Miracle-dz/UniFAR-FTUs huggingface dataset:
ZnT‐1 expression in astroglial cells protects against zinc toxicity and slows the accumulation of intracellular zinc

Zinc ions are emerging as an important factor in the etiology of neurodegenerative disorders and in brain damage resulting from ischemia or seizure activity. High intracellular levels of zinc are toxic not only to neurons but also to astrocytes, the major population of glial cells in the brain. In the present study, the role of ZnT‐1 in reducing zinc‐dependent cell damage in astrocytes was assessed. Zinc‐dependent cell damage was apparent within 2 h of exposure to zinc, and occurred within a narrow range of ∼200 μM. Pretreatment with sublethal concentrations of zinc rendered astrocytes less sensitive to toxic zinc levels, indicating that preconditioning protects astrocytes from zinc toxicity. Fluorescence cell imaging revealed a steep reduction in intracellular zinc accumulation for the zinc‐pretreated cells mediated by L‐type calcium channels. Heterologous expression of ZnT‐1 had similar effects; intracellular zinc accumulation was slowed down and the sensitivity of astrocytes to toxic zinc levels was reduced, indicating that this is specifically mediated by ZnT‐1 expression. Immunohistochemical analysis demonstrated endogenous ZnT‐1 expression in cultured astroglia, microglia, and oligodendrocytes. Pretreatment with zinc induced a 4‐fold increase in the expression of the putative zinc transporter ZnT‐1 in astroglia as shown by immunoblot analysis. The elevated ZnT‐1 expression following zinc priming or after heterologous expression of ZnT‐1 may explain the reduced zinc accumulation and the subsequent reduction in sensitivity toward toxic zinc levels. Induction of ZnT‐1 may play a protective role when mild episodes of stroke or seizures are followed by a massive brain insult. © 2004 Wiley‐Liss, Inc.
Automatic semantic annotation using unsupervised information extraction and integration

In this paper we propose a methodology to learn to automatically annotate domain-specific information from large repositories (e.g. Web sites) with minimum user intervention. The methodology is based on a combination of information extraction, information integration and machine learning techniques. Learning is seeded by extracting information from structured sources (e.g. databases and digital libraries). Retrieved information is then used to partially annotate documents. These annotated documents are used to bootstrap learning for simple Information Extraction (IE) methodologies, which in turn will produce more annotations used to annotate more documents. It will be used to train more complex IE engines and the cycle will keep on repeating itself until the required information is obtained. The user intervention is limited to providing an initial URL and to correct information if it is the case when the computation is finished. The revised annotation can then be reused to provide further training and therefore getting more information and/or more precision.
Splitting for Rare-event Simulation

Splitting and importance sampling are the two primary techniques to make important rare events happen more frequently in a simulation, and obtain an unbiased estimator with much smaller variance than the standard Monte Carlo estimator. Importance sampling has been discussed and studied in several articles presented at the Winter Simulation Conference in the past. A smaller number of WSC articles have examined splitting. In this paper, we review the splitting technique and discuss some of its strengths and limitations from the practical viewpoint. We also introduce improvements in the implementation of the multilevel splitting technique. This is done in a setting where we want to estimate the probability of reaching B before reaching (or returning to) A when starting from a fixed state x 0 ∈ B, where A and B are two disjoint subsets of the state space and B is very rarely attained. This problem has several practical applications. 1 SETTING We consider a discrete-time Markov chain {X j , j ≥ 0} with state space X. Let A and B be two disjoint subsets of X and let x 0 ∈ X \ B be the initial state. The chain starts in state X 0 = x 0 , leaves the set A if x 0 ∈ A, and then eventually reaches B or A. Let τ A = inf{ j > 0 : X j−1 ∈ A and X j ∈ A}, the first time when the chain hits A (or returns to A after leaving it), and τ B = inf{ j > 0 : X j ∈ B}, the first time when the chain reaches the set B. The goal is to estimate γ = P[τ B < τ A ], the probability that the chain reaches B before A. This particular form of rare-event problem, where γ is small, occurs in many practical situations (Shahabuddin 1994, Heidelberger 1995). The standard Monte Carlo method estimates γ by running n independent copies of the chain up to the stopping time τ = min(τ A , τ B), and counting the proportion of runs for which the event {τ B
Autoradiographic localization of specifically bound 125I-labeled follicle-stimulating hormone on spermatogonia of the rat testis.

