Miracle-dz/UniFAR-FTUs huggingface dataset:
A deletion mutation in the SH2-N domain of Shp-2 severely suppresses hematopoietic cell development

Shp-1 and Shp-2 are cytoplasmic protein tyrosine phosphatases that contain two Src homology 2 (SH2) domains. A negative regulatory role of Shp-1 in hematopoiesis has been strongly implicated by the phenotype of motheaten mice with a mutation in the Shp-1 locus, which is characterized by leukocyte hypersensitivity, deregulated mast cell function, and excessive erythropoiesis. A targeted deletion of 65 amino acids in the N-terminal SH2 (SH2-N) domain of Shp-2 leads to an embryonic lethality at midgestation in homozygous mutant mice. To further dissect the Shp-2 function in hematopoietic development, we have isolated homozygous Shp-2 mutant embryonic stem (ES) cells. Significantly reduced hematopoietic activity was observed when the mutant ES cells were allowed to differentiate into embryoid bodies (EBs), compared to the wild-type and heterozygous ES cells. Further analysis of ES cell differentiation in vitro showed that mutation in the Shp-2 locus severely suppressed the development of primitive and definitive erythroid progenitors and completely blocked the production of progenitor cells for granulocytes-macrophages and mast cells. Reverse transcriptase PCR analysis of the mutant EBs revealed reduced expression of several specific marker genes that are induced during blood cell differentiation. Stem cell factor induction of mitogen-activated protein kinase activity was also blocked in Shp-2 mutant cells. Taken together, these results indicate that Shp-2 is an essential component and primarily plays a positive role in signaling pathways that mediate hematopoiesis in mammals. Furthermore, stimulation of its catalytic activity is not sufficient, while interaction via the SH2 domains with the targets or regulators is necessary for its biological functions in cells. The in vitro ES cell differentiation assay can be used as a biological tool in dissecting cytoplasmic signaling pathways.
Distribution of Dexamethasone and Preservation of Inner Ear Function following Intratympanic Delivery of a Gel-Based Formulation

Intratympanic (IT) delivery of drugs to the ear is increasingly used for both clinical and research purposes. One limitation of IT delivery is that drugs are rapidly lost from the middle ear by a number of processes, so that prolonged delivery of drug is technically difficult. In the present study, the delivery characteristics of a poloxamer hydrogel formulation containing dexamethasone (dex) were evaluated. The gel is liquid at room temperature, allowing IT injection, but transitions to a gel at body temperature, providing a prolonged residence time in the middle ear. A 50-µl volume of control or dex-containing gel (dex-gel) was injected through the tympanic membrane of guinea pigs. Cochlear function was assessed with cochlear action potential and acoustic emission thresholds measured immediately, 6 or 24 h after IT gel injection. After 6- or 24-hour treatment with dex-gel, perilymph drug gradients along the cochlea were assessed by taking samples sequentially from the apex, and endolymph was sampled from the basal turn. Control gel injections caused small changes in sound field calibrations and functional measures for low-frequency stimuli, consistent with an induced conductive loss. Within 24 h, responses returned to normal. Twenty-four hours after dex-gel injection, low-frequency changes remained as the dex-gel was retained better in the middle ear, but there was no indication of high-frequency loss. While perilymph sample data showed that dex gradients were substantially lower than after single injections of dex solution, quantitative analysis of this result suggests that some dex may have entered the perilymph through the thin bone in the apical region of the cochlea. Endolymph levels of dex remained lower than those in the perilymph. This study confirms that a poloxamer hydrogel-based dex formulation provides an effective method for a prolonged delivery, providing a more uniform distribution of drug in the inner ear.
Regulation of oligodendrocyte differentiation: Protein kinase C activation prevents differentiation of O2A progenitor cells toward oligodendrocytes

Oligodendrocytes differentiate on a specific schedule in vivo in order to myelinate axons at the precise time and at the appropriate position. The current study was undertaken to obtain further insight as to how this timed appearance is regulated intracellularly. We observed that exposure of O2A progenitor cells in culture to phorbol 12‐myristate 13‐acetate (PMA; an activator of protein kinase C, PKC) inhibited their differentiation to oligodendrocytes by suppressing the expression of specific myelin markers at the O4‐stage. To positively identify a role of PKC per se in differentiation, the use of a minimal medium with low serum content turned out to be essential. This was demonstrated by showing that the inhibitory effect of PMA on oligodendrocyte differentiation could be completely abolished by a combined action of insulin, triiodothyronine (T3), hydrocortisone and other components of a chemically defined medium (CDM). Furthermore, the PMA‐mediated inhibition of oligodendrocyte differentiation could be partially restored by activation of the cAMP signal transduction pathway. The results indicate that PKC plays a crucial role in the differentiation of O2A progenitor cells toward oligodendrocytes: PKC activation prevents differentiation of O2A progenitor cells, whereas differentiation toward oligodendrocytes is dependent on other signaling compounds which may counteract the PKC signal transduction route. GLIA 22:121–129, 1998. © 1998 Wiley‐Liss, Inc.
Efficiency of weight gain of serial slaughtered bulls of a five-breed diallel.

