Miracle-dz/UniFAR-FTUs huggingface dataset:
BACE1 Inhibition Induces a Specific Cerebrospinal Fluid β-Amyloid Pattern That Identifies Drug Effects in the Central Nervous System

BACE1 is a key enzyme for amyloid-β (Aβ) production, and an attractive therapeutic target in Alzheimer's disease (AD). Here we report that BACE1 inhibitors have distinct effects on neuronal Aβ metabolism, inducing a unique pattern of secreted Aβ peptides, analyzed in cell media from amyloid precursor protein (APP) transfected cells and in cerebrospinal fluid (CSF) from dogs by immunoprecipitation-mass spectrometry, using several different BACE1 inhibitors. Besides the expected reductions in Aβ1-40 and Aβ1-42, treatment also changed the relative levels of several other Aβ isoforms. In particular Aβ1-34 decreased, while Aβ5-40 increased, and these changes were more sensitive to BACE1 inhibition than the changes in Aβ1-40 and Aβ1-42. The effects on Aβ5-40 indicate the presence of a BACE1 independent pathway of APP degradation. The described CSF Aβ pattern may be used as a pharmacodynamic fingerprint to detect biochemical effects of BACE1-therapies in clinical trials, which might accelerate development of novel therapies.
Scrubs and Squatters: The Coming of the Dukuduku Forest, an Indigenous Forest in KwaZulu-Natal, South Africa

Against the backdrop of current demands of historical redress and restitution of land in KwaZulu-Natal, South Africa, this article provides a historical analysis of landscape change and changing ideas about nature in relation to the Dukuduku forest. From the time of the first written sources in the mid-nineteenth century up until the point when the forest turned into an informal settlement area in the 1990s, people have used and perceived the forest. Dukuduku's image as a pristine indigenous forest is problematic, for it obscures local lives and histories. Inhabitation of the Dukuduku forest is not a recent phenomenon. Colonial preservation measures have little continuity with present-day environmentalism. The article demonstrates the incompleteness of a wilderness vision of nature in which humans intervene by utilitarian motives or conservation visions.
Bidirectionalizing graph transformations

Bidirectional transformations provide a novel mechanism for synchronizing and maintaining the consistency of information between input and output. Despite many promising results on bidirectional transformations, these have been limited to the context of relational or XML (tree-like) databases. We challenge the problem of bidirectional transformations within the context of graphs, by proposing a formal definition of a well-behaved bidirectional semantics for UnCAL, i.e., a graph algebra for the known UnQL graph query language. The key to our successful formalization is full utilization of both the recursive and bulk semantics of structural recursion on graphs. We carefully refine the existing forward evaluation of structural recursion so that it can produce sufficient trace information for later backward evaluation. We use the trace information for backward evaluation to reflect in-place updates and deletions on the view to the source, and adopt the universal resolving algorithm for inverse computation and the narrowing technique to tackle the difficult problem with insertion. We prove our bidirectional evaluation is well-behaved. Our current implementation is available online and confirms the usefulness of our approach with nontrivial applications.
RADAR SIGNALS

Description: A text and general reference on the design and analysis of radar signals As radar technology evolves to encompass a growing spectrum of applications in military, aerospace, automotive, and other sectors, innovations in digital signal processing have risen to meet the demand. Presenting a long overdue, up–to–date, dedicated resource on radar signals, the authors fill a critical gap in radar technology literature. Radar Signals features in–depth coverage of the most prevalent classical and modern radar signals used today, as well as new signal concepts developed in recent years. Inclusion of key MATLAB software codes throughout the book demonstrates how they dramatically simplify the process of describing and analyzing complex signals. Topics covered include:-Matched filter and ambiguity function concepts-Basic radar signals, with both analytical and numerical analysis-Frequency modulated and phase–coded pulses-Complete discussion of band–limiting schemes-Coherent LFM pulse trains the most popular radar signal-Diversity in pulse trains, including stepped frequency pulses-Continuous–wave signals-Multicarrier phase–coded signals Combining lucid explanation, preferred signal tables, MATLAB codes, and problem sets in each chapter, Radar Signals is an essential reference for professionals and a systematic tutorial for any seeking to broaden their knowledge base in this dynamic field.
A specific role for the C-terminal region of the Poly(A)-binding protein in mRNA decay

