bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood
Authors: Davies Matthew N , Volta Manuela , Pidsley Ruth , Lunnon Katie , Dixit Abhishek , Lovestone Simon , Coarfa Cristian , Harris R Alan , Milosavljevic Aleksandar , Troakes Claire , Al-Sarraj Safa , Dobson Richard , Schalkwyk Leonard C , Mill Jonathan
Published: December 2012

Background

Dynamic changes to the epigenome play a critical role in establishing and maintaining cellular phenotype during differentiation, but little is known about the normal methylomic differences that occur between functionally distinct areas of the brain. We characterized intra- and inter-individual methylomic variation across whole blood and multiple regions of the brain from multiple donors.

Results

Distinct tissue-specific patterns of DNA methylation were identified, with a highly significant over-representation of tissue-specific differentially methylated regions (TS-DMRs) observed at intragenic CpG islands and low CG density promoters. A large proportion of TS-DMRs were located near genes that are differentially expressed across brain regions. TS-DMRs were significantly enriched near genes involved in functional pathways related to neurodevelopment and neuronal differentiation, including BDNF, BMP4, CACNA1A, CACA1AF, EOMES, NGFR, NUMBL, PCDH9, SLIT1, SLITRK1 and SHANK3. Although between-tissue variation in DNA methylation was found to greatly exceed between-individual differences within any one tissue, we found that some inter-individual variation was reflected across brain and blood, indicating that peripheral tissues may have some utility in epidemiological studies of complex neurobiological phenotypes.

Conclusions

This study reinforces the importance of DNA methylation in regulating cellular phenotype across tissues, and highlights genomic patterns of epigenetic variation across functionally distinct regions of the brain, providing a resource for the epigenetics and neuroscience research communities.
GATA2-Induced Silencing and LIM-Homeodomain Protein-Induced Activation Are Mediated by a Bi-Functional Response Element in the Rat GnRH Receptor Gene
Authors: Schang Anne-Laure , Granger Anne , Quérat Bruno , Bleux Christian , Cohen-Tannoudji Joëlle , Laverrière Jean-Noël
Published: December 2012

GATA2 transcription factor and LIM homeodomain proteins Islet1 (ISL1) and LIM homeobox 3 (LHX3) are suspected to be involved in gonadotrope cell fate and maintenance. The GnRH receptor gene (Gnrhr), crucial for gonadotrope function, is expressed in the pituitary gland from embryonic day 13.5 onward, well before LH and FSH β-subunits. This expression pattern together with the presence of WGATAR and TAAT motifs in Gnrhr promoter sequences suggests the involvement of early transcription factors in promoter activation. In this study, using a well-characterized transgenic mouse model, GATA2 was found colocalized with Gnrhr promoter activity in the pituitary. Transient transfection of Gnrhr promoter luciferase fusion constructs together with either GATA2 expression vectors or small interfering RNA in gonadotrope cell lines indicated that GATA2, which typically acts as a trans-activator, unexpectedly repressed Gnrhr promoter activity. Using DNA chromatography affinity and EMSA, we demonstrated that GATA2 operates via a response element containing a peculiar palindromic GATA motif that overlaps a critical TAAT motif involved in LHX3/ISL1 trans-activation. Indeed, despite the inhibitory action of GATA2, this element displayed a clear-cut enhancer activity in gonadotrope cells. Chromatin immunoprecipitation assays indicated that GATA2, LHX3, and ISL1 interact with a Gnrhr promoter fragment encompassing this element. The trans-repressive action of GATA2 on Gnrhr promoter activity is likely balanced or even hindered by trans-activating effects of LIM homeodomain proteins via this novel bifunctional LIM/GATA response element. Such a hierarchical interplay may contribute to finely adjust Gnrhr gene expression in gonadotrope cell lineage during pituitary development as well as in the adult animal.
Asymptotic Properties of the Approximate Inverse Estimator for Directional Distributions
Authors: Riplinger M. , Spiess M.
Published: December 2012

For stationary fiber processes, the estimation of the directional distribution is an important task. We consider a stereological approach, assuming that the intersection points of the process with a finite number of test hyperplanes can be observed in a bounded window. The intensity of these intersection processes is proportional to the cosine transform of the directional distribution. We use the approximate inverse method to invert the cosine transform and analyze asymptotic properties of the estimator in growing windows for Poisson line processes. We show almost-sure convergence of the estimator and derive Berry–Esseen bounds, including formulae for the variance.
Convex Duality in Mean-Variance Hedging Under Convex Trading Constraints
Authors: Czichowsky Christoph , Schweizer Martin
Published: December 2012

We study mean-variance hedging under portfolio constraints in a general semimartingale model. The constraints are formulated via predictable correspondences, meaning that the trading strategy is restricted to lie in a closed convex set which may depend on the state and time in a predictable way. To obtain the existence of a solution, we first establish the closedness inL2of the space of all gains from trade (i.e. the terminal values of stochastic integrals with respect to the price process of the underlying assets). This is a first main contribution which enables us to tackle the problem in a systematic and unified way. In addition, using the closedness allows us to explain and generalise in a systematic way the convex duality results obtained previously by other authors via ad-hoc methods in specific frameworks.
Limit Theorems for Long-Memory Stochastic Volatility Models with Infinite Variance: Partial Sums and Sample Covariances
Authors: Kulik Rafał , Soulier Philippe
Published: December 2012

