Miracle-dz/UniFAR-FTUs huggingface dataset:
Pro ﬁ ling the macro ﬁ laricidal effects of ﬂ ubendazole on adult female Brugia malayi using RNAseq

The use of micro ﬁ laricidal drugs for the control of onchocerciasis and lymphatic ﬁ lariasis (LF) necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macro ﬁ laricidal drug. Flubendazole (FLBZ), a benzimidazole anthel-mintic, is an appealing candidate. FLBZ has demonstrated potent macro ﬁ laricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability. A new formulation that enables suf ﬁ cient bioavailability following oral administration could render FLBZ an effective treatment for onchocerciasis and LF. Identi ﬁ cation of drug-derived effects is important in ascertaining a dosage regimen which is predicted to be lethal to the parasite in situ . In previous histological studies, exposure to FLBZ induced damage to tissues required for reproduction and survival at pharmacologically relevant concentrations. However, more precise and quantitative indices of drug effects are needed. This study assessed drug effects using a transcriptomic approach to con ﬁ rm effects observed histologically and to identify genes which were differentially expressed in treated adult female Brugia malayi . Comparative analysis across different concentrations (1 m M and 5 m M) and durations (48 and 120 h) provided an overview of the processes which are affected by FLBZ exposure. Genes with dysregulated expression were consistent with the reproductive effects observed via histology in our previous studies. This study revealed transcriptional changes in genes involved in embryo development. Additionally, signi ﬁ cant downregulation was observed in genes encoding cuticle components, which may re ﬂ ect changes in developing embryos, the adult worm cuticle or both. These data support the hypothesis that FLBZ acts predominantly on rapidly dividing cells, and provides a basis for selecting molecular markers of drug-induced damage which may be of use in predicting ef ﬁ cacious FLBZ regimens. © 2016 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Molecular Mechanisms of Stem Cell Aging

The aging of multicellular organisms is a complex process, which is a result of various mutually complementary causes. One of these causes is the aging of stem cells. The biological function of stem cells is the replacement of cells that are lost due to illness, injury or normal fluctuations in the maintenance of tissue homeostasis. Molecular mechanisms involved in stem cell aging are similar to those involved in the aging of somatic cells. They include DNA damage and mutations, cell senescence, stem cell exhaustion, telomere shortening, epigenetic changes (alterations of histones and DNA and the consequent dysregulation of gene expression), changes in microRNAs, changes in metabolism, nutrient sensing, decline in mitochondrial integrity and biogenesis, alterations in microenvironment, accumulation of paracrine factors, and loss of cell polarity and proteostasis. Stem cells have developed special mechanisms that compensate for age-related accumulations of errors and they manage to maintain their stemness for a long time, however, they are able to keep cells in a good condition only for a limited period. This article describes the various mechanisms of stem cell aging and their consequences. Key words: stem cell; aging; nutrient sensing; niche MOLEKULARNI MEHANIZMI STARANJA MATICNIH CELIC Povzetek: Staranje veccelicnih organizmov je kompleksen proces, ki je posledica razlicnih, med seboj dopolnjujocih se vzrokov. Eden od teh je tudi staranje maticnih celic, katerih bioloska funkcija je nadomescanje celic, ki propadejo zaradi bolezni, poskodb ali normalnega obnavljanja pri ohranjanju homeostaze tkiv. Molekularni mehanizmi, ki so vpleteni v staranje maticnih celic, so podobni kot pri staranju telesnih celic. Vkljucujejo poskodbe DNK in mutacije, celicno senescenco, izcrpavanje zalog maticnih celic, krajsanje telomer, epigenetske spremembe (spremembe histonov in DNKA ter posledicno spremenjeno izražanje genov), spremembe v mikroRNK, spremembe v zaznavanju hranil in presnovi, zmanjsano stevilo mitohondrijev in njihovo oslabljeno funkcijo, spremembe v mikrookolju in kopicenje razlicnih parakrinih dejavnikov ter izgubo celicne polarnosti in proteostaze. Maticne celice so razvile posebne mehanizme, s katerimi kompenzirajo s staranjem povezano kopicenje napak in ohranjajo svojo maticnost, vendar jih ti mehanizmi v dobri kondiciji lahko ohranjajo le dolocen cas. V clanku opisujemo razlicne mehanizme staranja maticnih celic in njihove posledice. Kljucne besede: maticne celice; staranje; hranilna snov; zaznavanje; nisa
Social cancer and the biology of the clonal ant Pristomyrmex punctatus (Hymenoptera: Formicidae)

