabetic patients and decreased following panretinal laser photocoagulation or intravitreal antivascular endothelial growth factor injection in proliferative diabetic retinopathy (PDR). The ratio of vitreous to plasma microparticle levels was calculated to estimate local formation versus potential plasma leakage. In PDR, the endothelial microparticles ratio—but not that for platelet—was greater than 1.0, indicating local formation of endothelial microparticles from retinal vessels and permeation of platelet microparticles from plasma. Isolated vitreous microparticles stimulated by 1.6-fold endothelial proliferation and increased new vessel formation in mice.

CONCLUSIONS

The present study demonstrates that vitreous fluid contains shed membrane microparticles of endothelial, platelet, and retinal origin. Vitreous microparticles levels are increased in patients with diabetic retinopathy, where they could contribute to disease progression.
Genetic Variation at the FTO Locus Influences RBL2 Gene Expression
Authors: Jowett Jeremy B.M. , Curran Joanne E. , Johnson Matthew P. , Carless Melanie A. , Göring Harald H.H. , Dyer Thomas D. , Cole Shelley A. , Comuzzie Anthony G. , MacCluer Jean W. , Moses Eric K. , Blangero John
Published: December 2009

OBJECTIVE

Genome-wide association studies that compare the statistical association between thousands of DNA variations and a human trait have detected 958 loci across 127 different diseases and traits. However, these statistical associations only provide evidence for genomic regions likely to harbor a causal gene(s) and do not directly identify such genes. We combined gene variation and expression data in a human cohort to identify causal genes.

RESEARCH DESIGN AND METHODS

Global gene transcription activity was obtained for each individual in a large human cohort (n = 1,240). These quantitative transcript data were tested for correlation with genotype data generated from the same individuals to identify gene expression patterns influenced by the variants.

RESULTS

Variant rs8050136 lies within intron 1 of the FTO gene on chromosome 16 and marks a locus strongly associated with type 2 diabetes and obesity and widely replicated across many populations. We report that genetic variation at this locus does not influence FTO gene expression levels (P = 0.38), but is strongly correlated with expression of RBL2 (P = 2.7 × 10−5), ∼270,000 base pairs distant to FTO.

CONCLUSIONS

These data suggest that variants at FTO influence RBL2 gene expression at large genetic distances. This observation underscores the complexity of human transcriptional regulation and highlights the utility of large human cohorts in which both genetic variation and global gene expression data are available to identify disease genes. Expedient identification of genes mediating the effects of genome-wide association study–identified loci will enable mechanism-of-action studies and accelerate understanding of human disease processes under genetic influence.
Lipotoxicity and Decreased Islet Graft Survival
Authors: Leitão Cristiane B. , Bernetti Karina , Tharavanij Thipaporn , Cure Pablo , Lauriola Vincenzo , Berggren Per-Olof , Ricordi Camillo , Alejandro Rodolfo
Published: December 2009

OBJECTIVE

To evaluate if baseline serum lipids are associated with islet graft survival in type 1 diabetes islet transplant (ITx) recipients.

RESEARCH DESIGN AND METHODS

Baseline fasting lipid profile was collected from 44 ITx recipients. Comparisons were performed between subjects below and above the median values of each lipid fraction. Differences in outcomes were compared by Kaplan-Meier curves and Cox regression analysis.

RESULTS

Subjects with baseline fasting plasma triglycerides and VLDL cholesterol above the median had shorter islet graft survival (triglycerides: 39.7 ± 6.1 vs. 61.3 ± 6.6 months, P = 0.029, and VLDL: 41.5 ± 5.7 vs. 62.8 ± 7.3 months, P = 0.032). Total, LDL, and HDL cholesterol did not influence islet function. Triglycerides (odds ratio 2.97 [95% CI 1.03–8.52], P = 0.044) maintained its association with graft failure after adjustments for confounders.

CONCLUSIONS

Higher baseline triglycerides are associated with earlier decline in islet graft function. Prospective clinical trials should address whether it is directly caused by lipotoxicity and if strategies focusing on lowering serum lipids may prolong islet graft survival.
A Synthesis of the C-11 Epimer of the Sesquiterpenoid 5-epi-kudtriol
Authors: Zhou Gang , Gao Xiaolei , Zhang Zhe , Li Yulin
Published: December 2009

The C-11 isomer of natural trihydroxyl sesquiterpene 5-epi-kudtriol 3 has been synthesized starting from (+)-dihydrocarvone via asymmetric dihydroxylation as a key step.
A New Polyoxygenated Steroid from the gorgonian Gorgonella umbraculum
Authors: Subrahmanyam Chitti , Kumar Sreekantha Ratna
Published: December 2009

A new polyoxygenated steroid, 1, has been isolated from the Indian ocean gorgonian Gorgonella umbraculum and its structure established from its spectral data.
A Simple and Efficient Oxidation of Hydrazides to N,N′-diacylhydrazines using Oxone® in an aqueous medium
Authors: Kulkarni P. P. , Kadam A. J. , Desai Uday V. , Mane R. B. , Wadgaonkar P. P.
Published: December 2009

Substituted aromatic hydrazides have been oxidised to N,N′-diacylhydrazines in high yields using Oxone in an aqueous medium at room temperature.
Kinetic and Mechanistic Studies of the Thermal Isomerization of Bismuth Dithizonate
Authors: Sueishi Yoshimi , Takashima Yoko
Published: December 2009

The isomerization rates of bismuth dithizonate (Bi(HD Z)3) having three dithizone ligands have been measured in various kinds of solvents and at high pressures, and the reaction mechanisms in aprotic and protic solvents are discussed.
Fries rearrangement of Arylsulfonates and Sulfonanilides under Microwave Irradiation
Authors: Das Biswanath , Madhusudhan Purushotham , Venkataiah Bollu
Published: December 2009

Fries rearrangements of arylsulfonates and sulfonanilides under microwave irradiation afforded hydroxy and aminoaryl sulfones respectively in very short times and in excellent yields. The conversion showed high selectivity to produce 2- and 4- hydroxyaryl sulfones as the major and minor products respectively from arylsulfonates and 2-aminoaryl sulfones exclusively from aryl sulfonanilides.
Synthesis of Highly Substituted Diphenylacetamides and Diphenylsulfonamides by the Goldberg Coupling Reaction
Authors: Raposo M. Manuela M. , Pereira Alexandra M.B. , Oliveira-Campos Ana M.F. , Shannon Patrick V.R.
Published: December 2009

We report the synthesis and characterisation of multisubstituted diphenylacetamides, diphenylsulfonamides and diphenylamines (and some observations on cyclisation of the last).
Condensation of α-cyanocinnamonitriles with 6-bromo-2-naphthol: Synthesis of pyrano [2,3-d]pyrimidine and pyrano[3,2-e] [1,2,4]triazolo[2,3-c]pyrimidine derivatives
Authors: Sayed Ahmed Z. , El-Hady Nagwa A. , El-Agrody Ahmed M.
Published: December 2009

Naphthopyrans are synthesized by the reaction of cinnamonitriles with 6-bromo-2-naphthol; polysubstituted naph-thopyrimidines and naphthopyranotriazolopyrimidines are also prepared.
Cu (OTf)2catalysed reactions of furan and thiophene with α,β-unsaturated ketones
Authors: Bulbule Vivek J. , Deshpande Vishnu H , Bedekar Ashutosh V.
Published: December 2009

Lewis acid catalysed electrophilic substitution reaction of furan and thiophene with α,β-unsaturated ketones, at ambient temperature is described.