In this paper we extend the existing literature on the asymptotic behavior of the partial sums and the sample covariances of long-memory stochastic volatility models in the case of infinite variance. We also consider models with leverage, for which our results are entirely new in the infinite-variance case. Depending on the interplay between the tail behavior and the intensity of dependence, two types of convergence rates and limiting distributions can arise. In particular, we show that the asymptotic behavior of partial sums is the same for both long memory in stochastic volatility and models with leverage, whereas there is a crucial difference when sample covariances are considered.
Berry–Esseen Bounds and the Law of the Iterated Logarithm for Estimators of Parameters in an Ornstein–Uhlenbeck Process with Linear Drift
Authors: Jiang Hui
Published: December 2012

We study the asymptotic behaviors of estimators of the parameters in an Ornstein–Uhlenbeck process with linear drift, such as the law of the iterated logarithm (LIL) and Berry–Esseen bounds. As an application of the Berry–Esseen bounds, the precise rates in the LIL for the estimators are obtained.
Discounted Continuous-Time Controlled Markov Chains: Convergence of Control Models
Authors: Prieto-Rumeau Tomás , Hernández-Lerma Onésimo
Published: December 2012

We are interested in continuous-time, denumerable state controlled Markov chains (CMCs), with compact Borel action sets, and possibly unbounded transition and reward rates, under the discounted reward optimality criterion. For such CMCs, we propose a definition of a sequence of control models {ℳn} converging to a given control model ℳ, which ensures that the discount optimal reward and policies of ℳn converge to those of ℳ. As an application, we propose a finite-state and finite-action truncation technique of the original control model ℳ, which is illustrated by approximating numerically the optimal reward and policy of a controlled population system with catastrophes. We study the corresponding convergence rates.
On the Functional Central Limit Theorem for Reversible Markov Chains with Nonlinear Growth of the Variance
Authors: Longla Martial , Peligrad Costel , Peligrad Magda
Published: December 2012

In this paper we study the functional central limit theorem (CLT) for stationary Markov chains with a self-adjoint operator and general state space. We investigate the case when the variance of the partial sum is not asymptotically linear in n, and establish that conditional convergence in distribution of partial sums implies the functional CLT. The main tools are maximal inequalities that are further exploited to derive conditions for tightness and convergence to the Brownian motion.
Intraoperative Frozen Section Analysis of Margins in Breast Conserving Surgery Significantly Decreases Reoperative Rates
Authors: Jorns Julie M. , Visscher Daniel , Sabel Michael , Breslin Tara , Healy Patrick , Daignaut Stephanie , Myers Jeffrey L. , Wu Angela J.
Published: December 2012

Intraoperative frozen section (FS) margin evaluation is not common practice for patients undergoing breast conservation therapy (BCT), but offers a significant reduction in reoperation. In this study, a technique to allow for more effective freezing of breast tissue was developed to perform FS evaluation of lumpectomy margins (FSM) for all patients undergoing BCT at an ambulatory surgery center. FS evaluation of sentinel lymph node biopsy specimens was performed concurrently. One hundred eighty-one study and 188 control patients, with and without FS evaluation, were compared. Reexcision was reduced 34% (from 48.9% to 14.9%) and reoperation was reduced 36% (from 55.3% to 19.3%) with FS evaluation. Most of the decrease in reoperative rate was because of a decrease in the need for margin reexcision. The number of patients requiring 1, 2, or 3 operations to complete therapy was 84, 92, and 12, respectively, in the control group, and 146, 33, and 2, respectively, in the study group. Lobular subtype, multifocal disease, and larger tumor size (≥2 cm) were significantly associated with failure of FSM to prevent reoperation, but reoperation rates were still significantly decreased in this subgroup of patients (from 75.5% to 43.8%) with FSM. This study highlights an innovative yet simple and adaptable FS approach that resulted in a nearly 3-fold reduction in reoperation for patients undergoing BCT.
Molecular Diagnostics of Melanoma Fine-Needle Aspirates
Authors: Bernacki Kurt D. , Betz Bryan L. , Weigelin Helmut C. , Lao Christopher D. , Redman Bruce G. , Knoepp Stewart M. , Roh Michael H.
Published: December 2012

Patients with advanced-stage melanoma harboring a BRAF mutation are candidates for BRAF inhibition as a therapeutic strategy. The use of fine-needle aspiration (FNA) to diagnose metastatic melanoma is increasing. Studies examining the predictive value of BRAF mutation analysis on melanoma FNAs via correlation with follow-up excision findings are lacking. We examined 37 consecutive FNA cases of metastatic melanoma in which the aspirated lesion was subsequently excised. DNA was purified from Diff-Quik–stained FNA smears and tissue blocks from corresponding excisions in parallel. BRAF mutation status was successfully obtained from both specimen types in 34 (92%) of 37 cases. BRAF mutations were detected in 12 (35%) of 34 cases—11 V600E and 1 V600K. Results of BRAF mutational analysis were concordant in all 34 FNA smear/tissue excision pairs. Thus, melanoma FNA for molecular diagnostics represents a rapid, minimally invasive, and effective management strategy in this era of precision medicine.
Prognostic Significance of the Ratio of Absolute Neutrophil Count to Absolute Lymphocyte Count in Classic Hodgkin Lymphoma
Authors: Koh Young Wha , Kang Hyo Jeong , Park Chansik , Yoon Dok Hyun , Kim Shin , Suh Cheolwon , Kim Ji Eun , Kim Chul-Woo , Huh Jooryung
Published: December 2012

