Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunocytochemical Characterization of Alzheimer Disease Hallmarks in APP/PS1 Transgenic Mice Treated with a New Anti-Amyloid-β Vaccine

APP/PS1 double-transgenic mouse models of Alzheimer's disease (AD), which overexpress mutated forms of the gene for human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of AD-like pattern at early ages. This study characterizes immunocytochemical patterns of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this novel vaccine, a new approach has been taken to circumvent past failures by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol). Our findings showed that administration of amyloid-β 1−42 (Aβ) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before onset of Aβ deposition (7 weeks of age) and/or at an older age (35 weeks of age) is effective in halting the progression and clearing the AD-like neuropathological hallmarks. Passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus) in the brain of treated mice was notably reduced. These results demonstrate that immunization with EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.
Gene amplification in the diagnosis of mycobacterial infections

The number and importance of infections caused by Mycobacterium tuberculosis and other mycobacterial species is increasing. Since the detection and identification of mycobacteria by conventional laboratory methods (cultivation, staining, and biochemical tests) is a slow and complex procedure, rapid diagnostic methods are urgently needed. Several amplification methods based on different techniques have been applied in the detection of mycobacteria directly from clinical specimens. Most experience has been obtained from different polymerase chain reaction (PCR) assays and their general performance is good. However, their sensitivity in the analysis of samples containing small amounts of mycobacteria or samples containing inhibitory substances has been low. Furthermore, the risk of false positives caused by contamination is high, and the clinical relevance of the results may be unclear. Thus, these gene amplification techniques are a valuable adjunct to the diagnosis of mycobacteria, but so far they cannot replace conventional microbiological methods.
Using a ‘domains’ approach to build community empowerment

This paper provides two case study examples of how community empowerment can be better conceptualized, planned and applied within a programme context by using a 'domains' approach. What is new about this approach is that it does not start with a blank slate onto which participants inscribe their own problems or needs but provides a predetermined focus through each of nine 'empowerment domains': Improves participation; Develops local leadership; Increases problem assessment capacities; Enhances the ability to 'ask why'; Builds empowering organizational structures; Improves resource mobilization; Strengthens links to other organizations and people; Creates an equitable relationship with outside agents; and Increases control over programme management. The importance to community development practice is that the approach provides a more systematic means for community empowerment in a programme context.
Recovery in reading: A treatment study of acquired deep dyslexia in Spanish

Background: Adult oral reading in consistent orthographies, like Spanish, is argued to proceed through sublexical spelling-to-sound conversion. Hence, it was surprising that Davies and Cuetos (2005) observed a Spanish-speaking aphasic patient, MJ, who showed some capacity to read words aloud—producing many semantic errors—alongside an inability to read nonwords. MJ's symptoms are congruent with deep dyslexia. We investigated whether her reading could be improved through therapy addressing those deep dyslexic symptoms (de Partz, 1986). Aims: We expected to see joint improvement in word and nonword reading if therapy aimed at facilitating improvement in nonword reading succeeded, due to the consistency of the orthography. We hypothesised that occurrence of semantic paralexias in reading should decrease as reading skills improved. Alternatively, if therapy had led to the establishment of a lexical-semantic reading strategy not available to the patient before injury, then we anticipated the possibility that semantic errors could actually increase in occurrence as more therapy was received over time. Methods & Procedures: Our study began 18 months after MJ's brain injury, and continued over 2 years. Training was given in completing spelling–sound mappings at the level of grapheme–phoneme correspondences, syllables and words, in phoneme awareness and the combination of phonemes, and in word–picture association. We tested oral reading with the same word and nonword stimuli at four time points through the period of our investigation. We analysed accuracy and error types. Outcomes & Results: By the end of our investigation, MJ presented near-normal word reading and greatly improved, though still impaired, nonword reading. Production of semantic errors disappeared. Thus, adding to some previous case studies (Friedman, 1996), our patient's symptoms evolved from those typical of deep dyslexia to those typical of phonological dyslexia. Conclusions: Our findings show that, even in a language with a transparent orthography, readers can be aided by therapy addressing both lexical and non-lexical reading. The implication is that premorbid reading in a transparent orthography may depend on lexical and non-lexical reading. This conclusion is supported by the superior improvement of word compared to nonword reading, and by the decline in production of semantic paralexias accompanying the improvement in reading performance.
CCR5 Plays a Critical Role in Obesity-Induced Adipose Tissue Inflammation and Insulin Resistance by Regulating Both Macrophage Recruitment and M1/M2 Status