In a previous study, we used autoradiography to demonstrate specific FSH-binding sites on Sertoli plasma membranes in the basal compartment of rat seminiferous tubules. The present study was undertaken to determine whether spermatogonia in the rat testis also possess FSH-binding sites. Approximately 1 Mg [l25I]hFSH was administered as an intratesticular injection to 40-day-old rats that had been hypophysectomized 10 days earlier; a second group of rats received a 500-fold excess of cold hormone along with the [I25I]- hFSH, and served as a control for specificity of binding. Subsequently, all testes were perfused with a hyperosmotic fixative, which produces preferential shrinkage of spermatogonia and Sertoli cells in the basal compartment. The resulting separation of the cells from one another allowed us to determine whether spermatogonia were the source of any autoradiographic grains. In the absence of excess cold hormone, some grains were clearly localized to spermatogonial surfaces, although the majorit.
The design and evaluation of selection techniques for 3D volumetric displays

Volumetric displays, which display imagery in true 3D space, are a promising platform for the display and manipulation of 3D data. To fully leverage their capabilities, appropriate user interfaces and interaction techniques must be designed. In this paper, we explore 3D selection techniques for volumetric displays. In a first experiment, we find a ray cursor to be superior to a 3D point cursor in a single target environment. To address the difficulties associated with dense target environments we design four new ray cursor techniques which provide disambiguation mechanisms for multiple intersected targets. Our techniques showed varied success in a second, dense target experiment. One of the new techniques, the depth ray, performed particularly well, significantly reducing movement time, error rate, and input device footprint in comparison to the 3D point cursor.
Chromosomal reinsertion of broken RSS ends during T cell development

The V(D)J recombinase catalyzes DNA transposition and translocation both in vitro and in vivo. Because lymphoid malignancies contain chromosomal translocations involving antigen receptor and protooncogene loci, it is critical to understand the types of “mistakes” made by the recombinase. Using a newly devised assay, we characterized 48 unique TCRβ recombination signal sequence (RSS) end insertions in murine thymocyte and splenocyte genomic DNA samples. Nearly half of these events targeted “cryptic” RSS-like elements. In no instance did we detect target-site duplications, which is a hallmark of recombinase-mediated transposition in vitro. Rather, these insertions were most likely caused by either V(D)J recombination between a bona fide RSS and a cryptic RSS or the insertion of signal circles into chromosomal loci via a V(D)J recombination-like mechanism. Although wild-type, p53, p53 x scid, H2Ax, and ATM mutant thymocytes all showed similar levels of RSS end insertions, core-RAG2 mutant thymocytes showed a sevenfold greater frequency of such events. Thus, the noncore domain of RAG2 serves to limit the extent to which the integrity of the genome is threatened by mistargeting of V(D)J recombination.
Leprosy and Human Immunodeficiency Virus Infection