Weight and feed consumption of 197 bulls were recorded monthly in a serial slaughter experiment continuing over a period of 24 mo. The bulls were produced in a modified five-breed diallel of the Angus, Brahman, Hereford, Holstein and Jersey breeds. Our objective was to estimate efficiency of feed conversion for weight gain for each breed and cross. The model included average weight gain per day (ADG) as a dependent variable; independent variables included breed-type, season, month within season, average feed intake per day (ADI), initial weight, weight to the . 75 power, breed x ADI and season x ADI effects. The sum of the partial regression coefficients of ADG on ADI and on breed x ADI adjusted for season, month within season, initial weight, weight to the . 75 power and season x ADI was interpreted to be an estimate of intrinsic or net efficiency of ADG. There were no significant differences among the various breed-types in intrinsic efficiency of ADG. Average heterosis for intrinsic efficiency of feed conversion was not significant. None of the contrasts among breed-types was significant for intrinsic efficiency of ADG (British vs dairy, 1.1 +/- 12.3 g/d; Brahman-dairy crosses vs British-dairy crosses, 32.7 +/- 12.9 g/d; British-Brahman crosses vs British-dairy crosses, 13.9 +/- 12.4 g/d; British-Brahman crosses vs straightbred British 3.2 +/- 14.8 g/d).
An examination of recall measures of sponsorship awareness

In four experiments we consider various memory recall techniques in measuring sponsorship awareness effects. Specifically, we investigate event cued recall, brand category cued recall, brand cued recall, and free recall. We also consider the impact of competitor brand presence at the time of sponsorship exposure on sponsorship awareness. Results show that recall measures can differ depending on the cue utilized, and that non-sponsor competitor brands can elicit event recall even when not previously mentioned in association with the event. Further, while competitor presence was detrimental to cued recall, it appeared to facilitate free recall.
Outcome after heart transplantation from older donor age: expanding the donor pool.

OBJECTIVES There has been a progressive expansion of heart donor selection criteria, including higher age limit. We analysed the impact of using hearts from older age donors (>50 years). METHODS Between November 2003 and December 2012, 228 heart transplantations were performed. Children and patients requiring ventricular assistance prior to transplantation were excluded. Recipients from 26 donors aged ≥ 50 years (Group A) were compared with those of 136 donors <40 years (Group B). Patient and donor criteria were identical in both groups. RESULTS Group A recipients were older than those in Group B (59 ± 11 vs 53 ± 11; P < 0.01), and tended to have more ischaemic cardiomyopathy (50 vs 35%; P = 0.16), be in intensive care (31 vs 27%; P = 0.65) and have longer waiting time (56 ± 49 vs 41 ± 47 days; P = 0.15). There were also significant differences in ischaemic time (65 ± 27 vs 93 ± 35 min; P < 0.01). Thirty-day mortality was similar (3.8 vs 3.7%; P = 0.97). Follow-up was 55 ± 32 months. Actuarial survival at 1, 3 and 5 years was 84 ± 7% for Group A and 90 ± 3, 86 ± 3 and 81 ± 4%, respectively, for Group B (P = 0.85). There were no survival differences between patients younger and older than 60 years, but there was a tendency for decreased survival free from cardiac allograft vasculopathy (CAV) in Group A compared to Group B (at 8 years 65 ± 18 vs 78 ± 7%; P = 0.06). CONCLUSIONS Parameters of exclusion of donor hearts can and must be adjusted, since the use of selected marginal donors associated with short ischaemic times appears to have no negative impact on morbidity and mortality, more importantly when compared with mortality on the waiting list.
Characterizing Twitter with Respondent-Driven Sampling

Twitter as one of the most important microblogging online social networks has attracted more than 200 million users in recent years. Although there have been several attempts on characterizing the Twitter by using incomplete sampled data, they have not been very successful to estimate the characteristics of the whole network. In this paper, we characterize Twitter by sampling from its social graph and user behaviors through a random walk based sampling technique called Respondent-Driven Sampling (RDS). To the best of our knowledge, for the first time RDS method and its estimator are used in order to obtain uniform unbiased estimation of several key structural and behavioral properties of Twitter. We compared the performance of the proposed method with other sampling methods such as Metropolis-Hasting Random Walk (MHRW) and sampling from active users (Timeline) against the uniform sampling (UNI). In order to gather the required data, we have implemented four independent crawlers. Our experimental results indicate that the RDS method exhibits lower estimation errors to the sample in- and out-degree distribution compared to MHRW and Timeline. We also show that RDS is more suitable to sample the followers vs. followings ratio, and the correlation between followers/followings vs. tweets.
Managing semantic annotations on medicinal plants