C-C motif chemokine receptor (CCR)2 and its ligand, monocyte chemoattractant protein (MCP)-1, are pivotal for adipose tissue macrophage (ATM) recruitment and the development of insulin resistance. However, other chemokine systems also may play a role in these processes. In this study, we investigated the role of CCR5 in obesity-induced adipose tissue inflammation and insulin resistance. We analyzed expression levels of CCR5 and its ligands in white adipose tissue (WAT) of genetically (ob/ob) and high-fat (HF) diet–induced obese (DIO) mice. Furthermore, we examined the metabolic phenotype of Ccr5−/− mice. CCR5 and its ligands were markedly upregulated in WAT of DIO and ob/ob mice. Fluorescence-activated cell sorter analysis also revealed that DIO mice had a robust increase in CCR5+ cells within ATMs compared with chow-fed mice. Furthermore, Ccr5−/− mice were protected from insulin resistance, glucose intolerance, and hepatic steatosis induced by HF feeding. The effects of loss of CCR5 were related to both reduction of total ATM content and an M2-dominant shift in ATM polarization. It is noteworthy that transplantation of Ccr5−/− bone marrow was sufficient to protect against impaired glucose tolerance. CCR5 plays a critical role in ATM recruitment and polarization and subsequent development of insulin resistance.
Alprazolam in young and elderly men: sensitivity and tolerance to psychomotor, sedative and memory effects.

This study was designed to determine whether age influences sensitivity to alprazolam and/or rate of acute tolerance development to the effects of alprazolam. Three treatments were each separated by 4 weeks. Twenty-five young (ages 22-35) and 13 elderly (ages 65-75) men received 2 mg of alprazolam/2 min i.v. Blood samples were obtained over 48 hr, and sedative, psychomotor and memory effects were assessed serially for 12 hr. Clearance was lower (P = .05) and elimination t[1/2] was longer (P = .005) in the elderly, but area under the concentration curve to 12 hr and maximum concentration did not differ by age group. Maximum impairment was greater in the elderly for all assessments. Mean EC50 values differed between the elderly (25.3 and 25.0 ng/ml) and the young (39.8 and 36.5 ng/ml) on card sorting and digit symbol substitution, respectively (P < .001). Bolus treatment data were used to individualize doses for the crossover of placebo and alprazolam; infusions were designed to maintain a plateau alprazolam concentration between 1 and 9 hr. Alprazolam concentrations through 12 hr did not differ between the young and elderly. Median t[1/2] for offset of effect for digit symbol substitution was 2.8 hr in the young and 4.9 hr in the elderly (P = .05). Therefore, aging decreases alprazolam clearance and increases sensitivity to effects of alprazolam through a mechanism other than pharmacokinetics; aging also decreases the rate of offset of effect of alprazolam. In addition, the data provide insight into the intensity of initial effect as a determinant of rate of tolerance development.
Building Trust in the Mission Area: a Weapon Against Terrorism?

Military units on missions abroad face, among other challenges, terrorism. Terrorists are hard to recognize since they operate non-uniformed. Detection of terrorists in the area of operation can best be done by winning the trust of the local population, who can provide information. However, since the military rotates its units regularly, it is hard to build up a trusting relationship with the local population. Other players in the field of international operations are civil aid organisations. They remain in the area for a lengthy period of time, and often build up trusting relationships with the local population. Trust between civil aid organisations and the military is a triple edged sword, as it enables co-operation: the civil aid organisations get the protection they need from the military, the military gets the information it needs through civil aid organisations and the local population is supported in rebuilding society by repressing terrorism.
The price of privacy and the limits of LP decoding

This work is at theintersection of two lines of research. One line, initiated by Dinurand Nissim, investigates the price, in accuracy, of protecting privacy in a statistical database. The second, growing from an extensive literature on compressed sensing (see in particular the work of Donoho and collaborators [4,7,13,11])and explicitly connected to error-correcting codes by Candès and Tao ([4]; see also [5,3]), is in the use of linearprogramming for error correction. Our principal result is the discovery of a sharp threshhold ρ*∠ 0.239, so that if ρ < ρ* and A is a random m x n encoding matrix of independently chosen standardGaussians, where m = O(n), then with overwhelming probability overchoice of A, for all x ∈ Rn, LP decoding corrects ⌊ ρ m⌋ arbitrary errors in the encoding Ax, while decoding can be made to fail if the error rate exceeds ρ*. Our boundresolves an open question of Candès, Rudelson, Tao, and Vershyin [3] and (oddly, but explicably) refutesempirical conclusions of Donoho [11] and Candès et al [3]. By scaling and rounding we can easilytransform these results to obtain polynomial-time decodable random linear codes with polynomial-sized alphabets tolerating any ρ < ρ* ∠ 0.239 fraction of arbitrary errors. In the context of privacy-preserving datamining our results say thatany privacy mechanism, interactive or non-interactive, providingreasonably accurate answers to a 0.761 fraction of randomly generated weighted subset sum queries, and arbitrary answers on the remaining 0.239 fraction, is blatantly non-private.
Language prosody and the right hemisphere