The aim of this study was to determine the prognostic effect of the absolute neutrophil count/absolute lymphocyte count ratio (ANC/ALC ratio) in patients with classic Hodgkin lymphoma (cHL). We performed a retrospective analysis of 312 patients with cHL. Univariate analysis revealed that a high ANC/ALC ratio (≥4.3) correlated with poor overall survival (OS) (P < .001). Subgroup analysis of advanced-stage disease showed that the ANC/ALC ratio was significant for OS (P = .032). Multivariate analysis revealed the ANC/ALC ratio to be an independent prognostic factor for OS (P = .048). The ANC/ALC ratio allowed further risk stratification in patients who were considered to be at low risk on the basis of an International Prognostic Score less than 4 (P = .002). The ANC/ALC ratio is a simple, inexpensive, and independent prognostic factor for OS that may improve the ability to identify high-risk patients with cHL.
Patterned Deposition of Allophane Nanoparticles on Silicon Substrates
Authors: Fuchs Marco , Abidin Zaenal , Kübel Christian , Weidler Peter G. , Matsue Naoto , Henmi Teruo , Köster Rainer , Gliemann Hartmut
Published: December 2012

In order to obtain nanopatterned surfaces, natural allophane particles originating from Japanese soils were immobilized as single particles on Si wafer substrates.When derived from aqueous suspensions, only a few nanoparticles were deposited and detected on the surface due to the weak adsorption of allophanes on the substrate. The amount of immobilized allophane was increased significantly, however, by using an organic solvent in combination with a micelle-based technique to suspend the allophane particles. The micelles were formed from a tailored, aliphatic diblock copolymer that was dissolved in toluene and contained several allophane particles. A cleaned silica chip was used as a substrate on which a monolayer of micelles was immobilized equidistant from each other by dip coating. To remove the polymer from the substrate and to produce free, single allophane nanoparticles, ultraviolet (UV) irradiation was used. After UV treatment, single allophane particles formed ring-shaped deposition patterns with a high surface density. Transmission electron microscopy (TEM) was used to verify the presence of single allophane nanoparticles in the Japanese samples which came from natural sources. The single allophane particles as well as the allophane-containing di-block copolymer micelles, both immobilized on Si substrates and TEM sample grids, were imaged by atomic force microscopy and TEM. In this way, the diameters of the single allophane particles, as well as the distances between the immobilized micelles and the particles and their topography on the substrates, were determined.
Quantification of Hematite and Goethite Concentrations in Kaolin Using Diffuse Reflectance Spectroscopy: A New Approach To Kubelka-Munk Theory
Authors: Gomes Gonçalves Ítalo , Petter Carlos Otávio , Lepkoski Machado Jaqueline
Published: December 2012

Kaolin ores are usually contaminated by some Fe-bearing minerals, the strong colors of which degrade the quality of the final product. A spectroscopic technique is sought to quantify the content of hematite and goethite, the main contaminant minerals in the kaolin from Capim River in Brazil, was the focus of this study. The total Fe content obtained through X-ray fluorescence showed a poor correlation with the brightness of kaolin, due to the inability to differentiate between the Fe contained in the (oxyhydr)oxides and the Fe present in the crystalline structure of kaolinite, especially when the Fe-bearing minerals occur in small quantities. Here, a new generic technique to quantify Fe (oxyhydr)oxides in kaolin, based on the Kubelka-Munk theory, is presented. A new interpretation of the theory was made that enables its use without the need to measure thin layers of material. The results with synthetic goethite and hematite were very positive (R2pred ≈ 0.99) and experiments with contaminants from the mine are already underway.
Isotope-Dilution Liquid Chromatography–Tandem Mass Spectrometry Candidate Reference Method for Total Testosterone in Human Serum
Authors: Botelho Julianne Cook , Shacklady Christopher , Cooper Hans C , Tai Susan S-C , Uytfanghe Katleen Van , Thienpont Linda M , Vesper Hubert W
Published: December 2012

BACKGROUND

We developed and evaluated a candidate reference measurement procedure (RMP) to standardize testosterone measurements, provide highly accurate and precise value assignments for the CDC Hormone Standardization Program, and ensure accurate and comparable results across testing systems and laboratories.

METHODS

After 2 liquid/liquid extractions of serum with a combination of ethyl acetate and hexane, we quantified testosterone by isotope-dilution liquid chromatography–tandem mass spectrometry with electrospray ionization in the positive ion mode monitoring 289→97 m/z (testosterone) and 292→112 m/z (3C13 testosterone). We used calibrator bracketing and gravimetric measurements to give higher specificity and accuracy to serum value assignments. The candidate RMP was evaluated for accuracy by use of NIST-certified reference material SRM971 and validated by split-sample comparison to established RMPs. We evaluated intraassay and interassay imprecision, measurement uncertainty, potential interferences, and matrix effects.

RESULTS

A weighted Deming regression comparison of the candidate RMP to established RMPs showed agreement with no statistical difference (slope 0.99, 95% CI 0.98–1.00, intercept 0.54, 95% CI −1.24 to 2.32) and a bias of ≤0.3% for NIST SRM971. The candidate RMP gave maximum intraassay, interassay, and total percent CVs of 1.5%, 1.4%, and 1.7% across the concentrations of testosterone typically found in healthy men and women. We tested structural analogs of testosterone and 125 serum samples and found no interferences with the measurement.