We review some aspects of the biology of the ant Pristomyrmex punctatus , in which the winged queen caste is absent and wingless females reproduce by thelytokous parthenogenesis. The majority of females have two ovarioles, whereas up to 50% of colonies contain large-bodied females which have four ovarioles. We call the former workers and the latter ergatoid queens. Males are rare. Some ergatoid queens have a spermatheca, but no inseminated individual has been found so far. Castes are morphologically defined, and workers engage in asexual reproduction in all colonies regardless of the presence of ergatoid queens. In colonies containing only workers, reproductive division of labor is regulated by age-polyethism: All young workers reproduce and fulfill inside-nest roles, and old workers become sterile and fulfill outside-nest roles. Colonies are founded by fission or budding, and consequently neighboring colonies are often re-lated. Nevertheless, populations are multi-colonial, with strong hostility among neighboring colonies. A genetic analysis revealed that colonies often have multiple genotypes (parthenogenetic lineages), and suggested that the majority of those lineages can produce both workers and ergatoid queens. However, a lineage in a population in central Japan produces only ergatoid queens. We define these queens as cheaters, as they fulfill no other task than oviposition and therefore depend on the work force of other non-cheater lineages. Ergatoid queens in cheater lineages have three distinct ocelli, but those in non-cheater lineages usually have zero to two. As cheaters are likely to be horizontally transmitted, we draw an analogy to transmissible cancers. The coexistence of cheaters and non-cheaters is discussed in the frameworks of multilevel selection in the short term, and local extinction-immigration in the long term. However, many things remain to be studied, such as the developmental origin of the ergatoid queens
Smart Homes and Quality of Life for the Elderly: Perspective of Competing Models

The percentage of the elderly population has been on rise steadily over the past few years across the globe, which is a cause of serious concern among the research fraternity. A lot of research is going on that tries to harness the benefits of the various information and communication technologies to enable these elderly people to live independently and promote a sense of overall well-being. Although in the evolutionary phase, yet smart homes can help these elderly people in their daily life. However, for the success of such smart systems, the intention of the users towards using those systems must be understood. But, there is a serious lack of relevant exploratory research that tries to measure and explain the adoption of such smart homes by the elderly population from a multiple theory perspective: namely, the technology acceptance model, the theory of reasoned action and the theory of planned behavior. The main aim of this paper is to fill up this void of a lack of theoretical approach by testing the three models in the context of the adoption of smart homes by the elderly population. In order to do so, we conducted a survey with $N = 239$ (after screening) and analyzed the results using the structural equation modeling and confirmatory factor analysis techniques. Results suggest that all the three models are valid although they do not take into account certain factors that are unique to this context. This paper paper provides the initial groundwork to explore the process of adopting smart home services by the elderly with potential future research areas.
Development and Handicap

Preface. 1. The Handicapped Child. 2. How do Blind Children Develop? 3. How do Deaf Children Develop? 4. How do Children with Motor Handicaps Develop? 5. How do Children with Down's Syndrome Develop? 6. How do Autistic Children Develop? 7. Some Practical Implications of the Studies. 8. Some Theoretical Implications of the Studies. References. Index.
Developmental Psychology and You

List of Exercises. List of Figures. List of Tables. Preface and Acknowledgements. 1. What is Developmental Psychology? 2. First Views of the World. 3. First Relationships. 4. Early Influences and Personality. 5. Playing and Learning. 6. Developing Language. 7. Children's Thinking. 8. Intelligence and Experience. 9. Creativity and Artistic Development. 10. Moral and Social Development. 11. Gender Development and Gender Differences. 12. Childhood Problems. 13. Puberty and Adolescence. 14. Growing Older: Young and Middle Adulthood. 15. Growing Old. 16. Studying Development. Glossary. Author Index. Subject Index.
Colour and naming in healthy and aphasic people

Abstract The purpose of this study was to create a paradigm suitable for people with aphasia and healthy subjects to evaluate the influence of colour on naming pictures of objects. We designed a completely new stimulus set based on images of 140 common real objects that were inspired by the Snodgrass and Vanderwart picture set (1980). We were especially interested whether there is a difference in performance between the aphasic patients and the group of healthy controls. Adding chromatic information to pictures of objects shows only a small effect in verification and categorisation tasks. However, when observers are required to name objects, colour speeds performance and enhances accuracy (Rossion & Pourtois, 2004). The present study contrasts two different claims as to why colour may benefit object naming. The first is that colour simply aids the segmentation of the object from its background (Wichmann et al., 2002). The second is that colour may help to elicit a wider range of associations with the object, thereby enhancing lexical access (Bisiach, 1966). To distinguish between these processes an equal number of pictures containing high and low colour diagnostic objects were presented against either fractal noise or uniform backgrounds in a naming task to aphasic subjects with anomia and to healthy controls. Performance for chromatic stimuli was compared with that for monochrome stimuli equated in luminance. Results show that colour facilitates naming significantly in both subject groups and there was no significant difference between objects with high or low colour diagnostic values. We also found that object segmentation and the lexical access seem to occur in parallel processes, rather than in an additive way.
Are actions to verbs as objects are to nouns? On the differential semantic bases of form, class, category