mRNA poly(A) tails affect translation, mRNA export and mRNA stability, with translation initiation involving a direct interaction between eIF4G and the poly(A)-binding protein Pab1. The latter factor contains four RNA recognition motifs followed by a C-terminal region composed of a linker and a PABC domain. We show here that yeast mutants lacking the C-terminal domains of Pab1 display specific synthetic interactions with mutants in the 5′-3′ mRNA decay pathway. Moreover, these mutations impair mRNA decay in vivo without significantly affecting mRNA export or translation. Inhibition of mRNA decay occurs through slowed deadenylation. In vitro analyses demonstrate that removal of the Pab1 linker domain directly interferes with the ability of the Pop2–Ccr4 complex to deadenylate the Pab1-bound poly(A). Binding assays demonstrate that this results from a modulation of poly(A) packaging by the Pab1 linker region. Overall, our results demonstrate a direct involvement of Pab1 in mRNA decay and reveal the modular nature of this factor, with different domains affecting various cellular processes. These data suggest new models involving the modulation of poly(A) packaging by Pab1 to control mRNA decay.
Evidence that the renin decrease during hypoxia is adenosine mediated in conscious dogs.

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol.kg body wt(-1). day(-1)). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O(2)); second and third hours, hypoxia (10% inspiratory concentration of O(2)). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A(1)-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg. kg(-1). h(-1)). In theophylline experiments, PRA (5.9 +/- 0.8 ng ANG I. ml(-1). h(-1)) and ANG II plasma concentration (15.9 +/- 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 +/- 63 to 132 +/- 23 pg/ml (P < 0.05). In control experiments, PRA decreased from 6.8 +/- 0.8 during normoxia to 3.0 +/- 0.5 ng ANG I. ml(-1). h(-1) during hypoxia, ANG II decreased from 13.3 +/- 1.9 to 7.3 +/- 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 +/- 50 to 70 +/- 13 pg/ml (P < 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.
Assessing Influence on the Field: An Analysis of Citations to Educational Administration Quarterly, 1979—2003

Study Purpose: This article examines the influence of Educational Administration Quarterly (EAQ) on the scholarly literature in education during the 25-year period 1979 to 2003. This article continues part of the first critique of EAQ conducted by Roald Campbell in 1979. Study Methods: Two citation measures are used in this study to assess EAQ influence: (a) citation frequency, the total citations counts to EAQ articles found in the Web of Science database and (b) the impact factor, a ratio of citations to articles published that is calculated as part of the Journal Citation Reports. Study Findings: The findings point to three conclusions: (a) EAQ's substantive, ongoing influence on the scholarly education literature is limited to a small percentage of its published articles, which are cited predominantly by subsequent articles in EAQ; (b) this level of influence, though perhaps not the form, appears to be generally comparable to the level of other scholarly education journals with a solid academic reputation; and (c) EAQ appears to be statistically among the top tier of influential scholarly journals in education, but below the most influential. Overall, EAQ's influence on the scholarly education literature has improved since the first critique published in 1979.
Dendritic cell dysregulation during HIV‐1 infection

Dendritic cells (DCs) are a diverse subset of innate immune cells that are key regulators of the host response to human immunodeficiency virus‐1 (HIV‐1) infection. HIV‐1 directly and indirectly modulates DC function to hinder the formation of effective antiviral immunity and fuel immune activation. This review focuses upon the differential dysregulation of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) at various stages of HIV‐1 infection providing insights into pathogenesis. HIV‐1 evades innate immune sensing by mDCs resulting in suboptimal maturation, lending to poor generation of antiviral adaptive responses and contributing to T‐regulatory cell (Treg) development. Dependent upon the stage of HIV‐1 infection, mDC function is altered in response to Toll‐like receptor ligands, which further hinders adaptive immunity and limits feasibility of therapeutic vaccine strategies. pDC interactions with HIV‐1 are pleotropic, modulating immune responses on an axis between immunostimulatory and immunosuppressive. pDCs promote immune activation through an altered phenotype of persistent type I interferon secretion and weak antigen presentation capacity. Conversely, HIV‐1 stimulates secretion of indolemine 2,3 dioxygenase (IDO) by pDCs resulting in Treg induction. An improved understanding of the roles and underlying mechanisms of DC dysfunction will be valuable to the development of therapeutics to enhance HIV‐specific adaptive responses and to dampen immune activation.
Identification of secretin , vasoactive intestinal peptide and glucagon binding sites : from chimaeric receptors to point mutations