CONCLUSIONS

This RMP for testosterone can serve as a higher-order standard for measurement traceability and can be used to provide an accuracy base to which routine methods can be compared in the CDC Hormone Standardization Program.
Physicians' Perceived Barriers to Promoting Smoking Cessation
Authors: Berlin Ivan
Published: December 2012

Background/Aims: Physicians' reluctance to promoting smoking cessation reduces the effectiveness of evidence-based recommendations resulting in suboptimal patient outcomes. Primary aim: to draw together findings from studies that addressed physicians' perceived barriers to promoting smoking cessation. Secondary aim: to assess whether interventions for reducing such perceived barriers impact on smoking cessation rates. Methods: Literature search in peer-reviewed journals focused on physicians' perceived barriers to addressing smoking cessation or on intervention studies aimed at alleviating these barriers. Results: The most frequently reported perceived barriers were: time constraints, high workload, lack of training, lack of reimbursement of smoking cessation interventions and the physician's own smoking status. Low outcome expectancy, lack of self-efficacy, fear of losing patients, being uncomfortable to discuss smoking hazards, dissatisfaction with professional activity were also reported. Smoking quit rates of intervention studies aimed to reduce perceived barriers varied according to the barrier targeted. Conclusion: Primary care physicians report a great number of perceived barriers to addressing smoking cessation. Results of intervention studies designed to reduce specific barriers with the purpose of increasing quit rates, remain conflicting. Multilevel intervention studies seem to be needed to assess the efficacy of alleviating perceived barriers to addressing smoking cessation.
Adult Neuronal Arf6 Controls Ethanol-Induced Behavior with Arfaptin Downstream of Rac1 and RhoGAP18B
Authors: Peru y Colón de Portugal Raniero L. , Acevedo Summer F. , Rodan Aylin R. , Chang Leo Y. , Eaton Benjamin A. , Rothenfluh Adrian
Published: December 2012

Alcohol use disorders affect millions of individuals. However, the genes and signaling pathways involved in behavioral ethanol responses and addiction are poorly understood. Here we identify a conserved biochemical pathway that underlies the sedating effects of ethanol inDrosophila. Mutations in the Arf6 small GTPase signaling pathway cause hypersensitivity to ethanol-induced sedation. We show that Arf6 functions in the adult nervous system to control ethanol-induced behavior. We also find that theDrosophilaArfaptin protein directly binds to the activated forms of Arf6 and Rac1 GTPases, and mutants inArfaptinalso display ethanol sensitivity. Arf6 acts downstream of Rac1 and Arfaptin to regulate ethanol-induced behaviors, and we thus demonstrate that this conserved Rac1/Arfaptin/Arf6 pathway is a major mediator of ethanol-induced behavioral responses.
Necessary, Sufficient and Permissive: A Single Locomotor Command Neuron Important for Intersegmental Coordination
Authors: Puhl Joshua G. , Masino Mark A. , Mesce Karen A.
Published: December 2012

In this report we posed the overarching question: What multiple contributions can a single neuron have on controlling the behavior of an animal, especially within a given context? To address this timely question, we studied the neuron R3b-1 in the medicinal leech. This bilaterally paired neuron descends from the cephalic ganglion and projects uninterrupted through the segmental ganglia comprising the nerve cord; its terminal arbors invade each hemi-ganglion. We discovered that a single R3b-1 neuron functions as a command neuron in the strictest sense, as it was both necessary and sufficient for fictive crawling behavior. Aside from these command-related properties, we determined that R3b-1 modulates the cycle period of crawl motor activity. R3b-1 has previously been shown to activate swimming behavior, but when the CNS was exposed to dopamine (DA), crawling became the exclusive locomotor pattern produced by R3b-1. DA exposure also led to bursting in R3b-1 that matched periods observed during fictive crawling, even when potential ascending inputs from crawl oscillators were removed. Although the above attributes render R3b-1 an intriguing cell, it is its ability to permit the coordination of the segmentally distributed crawl oscillators that makes this multifunctional neuron so notable. To our knowledge, this cell provides the first biological example of a single command neuron that is also vital for the intersegmental coordination of a locomotor behavior. Furthermore, our study highlights the importance of DA as an internal contextual cue that can integrate functional layers of the nervous system for adaptive behavior.
Rebalance of Striatal NMDA/AMPA Receptor Ratio Underlies the Reduced Emergence of Dyskinesia During D2-Like Dopamine Agonist Treatment in Experimental Parkinson's Disease
Authors: Bagetta Vincenza , Sgobio Carmelo , Pendolino Valentina , Del Papa Giulia , Tozzi Alessandro , Ghiglieri Veronica , Giampà Carmela , Zianni Elisa , Gardoni Fabrizio , Calabresi Paolo , Picconi Barbara
Published: December 2012