Abstract Groups of right hemisphere damaged, left hemisphere damaged aphasic and normal control subjects were assessed on a series of tests designed to examine discrimination and production of different aspects of linguistic prosody. These included lexical stress, intonation, emphatic stress, lexical stress in sentence contexts, language identification using prosodic cues, and prosody in discourse. The right hemisphere damaged subjects were significantly impaired on all of the tests as compared to the control subjects. Furthermore, they were impaired as compared to the left hemisphere damaged aphasic subjects on some of the tests. The results support the notion that the right hemisphere has an important role in the processing of linguistic prosody.
Pants on Fire? Detecting Children's Lies

While there has been much research on adults' abilities to detect deception, there have been very few studies examining both children's and adults' abilities to detect children's real, spontaneous lies. The present study asked both children and adults to make judgments of children's true and false reports. Participants (N = 156) were shown videotaped sessions of children who were either spontaneously lying or telling the truth. Results indicate that both children's and adults' accuracy for detecting children's true statements was below chance. However, older children were significantly better at detecting lies than both younger children and adults.
A Network-based End-to-End Trainable Task-oriented Dialogue System

Teaching machines to accomplish tasks by conversing naturally with humans is challenging. Currently, developing task-oriented dialogue systems requires creating multiple components and typically this involves either a large amount of handcrafting, or acquiring costly labelled datasets to solve a statistical learning problem for each component. In this work we introduce a neural network-based text-in, text-out end-to-end trainable goal-oriented dialogue system along with a new way of collecting dialogue data based on a novel pipe-lined Wizard-of-Oz framework. This approach allows us to develop dialogue systems easily and without making too many assumptions about the task at hand. The results show that the model can converse with human subjects naturally whilst helping them to accomplish tasks in a restaurant search domain.
Characterization and localization of two ion-binding sites within the pore of cardiac L-type calcium channels

L-type Ca channels from porcine cardiac sarcolemma were incorporated into planar lipid bilayers. We characterized interactions of permeant and blocking ions with the channel's pore by (a) studying the current- voltage relationships for Ca2+ and Na+ when equal concentrations of the ions were present in both internal and external solutions, (b) testing the dose-dependent block of Ba2+ currents through the channels by internally applied cadmium, and (c) examining the dose and voltage dependence of the block of Na+ currents through the channels by internally and externally applied Ca2+. We found that the I-V relationship for Na+ appears symmetrical through the origin when equal concentrations of Na+ are present on both sides of the channel (gamma = 90 pS in 200 mM NaCl). The conductance for outward Ca2+ currents with 100 mM Ca2+ on both sides of the channel is approximately 8 pS, a value identical to that observed for inward currents when 100 mM Ca2+ was present outside only. This provides evidence that ions pass through the channel equally well regardless of the direction of net flux. In addition, we find that internal Cd2+ is as effective as external Cd2+ in blocking Ba2+ currents through the channels, again suggesting identical interactions of ions with each end of the pore. Finally, we find that micromolar Ca2+, either in the internal or in the external solution, blocks Na+ currents through the channels. The affinity for internally applied Ca2+ appears the same as that for externally applied Ca2+. The voltage dependence of the Ca(2+)-block suggests that the sites to which Ca2+ binds are located approximately 15% and approximately 85% of the electric field into the pore. Taken together, these data provide direct experimental evidence for the existence of at least two ion binding sites with high affinity for Ca2+, and support the idea that the sites are symmetrically located within the electric field across L-type Ca channels.
Engineered zinc-finger transcription factors activate OCT4 (POU5F1), SOX2, KLF4, c-MYC (MYC) and miR302/367