We have identified two basic residues that are important for the recognition of secretin and vasoactive intestinal peptide (VIP) by their respective receptors. These two peptides containing an Asp residue at position 3 interacted with an arginine residue in transmembrane helix 2 (TM2) of the receptor, and the lysine residue in extracellular loop 1 (ECL1) stabilized the active receptor conformation induced by the ligand. The glucagon receptor possesses a Lys instead of an Arg in TM2, and an Ile instead of Lys in ECLl ; it markedly prefers a Gln side chain in position 3 of the ligand. Our results suggested that, in the wild-type receptor, the Ile side chain prevented access to the TM2 Lys side chain, but oriented the glucagon Gln3 side chain to its proper binding site. In the double mutant, the ECLl Lys allowed an interaction between negatively charged residues in position 3 of glucagon and the TM2 Arg, resulting in efficient receptor activation by [Asp3]glucagon as well as by glucagon.
Depathologizing the tourist syndrome

The intention of this article is to discuss and contrast two central aspects of a published interview with Zygmunt Bauman addressing the nature of `the tourist syndrome' (Franklin, 2003). First, the tourist syndrome is a metaphor for contemporary living in liquid modernity and second, tourism is referred to as `a substitute satisfaction of a genuine need' (Franklin, 2003: 214). The interview presents a critical and somewhat sceptical perspective on tourism and social life, in which the tourist syndrome is labelled a `peg community' and the tourism industry characterized as an insatiable seducer. Based on the experiences of Norwegian midlife single women, a more positive notion is suggested. Although most of the midlife single women do not seek difference as tourists, the meaning of tourism is not superficial and/or contrived. It is rather a space for bonding with significant others and about social integration in everyday life.
Relationship of LDL size to insulin sensitivity in normoglycemic men.

A preponderance of small, dense LDL has been suggested to be more atherogenic than larger, more buoyant LDL. Although several studies have suggested associations of small, dense LDL with hyperinsulinemia, few data are available on the relation of small, dense LDL to insulin resistance. We examined the association of LDL particle size determined by gradient gel electrophoresis with the rates of whole-body glucose uptake (WBGU) as determined by the hyperinsulinemic euglycemic clamp with indirect calorimetry in 87 Finnish normoglycemic men. LDL size was significantly positively correlated with the rates of WBGU (overall, r = .31, P < .01; oxidative, r = .23, P < .05; and nonoxidative, r = .31, P < .01). Rates of WBGU were also significantly lower in subjects with small LDL particles (< or = 26.0 nm) compared with those in subjects with larger LDL particles (> 26.0 nm). This relation was not explained by obesity. Serum triglyceride concentrations were found to significantly affect the relationship of LDL particle size to WBGU. Specifically, LDL size was correlated with the rates of WBGU in men with mildly elevated triglyceride levels but not in men with low triglyceride levels. Serum VLDL triglyceride concentration was a substantially stronger determinant of LDL size than were the rates of WBGU. WBGU was not significantly related to LDL size when adjusted for triglycerides. We conclude that a preponderance of small, dense LDL particles is associated with insulin resistance and that serum triglyceride concentration modifies this relationship.
Can inorganic phosphate explain sag during unfused tetanic contractions of skeletal muscle?