Dopamine replacement with levodopa (l-DOPA) represents the mainstay of Parkinson's disease (PD) therapy. Nevertheless, this well established therapeutic intervention loses efficacy with the progression of the disease and patients develop invalidating side effects, known in their complex asl-DOPA-induced dyskinesia (LID). Unfortunately, existing therapies fail to prevent LID and very few drugs are available to lessen its severity, thus representing a major clinical problem in PD treatment. D2-like receptor (D2R) agonists are a powerful clinical option as an alternative tol-DOPA, especially in the early stages of the disease, being associated to a reduced risk of dyskinesia development. D2R agonists also find considerable application in the advanced stages of PD, in conjunction withl-DOPA, which is used in this context at lower dosages, to delay the appearance and the extent of the motor complications. In advanced stages of PD, D2R agonists are often effective in delaying the appearance and the extent of motor complications. Despite the great attention paid to the family of D2R agonists, the main reasons underlying the reduced risk of dyskinesia have not yet been fully characterized. Here we show that the striatal NMDA/AMPA receptor ratio and the AMPA receptor subunit composition are altered in experimental parkinsonism in rats. Surprisingly, whilel-DOPA fails to restore these critical synaptic alterations, chronic treatment with pramipexole is associated not only with a reduced risk of dyskinesia development but is also able to rebalance, in a dose-dependent fashion, the physiological synaptic parameters, thus providing new insights into the mechanisms of dyskinesia.
Astrocyte-Specific Overexpression of Nrf2 Delays Motor Pathology and Synuclein Aggregation throughout the CNS in the Alpha-Synuclein Mutant (A53T) Mouse Model
Authors: Gan Li , Vargas Marcelo R. , Johnson Delinda A. , Johnson Jeffrey A.
Published: December 2012

Alpha synuclein (SYN) is a central player in the pathogenesis of sporadic and familial Parkinson's disease (PD). SYN aggregation and oxidative stress are associated and enhance each other's toxicity. It is unknown whether the redox-sensitive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a role against the toxicity of SYN. To examine this, mice selectively overexpressing Nrf2 in astrocytes (GFAP-Nrf2) were crossed with mice selectively expressing human mutant SYN (hSYNA53T) in neurons. Increased astrocytic Nrf2 delayed the onset and extended the life span of the hSYNA53Tmice. This correlated with increased motor neuron survival, reduced oxidative stress, and attenuated gliosis in the spinal cord, as well as a dramatic decrease in total hSYNA53Tand phosphorylated (Ser129) hSYNA53Tin Triton-insoluble aggregates. Furthermore, Nrf2 in astrocytes delayed chaperone-mediated autophagy and macroautophagy dysfunction observed in the hSYNA53Tmice. Our data suggest that Nrf2 in astrocytes provides neuroprotection against hSYNA53T-mediated toxicity by promoting the degradation of hSYNA53Tthrough the autophagy-lysosome pathwayin vivo. Thus, activation of the Nrf2 pathway in astrocytes is a potential target to develop therapeutic strategies for treating pathologic synucleinopathies including PD.
All Layers of Medial Entorhinal Cortex Receive Presubicular and Parasubicular Inputs
Authors: Canto Cathrin B. , Koganezawa Noriko , Beed Prateep , Moser Edvard I. , Witter Menno P.
Published: December 2012

The medial entorhinal cortex (MEC), presubiculum (PrS), and parasubiculum (PaS) are interconnected components of the hippocampal–parahippocampal spatial-representation system. Principal cells in all layers of MEC show signs of directional tuning, overt in head direction cells present in all layers except for layer II, and covert in grid cells, which are the major spatially modulated cell type in layer II. Directional information likely originates in the head direction-vestibular system and PrS and PaS are thought to provide this information to MEC. Efferents from PaS and PrS show a selective laminar terminal distribution in MEC superficial layers II and III, respectively. We hypothesized that this anatomically determined laminar distribution does not preclude monosynaptic interaction with neurons located in deeper layers of MEC in view of the extensive apical dendrites from deeper cells reaching layers II and III. This hypothesis was tested in the rat using tiltedin vitroslices in which origins and terminations of PrS and PaS fibers were maintained, as assessed using anterograde anatomical tracing. Based on voltage-sensitive dye imaging, multipatch single-cell recordings, and scanning photostimulation of caged glutamate, we report first that principal neurons in all layers of MEC receive convergent monosynaptic inputs from PrS and PaS and second, that elicited responses show layer-specific decay times and frequency-dependent facilitation. These results indicate that regardless of their selective laminar terminal distribution, PrS and PaS inputs may monosynaptically convey directional information to principal neurons in all layers of MEC through synapses on their extensive dendritic arbors.
Removal of Default State-Associated Inhibition during Repetition Priming Improves Response Articulation
Authors: Dacks Andrew M. , Siniscalchi Michael J. , Weiss Klaudiusz R.
Published: December 2012

Behavior is a product of both the stimuli encountered and the current internal state. At the level of the nervous system, the internal state alters the biophysical properties of, and connections between, neurons establishing a “network state.” To establish a network state, the nervous system must be altered from an initial default/resting state, but what remains unclear is the extent to which this process represents induction from a passive default state or the removal of suppression by an active default state. We use repetition priming (a history-dependent improvement of behavioral responses to repeatedly encountered stimuli) to determine the cellular mechanisms underlying the transition from the default to the primed network state. We demonstrate that both removal of active suppression and induction of neuron excitability changes each contribute separately to the production of a primed state. The feeding system ofAplysia californicadisplays repetition priming via an increase in the activity of the radula closure neuron B8, which results in increased bite strength with each motor program. We found that during priming, B8 received progressively less inhibitory input from the multifunctional neurons B4/5. Additionally, priming enhanced the excitability of B8, but the rate at which B8 activity increased as a result of these changes was regulated by the progressive removal of inhibitory input. Thus, the establishment of the network state involves the induction of processes from a rested state, yet the consequences of these processes are conditional upon critical gating mechanisms actively enforced by the default state.
The Philippines Waltzes with the Big Boys: Coalition-building Strategy in the WTO
Authors: Quinsaat Sharon Madriaga
Published: December 2012