Artificial transcription factors are powerful tools for regulating gene expression. Here we report results with engineered zinc-finger transcription factors (ZF-TFs) targeting four protein-coding genes, OCT4, SOX2, KLF4 and c-MYC, and one noncoding ribonucleic acid (RNA) gene, the microRNA (miRNA) miR302/367 cluster. We designed over 300 ZF-TFs whose targets lie within 1 kb of the transcriptional start sites (TSSs), screened them for increased messenger RNA or miRNA levels in transfected cells, and identified potent ZF-TF activators for each gene. Furthermore, we demonstrate that selected ZF-TFs function with alternative activation domains and in multiple cell lines. For OCT4, we expanded the target range to −2.5 kb and +500 bp relative to the TSS and identified additional active ZF-TFs, including three highly active ZF-TFs targeting distal enhancer, proximal enhancer and downstream from the proximal promoter. Chromatin immunoprecipitation (FLAG-ChIP) results indicate that several inactive ZF-TFs targeting within the same regulatory region bind as well as the most active ZF-TFs, suggesting that efficient binding within one of these regulatory regions may be necessary but not sufficient for activation. These results further our understanding of ZF-TF design principles and corroborate the use of ZF-TFs targeting enhancers and downstream from the TSS for transcriptional activation.
Analyzing the Dynamic Evolution of Hashtags on Twitter: a Language-Based Approach

Hashtags are used in Twitter to classify messages, propagate ideas and also to promote specific topics and people. In this paper, we present a linguistic-inspired study of how these tags are created, used and disseminated by the members of information networks. We study the propagation of hashtags in Twitter grounded on models for the analysis of the spread of linguistic innovations in speech communities, that is, in groups of people whose members linguistically influence each other. Differently from traditional linguistic studies, though, we consider the evolution of terms in a live and rapidly evolving stream of content, which can be analyzed in its entirety. In our experimental results, using a large collection crawled from Twitter, we were able to identify some interesting aspects -- similar to those found in studies of (offline) speech -- that led us to believe that hashtags may effectively serve as models for characterizing the propagation of linguistic forms, including: (1) the existence of a "preferential attachment process", that makes the few most common terms ever more popular, and (2) the relationship between the length of a tag and its frequency of use. The understanding of formation patterns of successful hashtags in Twitter can be useful to increase the effectiveness of real-time streaming search algorithms.
Methods for Compensating Contrast Effects in Information Visualization

Color, as one of the most effective visual variables, is used in many techniques to encode and group data points according to different features. Relations between features and groups appear as visual patterns in the visualization. However, optical illusions may bias the perception at the first level of the analysis process. For instance, in pixel‐based visualizations contrast effects make pixels appear brighter if surrounded by a darker area, which distorts the encoded metric quantity of the data points. Even if we are aware of these perceptual issues, our visual cognition system is not able to compensate these effects accurately. To overcome this limitation, we present a color optimization algorithm based on perceptual metrics and color perception models to reduce physiological contrast or color effects. We evaluate our technique with a user study and find that the technique doubles the accuracy of users comparing and estimating color encoded data values. Since the presented technique can be used in any application without adaption to the visualization itself, we are able to demonstrate its effectiveness on data visualizations in different domains.
Sellers’ Revisited: A Big Data Reassessment of Historical Outbreaks of Bluetongue and African Horse Sickness due to the Long-Distance Wind Dispersion of Culicoides Midges

The possibility that outbreaks of bluetongue (BT) and African horse sickness (AHS) might occur via long-distance wind dispersion (LDWD) of their insect vector (Culicoides spp.) was proposed by R. F. Sellers in a series of papers published between 1977 and 1991. These investigated the role of LDWD by means of visual examination of the wind direction of synoptic weather charts. Based on the hypothesis that simple wind direction analysis, which does not allow for wind speed, might have led to spurious conclusions, we reanalyzed six of the outbreak scenarios described in Sellers’ papers. For this reanalysis, we used a custom-built Big Data application (“TAPPAS”) which couples a user-friendly web-interface with an established atmospheric dispersal model (“HYSPLIT”), thus enabling more sophisticated modeling than was possible when Sellers undertook his analyzes. For the two AHS outbreaks, there was strong support from our reanalysis of the role of LDWD for that in Spain (1966), and to a lesser degree, for the outbreak in Cyprus (1960). However, for the BT outbreaks, the reassessments were more complex, and for one of these (western Turkey, 1977) we could discount LDWD as the means of direct introduction of the virus. By contrast, while the outbreak in Cyprus (1977) showed LDWD was a possible means of introduction, there is an apparent inconsistency in that the outbreaks were localized while the dispersion events covered much of the island. For Portugal (1956), LDWD from Morocco on the dates suggested by Sellers is very unlikely to have been the pathway for introduction, and for the detection of serotype 2 in Florida (1982), LDWD from Cuba would require an assumption of a lengthy survival time of the midges in the air column. Except for western Turkey, the BT reanalyses show the limitation of LDWD modeling when used by itself, and indicates the need to integrate susceptible host population distribution (and other covariate) data into the modeling process. A further refinement, which will become increasingly important to assess LDWD, will be the use of virus and vector genome sequence data collected from potential source and the incursion sites.