In most extant theories of form-class acquisition, the relationship between the semantic and formal properties of each class is held to be similar. This paper presents arguments that this relationship is in fact different for nouns than for any other lexical class. The semantic notion of concrete object reference functions both as an entree into the category and subsequently as the core which holds this category together, as its subclasses admit of no unified structural description. The basic categorial split in the world's languages is between 'noun' and Other'. Children cannot initially assume that the notions 'action', 'stative property', 'locative relation' will provide entries into the categories verb, adjective, preposition, respectively, first because these categorial distinctions are not universally attested, and second because in those languages that do have them, there is a much looser fit between notion and category. For verbs, for example, small-scale combinatorial properties provide a more reliable characterization than 'action'. It is further argued that a semantic-structural characterization of noun as 'head of argument phrase' provides the child with a less effective entry into the category: not all arguments are noun-headed, and conversely, nouns head constructions which do not function as arguments. In sum, the relationship between the category noun and its semantic characterization is special. The paper concludes with a critique of a previous model of form-class acquisition (Maratsos and Chalkley 1980) in the light of the arguments presented here.
The Neural Correlates of Emotion Regulation by Implementation Intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen! ”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency.
On Convergence of Kronecker Graphical Lasso Algorithms

This paper studies iteration convergence of Kronecker graphical lasso (KGLasso) algorithms for estimating the covariance of an i.i. d. Gaussian random sample under a sparse Kronecker-product covariance model and MSE convergence rates. The KGlasso model, originally called the transposable regularized covariance model by Allen <etal/> [“Transposable regularized covariance models with an application to missing data imputation,” Ann. Appl. Statist. , vol. 4, no. 2, pp. 764–790, 2010], implements a pair of <formula formulatype="inline"><tex Notation="TeX">$\ell_1$</tex> </formula> penalties on each Kronecker factor to enforce sparsity in the covariance estimator. The KGlasso algorithm generalizes Glasso, introduced by Yuan and Lin [“Model selection and estimation in the Gaussian graphical model,” Biometrika, vol. 94, pp. 19–35, 2007] and Banerjee <etal/> [“Model selection through sparse maximum likelihood estimation for multivariate Gaussian or binary data,” J. Mach. Learn. Res., vol. 9, pp. 485–516, Mar. 2008], to estimate covariances having Kronecker product form. It also generalizes the unpenalized ML flip-flop (FF) algorithm of Dutilleul [“The MLE algorithm for the matrix normal distribution,” J. Statist. Comput. Simul. , vol. 64, pp. 105–123, 1999] and Werner <etal/> [“On estimation of covariance matrices with Kronecker product structure,” IEEE Trans. Signal Process. , vol. 56, no. 2, pp. 478–491, Feb. 2008] to estimation of sparse Kronecker factors. We establish that the KGlasso iterates converge pointwise to a local maximum of the penalized likelihood function. We derive high dimensional rates of convergence to the true covariance as both the number of samples and the number of variables go to infinity. Our results establish that KGlasso has significantly faster asymptotic convergence than Glasso and FF. Simulations are presented that validate the results of our analysis. For example, for a sparse 10<formula formulatype="inline"><tex Notation="TeX">$\thinspace$</tex></formula>000<formula formulatype="inline"><tex Notation="TeX">$\,\times\,$</tex></formula>10<formula formulatype="inline"><tex Notation="TeX">$\thinspace$</tex></formula>000 covariance matrix equal to the Kronecker product of two 100<formula formulatype="inline"> <tex Notation="TeX">$\,\times\,$</tex></formula>100 matrices, the root mean squared error of the inverse covariance estimate using FF is 2 times larger than that obtainable using KGlasso for sample size of <formula formulatype="inline"> <tex Notation="TeX">$n=100$</tex></formula>.
Propofol infusion in children – a reply

2014; 42: 1592–600. 3. Kam PC, Cardone D. Propofol infusion syndrome. Anaesthesia 2007; 62: 690–701. 4. Fraser GL, Devlin JW, Worby CP, et al. Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials. Critical Care Medicine 2013; 41: S30–8. 5. Barnes SS, Kudchadkar SR. Sedative choice and ventilator-associated patient outcomes: don’t sleep on delirium. Annals of Translational Medicine 2016; 4: 34. 6. Mirrakhimov AE, Voore P, Halytskyy O, Khan M, Ali AM. Propofol infusion syndrome in adults: a clinical update. Critical Care Research and Practice 2015; 2015: 260385.
Dopamine D4 receptor activation restores CA1 LTP in hippocampal slices from aged mice