A woman visited our venereal disease outpatient clinic to be tested for HIV infection. Sbe bad been working as a prostitute on tbe Soutb American mainland, tbe Caribbean, and in New York City. Sbe bad never used intravenous drugs. Her medical bistory revealed tbat sbe had a hepatitis B infection in 1978 and primary syphilis in 1984 for wbich she had been treated. Besides general symptoms of weight loss and anorexia, she had recently developed an anesthetic skin lesion on her right upper arm. Upon dermatologic examination, a hypopigmented macule of 6-7 cm in diameter with a minimal elevated slightly erythematous border was observed on her right upper arm. The sensitivity to light touch in tbe center of this lesion was clearly diminished as compared to tbat of the surrounding skin. A small hypopigmented macule with normal sensation was also seen on tbe abdomen. Peripheral nerves were not enlarged and there were no signs of peripheral neuropathy. Clinically, the lesions were compatible witb borderline tuberculoid-mid borderline (BT/BB) leprosy. Histologic examination of the biopsy specimens taken from the lesion on the upper arm showed perivascular and perineural lymphohistiocytic infiltrations with a tendency to granuloma formation. In and around the granuloma a mild extracellular edema was seen. Some of the histiocytes bad foamy cytoplasm and in a Wade-Fite's stained preparation contained solid staining acid-fast bacteria. The same histologic features, but with markedly less lymphocytic infiltrate, were observed in tbe specimen from the lesion of the abdomen. Tbe bistopathology was that of a borderline lepromatous (BL) leprosy in reaction. Immunobistochemical studies of the biopsy specimens showed that HLA-Dr was not expressed on the keratinocytes in the epidermis. There was a decrease in the number of Langerhans cells in tbe epidermis. The granulomas consisted of 75% T lymphocytes (CD3-Icells) and 25% histiocytes. The lympbocytic infiltrate consisted of 50% CD4-f and 30 to 40% CD8-Icells. No interleukin-2 (IL-2) receptor positive cells or natural killer (NK) cells were present in the infiltrate.
Alpha‐Synuclein induces hyperphosphorylation of Tau in the MPTP model of Parkinsonism

Many neurodegenerative diseases associated with functional Tau dysregulation, including Alzheimer's disease (AD) and other tauopathies, also show α‐synuclein (α‐Syn) pathology, a protein associated with Parkinson's disease (PD) pathology. Here we show that treatment of primary mesencephalic neurons (48 h) or subchronic treatment of wild‐type (WT) mice with the Parkinsonism‐inducing neurotoxin MPP+/MPTP, results in selective dose‐dependent hyperphosphorylation of Tau at Ser396/404 (PHF‐1‐reactive Tau, p‐Tau), with no changes in pSer202 but with nonspecific increases in pSer262 levels. The presence of α‐Syn was absolutely mandatory to observe MPP+/MPTP‐induced increases in p‐Tau levels, since no alterations in p‐Tau were seen in transfected cells not expressing α‐Syn or in α‐Syn‐/‐ mice. MPP+/MPTP also induced a significant accumulation of α‐Syn in both mesencephalic neurons and in WT mice striatum. MPTP/MPP+ lead to differential alterations in p‐Tau and α‐Syn levels in a cytoskeleton‐bound, vs. a soluble, cytoskeleton‐free fraction, inducing their coimmunoprecipitation in the cytoskeleton‐free fraction and neuronal soma. Subchronic MPTP exposure increased sarkosyl‐insoluble p‐Tau in striatum of WT but not α‐Syn‐/‐ mice. These studies describe a novel mechanism for MPTP neurotoxicity, namely a MPTP‐inducible, strictly α‐Syn‐dependent, increased formation of PHF‐1‐reactive Tau, suggesting convergent overlapping pathways in the genesis of clinically divergent diseases such as AD and PD. —Duka, T. , Rusnak, M. , Drolet, R. E. , Duka, V. , Wersinger, C. , Goudreau, J. L. , Sidhu, A. Alpha‐synuclein induces hyperphosphorylation of Tau in the MPTP model of Parkinsonism. FASEB J. 20, 2302–2312 (2006)
The Linear Interaction Model of Personality Effects in Health Communication

The recent growth of research in message tailoring has opened up new avenues for researchers to use personality variables for message delivery. This article builds on research on idiocentrism and self-monitoring to propose a framework for message appeal construction. Based on a scheme for appeal categorization borrowed from commercial marketing, the article suggests that low and high idiocentrics differ from each other in the way they respond to appeal types. Similarly, significant differences are demonstrated between low and high self-monitors in the realm of their response to message appeals. A linear interaction model is proposed to document the combined effects of self-monitoring and idiocentrism.
The domestic productivity effects of FDI in Greece: loca(lisa)tion matters!