We test the hypothesis that cytosolic inorganic phosphate (Pi) can account for the contraction‐induced reductions in twitch duration which impair summation and cause force to decline (sag) during unfused tetanic contractions of fast‐twitch muscle. A five‐state model of crossbridge cycling was used to simulate twitch and unfused tetanic contractions. As Pi concentration ([Pi]) was increased from 0 to 30 mmol·L−1, twitch duration decreased, with progressive reductions in sensitivity to Pi as [Pi] was increased. When unfused tetani were simulated with rising [Pi], sag was most pronounced when initial [Pi] was low, and when the magnitude of [Pi] increase was large. Fast‐twitch extensor digitorum longus (EDL) muscles (sag‐prone, typically low basal [Pi]) and slow‐twitch soleus muscles (sag‐resistant, typically high basal [Pi]) were isolated from 14 female C57BL/6 mice. Muscles were sequentially incubated in solutions containing either glucose or pyruvate to create typical and low Pi environments, respectively. Twitch duration was greater (P < 0.05) in pyruvate than glucose in both muscles. Stimuli applied at intervals approximately three times the time to peak twitch tension resulted in sag of 35.0 ± 3.7% in glucose and 50.5 ± 1.4% in pyruvate in the EDL (pyruvate > glucose; P < 0.05), and 3.9 ± 0.3% in glucose and 37.8 ± 2.7% in pyruvate in the soleus (pyruvate > glucose; P < 0.05). The influence of Pi on crossbridge cycling provides a tenable mechanism for sag. Moreover, the low basal [Pi] in fast‐twitch relative to slow‐twitch muscle has promise as an explanation for the fiber‐type dependency of sag.
Working Group on Development and Environment in the Americas Discussion Paper Number 3 Trade , Environment and Development : The Recent Argentine Experience

The Working Group on Development and Environment in the Americas, founded in 2004, brings together economic researchers from several countries in the Americas who have carried out empirical studies of the social and environmental impacts of economic liberalization. The Working Group's goal is to contribute empirical research and policy analysis to the ongoing policy debates on national economic development strategies and international trade. The Working Group held its inaugural meeting in Brasilia, March 29-30, 2004. This paper is one of eight written for the Brasilia meetings. They are the basis for " Globalization and the Environment: Lessons from the Americas, " a policy report published by the Heinrich Böll Foundation in July 2004. Daniel Chudnovsky is an Argentine economist who is professor at the University of San Andrés and Director of the Centro de Investigaciones para la Transformación (CENIT) in Buenos Aires. He worked for several years in the Technology Division of UNCTAD in Geneva and was the first Director of the Centro de Economía Internacional in Buenos Aires. He has published widely on trade, industrial restructuring, foreign direct investment, regional integration, environment and technology issues, mostly in relation to Latin America. Web page:
Avant les croyances

Il est suggere avec de plus en plus d'insistance que les interactions et les conversations en triades sociales, adulte-adulte-enfant ou Adulte- Enfant- Enfant, jouent un role determinant dans l'acquisition d'une theorie de l'esprit pendant les premieres annees de la vie. En revanche, peu d'etudes ont examine l'emergence des conduites liees a l'attention conjointe a propos des personnes en triade sociale, alors que celles tournees vers un objet au sein d'une dyade sont considerees actuellement comme un precurseur metarepresentationnel privilegie. Le premier objectif de cet article est de considerer l'originalite et la specificite des capacites a suivre l'orientation du regard, de faire des va-et-vient du regard, et de produire des emissions sociales quand elles concernent exclusivement les personnes en situation sociale triadique adulte-adulte-enfant. Le second objectif est de montrer qu 'une situation de communication a trois, controlee par le paradigme de l'exclusion, induit des 3 mois la mise en œuvre synchronique de ces trois competences et participe a l'emergence de la connaissance des etres humains comme ayant des perceptions, des desirs et des intentions.
In Vivo Uptake of [3H]Nimodipine in Focal Cerebral Ischemia: Modulation by Hyperglycemia