This article explores the emergence and development of the Philippine coalition-building strategy in the World Trade Organization (WTO) from the Uruguay Round to the Doha Development Agenda. Coalition building is an outcome of social learning, adaptation, and bounded rationality of trade negotiators based on years of working within the norms of the WTO.
“A Bryn Mawr School in the East”: Transpacific Initiatives for Japanese Women's Higher Education
Authors: Pamonag Febe
Published: December 2012

With crucial help from American women, Tsuda Umeko founded Joshi Eigaku Juku (JEJ), one of the first private women's colleges in Japan. This article examines Tsuda's strategies for seeking assistance from Bryn Mawr College and the latter's response from 1900 to the mid-1910s. Tsuda and her Bryn Mawr supporters' fund-raising efforts for JEJ were anchored on intersecting arguments that higher education was a means to elevate the conditions of Japanese women and JEJ was an extension of Bryn Mawr. Amid strained U.S.-Japanese relations, Tsuda also argued that JEJ was a bridge across the Pacific. This study illuminates the complexity of a transnational initiative for Japanese women by showing how it reflected and helped sustain differences among women and among nations.
Melanocortin 4 receptor distribution in the human hypothalamus
Authors: Siljee Jacqueline E , Unmehopa Unga A , Kalsbeek Andries , Swaab Dick F , Fliers Eric , Alkemade Anneke
Published: December 2012

Objective

The melanocortin 4 receptor (MC4R) is an essential regulator of energy homeostasis and metabolism, andMC4Rmutations represent the most prevalent monogenetic cause of obesity in humans known to date. Hypothalamic MC4Rs in rodents are well characterized in neuroanatomical and functional terms, but their expression pattern in the human hypothalamus is unknown.

Design and methods

To determine the topographic distribution and identity of cells expressingMC4RmRNA in the human hypothalamus, locked nucleic acidin situhybridization was performed on nine human postmortem hypothalami. In addition, co-expression ofMC4Rwith glial fibrillary acidic protein (GFAP), vasopressin/oxytocin (AVP/OXT), corticotropin-releasing hormone (CRH), neuropeptide Y (NPY), agouti-related protein (AgRP), and α-melanocyte stimulating hormone (α-MSH) was examined.

Results

Most intenseMC4RmRNA expression was present in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and the nucleus basalis of Meynert. MostMC4R-positive cells in the SON also expressed AVP/OXT. Co-expression with AVP/OXT in the PVN was less abundant. We did not observe co-expression ofMC4RmRNA and GFAP, CRH, NPY, AgRP, or α-MSH. However, fiber-like staining of NPY, AgRP, and α-MSH was found adjacent toMC4R-positive cells in the PVN.

Conclusion

Expression ofMC4RmRNA in the human hypothalamus is widespread and in close approximation to endogenous MC4R binding partners AgRP and α-MSH.
Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis
Authors: Abs Roger , Mattsson Anders F , Thunander Maria , Verhelst Johan , Góth Miklós I , Wilton Patrick , Kołtowska-Häggström Maria , Luger Anton
Published: December 2012

Objective

GH deficiency (GHD) in adults is characterized by a tendency toward obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed PP over expected PP ratio (standardized prevalence proportion ratio, SPR) of diabetes according to International Diabetes Federation criteria in a large cohort of GH-untreated adult-onset GHD patients.

Design and methods

Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the nondiabetic patients were done with covariance analysis. P values <0.05 were considered statistically significant.

Results

PP was 9.3% compared with the expected 8.2%. SPR was 1.13 (95% confidence intervals (95% CIs), 1.04–1.23), which was significantly increased in females (1.23; 95% CI, 1.09–1.38%) but not in males (SPR 1.04; 95% CI, 0.92–1.17%). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies, and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference, and IGF1 SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0–6.5% were found in 9.5% of nondiabetic patients and were associated with higher BMI and waist circumference.

Conclusions

GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge toward early initiation of lifestyle modification measures.
Measurements of Residual Stresses in Low-Stress Silicon Nitride Thin Films Using Micro-Rotating Structures
Authors: Zhang Xin , Zohar Yitshak , Zhang Tong-Yi
Published: December 2012

A variety of rotating micro structures were designed, fabricated and characterized for residual-stress (or strain) measurements in low-stress silicon nitride thin films, deposited by LPCVD on silicon wafers. The sensitivities of the micro structures were calculated by finite element method (FEM) and verified experimentally. The results were further confirmed by utilizing the wafer-curvature method for stress measurements. The size of the structures enables local residual-stress (or strain) measurement. The stress level depends on both the film thickness and the gas ratio and also varies with the location on the wafer.
Current Understanding and Modeling of Boron-Interstitial Clusters
Authors: Pichler Peter
Published: December 2012