Despite an extensive empirical literature on the factors conditioning the size and prevalence of FDI productivity spillovers, the geographical dimension of these externalities remains relatively under-explored. In this paper we use firm level data from the Greek manufacturing sector to identify how three features of economic geography – spatial heterogeneity (location), spatial proximity (localisation) and spatial concentration (agglomeration) – influence the size and sign of FDI spillovers within and across industries. We find that FDI spillovers predominantly materialise at the sub-national level, with horizontal spillovers being more prominent at the regional scale (NUTS2) and vertical spillovers being highly localised (at the NUTS3 level). Furthermore, we find important synergies between spillovers from FDI and industry-region specific agglomeration. Also, FDI spillovers are found to be conditional on regional characteristics related to each region’s manufacturing base, FDI concentration, urban agglomeration and aggregate productivity. These results highlight the important role played by geography for the materialisation of productivity spillovers accruing from FDI and suggest that these key geographical features (location, localisation and agglomeration) ought to be taken into account both in the study of FDI spillovers and in the design of FDI-promotion and regional development policies.
Acaricidal activities of whole cell suspension, cell-free supernatant, and crude cell extract of Xenorhabdus stokiae against mushroom mite (Luciaphorus sp.)

Xenorhabdus bacterium has been used as a biological control agent against Luciaphorus sp. , a mushroom mite endemic in Thailand. To develop an effective formulation of Xenorhabdus stokiae, treatments using different parts of X. stokiae isolate PB09 culture, including whole cell suspension, cell-free supernatant, and crude cell extract, were performed. The results show that different parts of X. stokiae isolate PB09 culture could induce variable effects on mite mortality and fecundity. Application with cell-free supernatant of X. stokiae culture resulted in both the highest mite mortality rate [(89.00±3.60)%] and the lowest mite fecundity [(41.33±23.69) eggs/gravid female]. Whole cell suspension of X. stokiae isolate PB09 culture was found to be slightly less effective than its cell-free supernatant, suggesting that X. stokiae was more likely to release its metabolites with acaricidal activities to the surrounding culture media. Crude cell extract of X. stokiae was not effective against mites. Cell-free supernatant of X. stokiae isolate PB09 was the most effective biological control agent and it could be conveniently used in future formulations instead of live bacteria.
Analysis of the solar cycle and core rotation using 15 years of Mark-I observations: 1984-1999 - I. The solar cycle

High quality observations of the low-degree acoustic modes ( p -modes) exist for almost two complete solar cycles using the solar spectrophotometer Mark-I, located at the Observatorio del Teide (Tenerife, Spain) and operating now as part of the Birmingham Solar Oscillations Network (BiSON). We have performed a Fourier analysis of 30 calibrated time-series of one year duration covering a total period of 15 years between 1984 and 1999. Applying different techniques to the resulting power spectra, we study the signature of the solar activity changes on the low-degree p -modes. We show that the variation of the central frequencies and the total velocity power ( TVP ) changes. A new method of simultaneous fit is developed and a special effort has been made to study the frequency-dependence of the frequency shift. The results confirm a variation of the central frequencies of acoustic modes of about 0.45 μ Hz, peak-to-peak, on average for low degree modes between 2.5 and 3.7 mHz. The TVP is anti-correlated with the common activity indices with a decrease of about 20% between the minimum and the maximum of solar cycle 22. The results are compared with those obtained for intermediate degrees, using the LOWL data. The frequency shift is found to increase with the degree with a weak $\ell$-dependence similar to that of the inverse mode mass. This verifies earlier suggestions that near surface effects are predominant.
Chapter 18 Volatility Transmission across Commodity Futures Markets

The recent sharp movements in crude oil prices and their impact on other commodities have renewed interest in the assessment of dynamic interactions between commodity futures markets. This chapter examines this important topic by investigating the intensity and direction of volatility transmission across three major classes of commodities including agricultural products (corn, coffee, and soybeans), energy (crude oil and gas), and metals (copper, gold, and silver). Overall, the evidence suggests that important volatility episodes and fluctuations exist across major commodity markets; the total cross-market spillovers are limited until the onset of financial crisis of 2007-2008. As the crisis intensified, so too did the commodity volatility spillovers with substantial stress carrying over from the energy and metal markets to others. These findings are important in understanding the level and transmission mechanism of risk across commodity futures markets and are relevance to regulators in formulating effective policies to tackle excessive volatility, particularly during turbulent periods.
Are Infants Discriminatory Learners and Helpers? The Influence of a Model’s Reliability on Infants’ Selective Trust