Normal aging is characterized with a decline in hippocampal memory functions that is associated with changes in long‐term potentiation (LTP) of the CA3‐to‐CA1 synapse. Age‐related deficit of the dopaminergic system may contribute to impairment of CA1 LTP. Here we assessed how the modulation of CA1 LTP by dopamine is affected by aging and how it is dependent on the Ca2+ source. In slices from adult mice, the initial slope of the field potential showed strong LTP, but in slices from aged mice LTP was impaired. Dopamine did not affect LTP in adult slices, but enhanced LTP in aged slices. The dopamine D1/D5 receptor (D1R/D5R) agonist SKF‐81297 did not affect LTP in adult but caused a relative small increase in LTP in aged slices; however, although there was no difference in dopamine D4 receptor (D4R) expression, the D4R agonist PD168077 increased LTP in aged slices to a magnitude similar to that in adult slices. The N‐Methyl‐D‐aspartate receptor antagonist D‐AP5 reduced LTP in adult slices, but not in aged slices. However, in the presence of D‐AP5, PD168077 completely blocked LTP in aged slices. The voltage‐dependent calcium channel (VDCC) blocker nifedipine reduced LTP in adult slices, but surprisingly enhanced LTP in aged slices. Furthermore, in the presence of nifedipine, PD168077 caused a strong enhancement of LTP in aged slices to a magnitude exceeding LTP in adult slices. Our results indicate that the full rescue of impaired LTP in aging by the selective D4R activation and that a large potentiation role on LTP by co‐application of D4R agonist and VDCC blocker may provide novel strategies for the intervention of cognitive decline of aging and age‐related diseases.
Reference drug pricing.

In his commentary, Aslam Anis correctly points out that there is a greater need for randomized trials to assess the therapeutic equivalence of prescription drugs within a class. [1][1] However, he misinterpreted our results[2][2] when he stated that the reference drug pricing policy led to a “10%
A Prefetching Scheme Exploiting both Data Layout and Access History on Disk

Prefetching is an important technique for improving effective hard disk performance. A prefetcher seeks to accurately predict which data will be requested and load it ahead of the arrival of the corresponding requests. Current disk prefetch policies in major operating systems track access patterns at the level of file abstraction. While this is useful for exploiting application-level access patterns, for two reasons file-level prefetching cannot realize the full performance improvements achievable by prefetching. First, certain prefetch opportunities can only be detected by knowing the data layout on disk, such as the contiguous layout of file metadata or data from multiple files. Second, nonsequential access of disk data (requiring disk head movement) is much slower than sequential access, and the performance penalty for mis-prefetching a randomly located block, relative to that of a sequential block, is correspondingly greater. To overcome the inherent limitations of prefetching at logical file level, we propose to perform prefetching directly at the level of disk layout, and in a portable way. Our technique, called DiskSeen, is intended to be supplementary to, and to work synergistically with, any present file-level prefetch policies. DiskSeen tracks the locations and access times of disk blocks and, based on analysis of their temporal and spatial relationships, seeks to improve the sequentiality of disk accesses and overall prefetching performance. It also implements a mechanism to minimize mis-prefetching, on a per-application basis, to mitigate the corresponding performance penalty. Our implementation of the DiskSeen scheme in the Linux 2.6 kernel shows that it can significantly improve the effectiveness of prefetching, reducing execution times by 20%--60% for microbenchmarks and real applications such as grep, CVS, and TPC-H. Even for workloads specifically designed to expose its weaknesses, DiskSeen incurs only minor performance loss.
Contemporary Voting Rights Controversies Through the Lens of Disability

People with disabilities are the ticking time bomb of the electorate. An estimated thirty to thirty-five percent of all voters in the next twenty-five years will need some form of accommodation. Despite the significant and growing population of voters with disabilities, they do not vote in proportion to their numbers. We can consider voters with disabilities as “the canaries in the coal mine,” the people who are an advanced warning of the structural difficulties in voting not just for themselves, but also for the system as a whole. Solving problems in voting for people with disabilities will strengthen the entire system and will help improve the voting process for everyone, especially people from disempowered communities. Furthermore, although election law scholars have largely ignored the unique voting problems confronting voters with disabilities, virtually every major voting controversy in contemporary American electoral politics directly implicates issues of disability.This Article examines the state of disability access to voting in the lead-up to the 2016 election, revealing an electoral problem that has been lurking in the background for far too long. Current debates about access to voting and voter restrictions often ignore the current legal landscape’s disparate effect on those with disabilities. The insights in this Article offer another angle of intervention towards ameliorating the problems in the voting process for disempowered individuals. This call for reform is timely in light of the upcoming presidential election. We tend to think of problems of voting and disability, if we think of them at all, as classic issues of physical access. But in fact, the contemporary problems with respect to voting that preoccupy election lawyers are also heavily implicated by disability as well and moreover are central to the inquiry. This Article reveals those hidden disability implications of our contemporary election law problems.