Scaling of devices requires not only shallow junctions but also high levels of dopant activation. For boron as the main p-type dopant, the latter requirement is especially problematic since small clusters of boron atoms and self-interstitials, known also as boron-interstitial clusters (BICs), were found to deactivate and immobilize large fractions of the implanted atoms during post-implantation annealing. In this article, the properties of BICs are reviewed and their influence on semiconductor processes are highlighted.
Pulsed Force-Scanning Spreading Resistance Microscopy (PF-SSRM) for High Spatial Resolution 2D-dopant Profiling.
Authors: Eyben P. , Fouchier M. , Albart P. , Charon-Verstappen J. , Vandervorsta W.
Published: December 2012

Scanning Spreading Resistance Microscopy (SSRM) is now widely used for two-dimensional doping profiling with high spatial resolution. The need for a high force between the tip and the sample in order to obtain a good electrical contact, leads to a fast degradation of the tip (and the sample) while scanning. Tip damage is mainly due to the shear force occurring while scanning in contact mode at high forces leading to breakage (cleavage) of sharp tips or a rapid increase of tip radius (wear). The latter adversely affects the accuracy of the electrical measurements, as the contact radius is a determining parameter for quantification. The strong abrasive force also necessitates the use of tips composed of very hard material such as doped diamond, which has however a limited resistivity, and so far prevented the use of metallic probes. In addition the high force also prevents the simultaneous acquisition of high quality topography data. The solution to these problems is obtained by implementing the Modulated Force Principle (MFP). The latter consists of applying a variable (for instance pulsed) force while scanning, reducing the force during the lateral movement of the tip and synchronizing the electrical measurements with the high force periods. The latter results in lower lateral forces and introduces a quasi multi point contact mode. MFP also allows to obtain a better topography image by synchronizing the topography measurement with the low force part of the force cycle. The MFP leads to a drastic reduction of the surface and probe damage while maintaining high quality electrical data. The implementation of multiplexed detectors within the force cycle further enables the simultaneous acquisition of spreading resistance and topography during one scan, and/or the combination with multiple linear current detectors, capacitance sensors or tunneling current measurements.
Probing the AlxGa1-xN Atomic Distribution via UV-Photoluminescence and Raman at Sub-νm Scale
Authors: Bergman Leah , Chen Xiang-Bai , Householder Tim , McIlroy David , Yeh Wei Jiang , Terrell Stephen , Davis Robert F.
Published: December 2012

The spatial dependence of the band-gap light-emission energy of AlxGa1-xN alloys at composition 0≤ × ≤1 was studied via deep UV-photoluminescence (PL) and Raman microscopy. The data were acquired in a random fashion from an area of ∼ 1mm2 on the sample at steps of ∼1 νm - 200 νm utilizing the 244 nm laser line of probing spot size ∼300 nm radius. Our study indicates that the PL emission energy exhibits random type variations depending on locality: the alloys of composition x=0.12, x=0.22, and x=0.70 exhibit variations of ∼ 10 meV, 30 meV, and 25 meV respectively. The PL of the pure GaN exhibits no spatial dependence while the alloy of x=0.50 exhibits a variation around ∼ 45 meV. Moreover, the functional dependence of the band-gap Eg, on the composition was found to be Eg(x)=3.4(1-x)+6.2x-1.2x(1-x) from which the compositional variation, δx, can be computed for a given variation in the PL emission energy after accounting for the stress effect in the alloys.
Preparation and Characterization of Nanostructured FeS2 and CoS2 for High-Temperature Batteries
Authors: Guidotti Ronald A. , Reinhardt Frederick W. , Dai Jinxiang , Reisner David E.
Published: December 2012

In this paper, we report on the preparation of synthetic FeS2 and CoS2 using a relatively inexpensive aqueous process. This avoids the material and handling difficulties associated with a high-temperature approach. An aqueous approach also allows ready scale-up to a pilot-plant size facility. The FeS2 and CoS2 were characterized with respect to their physical and chemical properties. The synthetic disulfides were incorporated into catholyte mixes for testing in single cells and batteries over a range of temperatures. The results of these tests are presented and compared to the performance of natural FeS2 (pyrite) and a commercial source of CoS2.
High Performance Organic Thin Film Transistors
Authors: Kelley Tommie W. , Muyres Dawn V. , Baude Paul F. , Smith Terry P. , Jones Todd D.
Published: December 2012

We report here methods of surface modification and device construction which consistently result in lab-scale pentacene-based TFTs with mobilities at or above 5 cm2/Vs. Surface modifications include polymeric ultrathin films presenting a passivated interface on which the semiconductor can grow. High performance TFTs have been fabricated on a variety of dielectric materials, both organic and inorganic, and are currently being implemented in manufacturable constructions. Our surface modifications have also proven useful for substituted pentacene materials and for a variety of other organic semiconductors. In addition, we report an all organic active layer, rf-powered integrated circuit. Further experiments and statistical analyses are underway to explain the elevated mobility in our samples, and efforts have been made to confirm these results through collaboration.
Molecular Design, Synthesis and Luminescent Properties of Erbium(III)-Cored Supramolecular Complexes Based on Metalloporphyrins for Optical Amplification
Authors: Oh Jae Buem , Paik Kyung Lim , Ka Jae-Won , Roh Soo-Gyun , Nah Min Kook , Kim Hwan Kyu
Published: December 2012