The objective of the present dissertation was to examine infants’ selective trust as influenced by different aspects of a model’s reliability. The first study examined whether eighteen-month-old infants would behave differently towards a speaker as a function of how accurately she labeled familiar objects. The behavioral markers of trust examined were whether infants learned a novel word, imitated the speaker’s irrational actions, and helped the speaker obtain an out-of-reach object. In contrast to infants exposed to an accurate speaker, those who interacted with an inaccurate speaker performed more poorly on a word learning task and were less likely to imitate. All infants demonstrated high rates of instrumental helping. The second study aimed to tease apart the effects of a model’s intent (benevolence or malevolence) and verbal competence (knowledge or ignorance of familiar object labels) on 18-month-olds’ selective trust when both factors were simultaneously presented but independently manipulated. Infants’ non-verbal behaviors indicated that they became impatient with the malevolent experimenter. Infants also, though more modestly, modified their selective learning; while they were less likely to learn a novel word from either an ignorant and malevolent model, they were more likely to imitate the competent but malevolent model. In addition, while none of the infants modified their strong willingness to help, all infants tended to look longer at a neutral image of the experimenter in comparison to that of a stranger. Finally, the third study examined how 24-month-olds’ selective trust would be affected by the emotional reliability of a familiar model, such as the level of sensitivity of a primary caregiver (coded during a 10-min period of interaction between the dyad). Infants learned novel words better from an emotionally reliable primary caregiver. In addition, higher parental responsiveness and availability predicted better imitation in older children and higher levels of helping in girls. Taken together, these findings are the first to demonstrate that infants consider a model’s verbal, intentional, and emotional reliability when deciding whether to learn but not when deciding to help. Thus, infants’ selective trust appears to be motivated by epistemic and emotional factors.
Time-reversal imaging with multiple signal classification considering multiple scattering between the targets

The time-reversal imaging with multiple signal classification method for the location of point targets developed within the framework of the Born approximation in Lehman and Devaney [“Transmission mode time-reversal super-resolution imaging,” J. Acoust. Soc. Am. 113, 2742–2753 (2003)] is generalized to incorporate multiple scattering between the targets. It is shown how the same method can be used in the location of point targets even if there is multiple scattering between them. On the other hand, both the conventional images and the calculated values of the target scattering amplitudes are scattering model-dependent.
An Open-Label, Sequential Dose-Escalation, Safety, and Tolerability Study of Rimabotulinumtoxinb in Subjects With Cervical Dystonia

ABSTRACT Objectives: Evaluate the safety and efficacy of a sequential dose escalation of rimabotulinumtoxinB (BoNT-B) in cervical dystonia (CD) subjects. Methods: This multicenter, open-label, within-subject, sequential dose-escalation study (BoNT-B dosed at 10,000, 12,500, and 15,000 Units) evaluated subjects over each phase of treatment at preinjection and at periodic intervals postinjection. Adverse events, vital signs, and laboratory results were recorded. Efficacy measures included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and three visual analog scales (VASs). Results: 119 out of 145 CD subjects received all three doses in sequence. Dry mouth and dysphagia were the most common adverse events, and both decreased in frequency by the final injection, despite the increasing doses of the escalation. TWSTRS-Total and subscale scores demonstrated significant improvements following all doses at the week 2, 4, 8, and 12 assessments, with the exception of disability and pain at week 12 with the lowest dose. All VAS scores demonstrated similar improvements following all doses. The mean number of weeks in each phase of the study was 12.1 weeks (10,000 Units), 12.9 weeks (12,500 Units), and 13.9 weeks (15,000 Units). Conclusion: BoNT-B was well tolerated and efficacious at 10,000, 12,500, and 15,000 Units in this within-subject, sequential dose-escalation study in CD subjects.