Cell membrane depolarization and tissue acidosis occur rapidly in severely ischemic brain. Preischemic hyperglycemia is recognized to increase ischemic tissue acidosis and the present studies were undertaken to correlate depolarization and tissue acidosis during acute focal cerebral ischemia and hyperglycemia. We used a dual-label autoradiography method to simultaneously measure the in vivo distribution of [3H]nimodipine and [14C]DMO (5,5-dimethyl-2,4-oxazolidinedione) in brain to identify regions of ischemic depolarization and measure regional net tissue pH. Regional cerebral blood flow (CBF) was measured in separate studies. Measurements were made 30 minutes after combined middle cerebral artery and ipsilateral common carotid artery occlusion in normoglycemic and hyperglycemic rats. Tissue pH in the ischemic cortex was depressed to 6.76 ± 0.11 in normoglycemic rats (n = 12) and 6.57 ± 0.13 in hyperglycemic rats (n = 12), with significantly greater acidosis in the hyperglycemic group (P < 0.001). In contrast the ratio of [3H]nimodipine uptake in the ischemic cortex relative to the contralateral nonischemic cortex was significantly greater in normoglycemic (1.83 ± 0.45) than hyperglycemic (1.40 ± 0.50) rats (P < 0.05). Within this region of ischemic cortex CBF was 31 ± 22 mL/100 g in normoglycemic rats (n = 8) and 33 ± 22 mL/100 g/min in hyperglycemic rats (n = 9). Cerebral blood flow did not differ between these two groups in any region. Thus hyperglycemia reduced the extent of ischemic depolarization within the cortex during the first 30 minutes of focal cerebral ischemia. This effect may be related to the increased tissue acidosis or to other factors that may lessen calcium influx and preserve cellular energy stores in the ischemic cortex of the hyperglycemic rats.
E-SIA : un système d'annotation et de recherche de documents audiovisuels

L'annotation et la recherche de documents audiovisuels sont des tâches complexes. Dans ce papier nous presentons un modele d'organisation des annotations dans un graphe connexe oriente etiquete ainsi que des methodes de recherche et d'exploration basees sur cette structure. Le graphe contient aussi bien les annotations elles-memes que le vocabulaire utilise pour annoter, des elements qui permettent de structurer ce vocabulaire et des representants des fragments de documents annotes. Nous decrivons egalement le prototype client serveur developpe dans le cadre d'un projet RNRT en partenariat avec France Telecom R&D et INRIA pour demontrer la faisabilite de nos theories.
Enhancing evolutionary multifactorial optimization based on particle swarm optimization

Multifactorial evolutionary algorithm is used to deal with multifactorial optimization problem which simultaneously optimizes multiple tasks. In this paper, we introduce particle swarm optimization operation into the multifactorial evolutionary algorithm, and propose a hybrid algorithm for multifactorial optimization. The major aim is to utilize particle swarm optimization operation to accelerate the convergence and improve the accuracy of solutions. Experimental comparisons between the proposed hybrid algorithm and the original multi-factorial evolutionary algorithm show that the particle swarm update operators can effectively accelerate the convergence on some benchmark problems.
Subunit conformational variation within individual GroEL oligomers resolved by Cryo-EM

Significance Using cryo-EM and expanding on focused classification allowed for the bacterial chaperone, GroEL, to be structurally resolved at atomic detail one particle at a time. This approach differs from generating the traditional structural ensemble average of presumably identical particle images. Three dominant subunit conformations were identified, and their spatial distributions were found to be different in each individual GroEL oligomer. This strategy demonstrates the application of cryo-EM to characterize the biophysical properties of structural dynamics of individual molecular machines one at a time. Single-particle electron cryo-microscopy (cryo-EM) is an emerging tool for resolving structures of conformationally heterogeneous particles; however, each structure is derived from an average of many particles with presumed identical conformations. We used a 3.5-Å cryo-EM reconstruction with imposed D7 symmetry to further analyze structural heterogeneity among chemically identical subunits in each GroEL oligomer. Focused classification of the 14 subunits in each oligomer revealed three dominant classes of subunit conformations. Each class resembled a distinct GroEL crystal structure in the Protein Data Bank. The conformational differences stem from the orientations of the apical domain. We mapped each conformation class to its subunit locations within each GroEL oligomer in our dataset. The spatial distributions of each conformation class differed among oligomers, and most oligomers contained 10–12 subunits of the three dominant conformation classes. Adjacent subunits were found to more likely assume the same conformation class, suggesting correlation among subunits in the oligomer. This study demonstrates the utility of cryo-EM in revealing structure dynamics within a single protein oligomer.