We have investigated the development of erbium(III)-cored supramolecular complexes containing metalloporphyrins to circumvent the solubility problem and improve the optical amplification property. The new synthetic methodology was accomplished through the ligand-exchange model reaction using ErCl3 to optimize its synthetic condition We have designed and synthesized the model complexes to investigate coordination property between the ligand and the erbium ion. Highly coordinated erbium(III)-cored model complexes (at least 8 to 10 coordination) showed the strong near infrared(IR) emission at 1520 nm, corresponding to the 4I13/2 → 4I15/2 transition. Also, with these synthetic results, erbium(III)-cored supramolecular complexes based on metalloporphyrins were synthesized and characterized. They also showed the infrared emission of the 4I13/2 → 4I15/2 transition at 1520 nm.
Oxidation Of Si / nc-Ge / Si Heterostructures For Non Volatile Memory Applications
Authors: Kanoun M. , Souifi A. , Decossas S. , Dubois C. , Bremond G. , Bassani F. , Lim Y. , Ronda A. , Berbezier I. , Kermarrec O. , Bensahel D.
Published: December 2012

In this work, we present an extensive study of the oxidation process of Si/Ge nanocrystals (nc-Ge)/Si samples using SIMS (Second Ion Mass Spectroscopy), Transmission Electron Micrscopy (TEM), Atomic Force Microscopy (AFM) and electrical characterization of Metal/Oxide/Semiconductor capacitors (MOS). Various samples with different oxidation times have been studied and it is demonstrated that Silicon dry oxidation kinetics is not influenced by the presence of Ge. As shown by SIMS measurements, a pure SiO2 layer is formed on the top of the structure, while the Ge atoms are intermixed with the silicon substrate. The TEM and AFM analysis show that the nc-Ge height is drastically reduced during the oxidation process. The fabrication of MOS capacitors on the structures allowed to study electron and hole trapping in the Ge dots. From our analysis we have shown that the Ge nanostructures which covered by SiO2 are not isolated from the Si substrate.
Structural evolution and acoustic phonon behavior in crystalline PTFE latex films
Authors: Pierno M. , Casari C.S. , Bassi A. Li , Beghi M.G. , Piazza R. , Bottani C.E.
Published: December 2012

The structural evolution of polytetrafluoroethylene (PTFE) crystalline polymer latex films is studied at hundreds nanometer length scale by atomic force microscopy and Brillouin light scattering. In a controlled sintering process the transition is observed from the original particle distribution towards a ‘fibrillar’ structure of crystalline regions embedded in a disordered matrix. This transition is accompanied by a cross-over from localized acoustic excitations to propagating acoustic phonons, related to mesoscopic elastic properties. After sintering, a ‘mark’ of the original particulate structure persists, suggesting that filming of crystalline polymers may be analogous to sintering of ceramic powders. Films of crystalline polymers can thus be exploited as model systems to study the elasto-optical properties of granular and disordered media.
Mechanisms of Low-Temperature Ti/Si-Based Wafer Bonding
Authors: Yu Jian , Wang Yinmin , Haberl Arthur W. , Bakhru Hassa , Lu Jian-Qiang , Gutmann Ronald J.
Published: December 2012

Three-dimensional (3D) wafer-level integration is receiving increased attention with various wafer bonding approaches being evaluated. Recently, we explored an alternative lowtemperature Ti/Si-based wafer bonding, in which an oxidized silicon wafer was successfully bonded with a prime silicon wafer at 400°C using 30 nm sputtered Ti as adhesive. The bonded pairs show excellent bonding uniformity and mechanical integrity. Rutherford backscattering spectrometry (RBS) was applied to confirm the interdiffusion occurred in the interlayer. The bonding interface was examined by high-resolution transmission electron microscopy (HRTEM) assisted with electron energy loss spectroscopy (EELS) elemental mapping and energy dispersive X-ray spectroscopy (EDX). Characterization of the bonding interface indicates the strong adhesion achieved is attributed to an amorphous layer formed by interdiffusion of Si and oxygen into Ti interlayer and the unique ability to reduce native oxide (SiO2) by Ti even at low temperatures.
Modeling the Organic Thin Film Transistors
Authors: Olariu Viorel , Rotzoll Robert , Mohapatra Siddharth , Wenz Robert , Grigas Michelle , Dimmler Klaus
Published: December 2012

Organic thin-film transistors (OTFTs) appear to have become strong contenders to silicon based MOSFET devices whenever low-cost and relatively low performance circuits are required in applications such as radio frequency identification (RFID) for large volume supply chains. In order to develop circuits based on OTFTs, circuit designers require circuit models that predict the operation of OTFT with a reasonable accuracy. Although, generally, OTFT operation is similar to ordinary silicon MOSFET devices, there are several characteristics that clearly differentiate them. One important difference between the operation of the OTFT and the silicon MOSFET (that is a direct consequence of the physical implementation of OTFT) is that the organic transistor is normally operated in the accumulation mode, while the silicon transistor regularly operates in the inversion mode. Due to the molecular nature of the semiconductor, the carrier mobility is orders of magnitude lower than for the silicon MOSFET. Variable carrier mobility law, low on/off ratio, and the Schottky barrier at the interface between the source/drain metal contact and the organic semiconductor are among other important effects that had to be considered for developing of an accurate circuit model of the organic transistor. The developed model has been used to simulate DC characteristics and also simple circuits such as logic gates, ring oscillators, rectifiers, etc.

This paper presents the developed model as well as a comparison between the simulated data and the experimental data. The experimental circuits were fabricated on flexible plastic substrates and employed a solution-cast dielectric. Pentacene was the semiconductor of choice with carrier mobility in the range of 0.1 – 1.5 cm2/V.s.