Images repositories would become a costly and meaningless data pool without descriptive metadata. The ability to represent pharmacobotanical semantics is of great importance when teaching and registering biological data about medicinal plants. It will not only enhance discovery and retrieval of knowledge, but it will also enable its translation and reuse in contexts other than the original one. This paper addresses the issues of capturing knowledge necessary to register and retrieve pharmacobatonical data using semantic descriptions. We depict an architecture for automating the semantic annotation of botanical materials based on ontological concepts. The approach is illustrated a case study on annotating data sources containing representations of Brazilian medicinal plants.
Discussion on “Surrogate Measures and Consistent Surrogates”

Surrogates which allow one to predict the effect of the treatment on the outcome of interest from the effect of the treatment on the surrogate are of importance when it is difficult or expensive to measure the primary outcome. Unfortunately, the use of such surrogates can give rise to paradoxical situations in which the effect of the treatment on the surrogate is positive, the surrogate and outcome are strongly positively correlated, but the effect of the treatment on the outcome is negative, a phenomenon sometimes referred to as the “surrogate paradox. ” New results are given for consistent surrogates that extend the existing literature on sufficient conditions that ensure the surrogate paradox is not manifest. Specifically, it is shown that for the surrogate paradox to be manifest it must be the case that either there is (i) a direct effect of treatment on the outcome not through the surrogate and in the opposite direction as that through the surrogate or (ii) confounding for the effect of the surrogate on the outcome, or (iii) a lack of transitivity so that treatment does not positively affect the surrogate for all the same individuals for whom the surrogate positively affects the outcome. The conditions for consistent surrogates and the results of the article are important because they allow investigators to predict the direction of the effect of the treatment on the outcome simply from the direction of the effect of the treatment on the surrogate. These results on consistent surrogates are then related to the four approaches to surrogate outcomes described by Joffe and Greene (2009, Biometrics 65, 530–538) to assess whether the standard criteria used by these approaches to assess whether a surrogate is “good” suffice to avoid the surrogate paradox.
ATM communications network control by neural networks

A learning method that uses neural networks for service quality control in the asynchronous transfer mode (ATM) communications network is described. Because the precise characteristics of the source traffic are not known and the service quality requirements change over time, building an efficient network controller which can control the network traffic is a difficult task. The proposed ATM network controller uses backpropagation neural networks for learning the relations between the offered traffic and service quality. The neural network is adaptive and easy to implement. A training data selection method called the leaky pattern table method is proposed to learn precise relations. The performance of the proposed controller is evaluated by simulation of basic call admission models.
A Survey on Scheduling and the Attributes of Task Scheduling in the Cloud

3 Abstract: Cloud Computing is the latest new trend that is growing rapidly in this era of technological advancements. The word "Cloud'' is a conglomeration of computers and servers accessed via the Internet and this makes everyone in this world to access their documents and applications from anywhere and at any time. Scheduling is blooming as a vital research area in the field of Cloud Computing . It aims to map the appropriate tasks, jobs to the resources that are available by keeping in mind the QoS (Quality of Service) requirements of the user. The on-demand service in the Cloud is one of the guiding factor to discover new scheduling strategies. This paper surveys on Scheduling, the types of job scheduling algorithms, types of task Scheduling, and the attributes of Task scheduling.
Effects of haptic feedback on gaze based auto scrolling

Eye tracking enables automatic scrolling based on natural viewing behavior. We were interested in the effects of haptic feedback on gaze behavior and user experience. We conducted an experiment where haptic feedback was used to forewarn the reader that their gaze had entered an active scrolling area. Results show no statistical differences between conditions with or without haptic feedback on task time or gaze behavior. However, user experience varied a lot. Some participants were not able to associate the haptics and the scrolling. Those who understood the connection found the haptic feedback useful. Further research is required to find out a delay between the forewarning and the start of scrolling that is short enough to make the association but yet long enough to support the feeling of control and enjoyable user experience.
Liderazgo auténtico. Concepto y validación del cuestionario ALQ en España

Authentic leadership. Concept and validation of the ALQ in Spain. This study presents the validation of the Authentic Leadership Questionnaire (ALQ) in a sample of more than 600 Spanish employees. This questionnaire measures four distinct but related substantive components of authentic leadership. These components are: self-awareness, relational transparency, balanced processing, and internalized moral perspective. Structural equation modeling confirmed that the Spanish version of ALQ has high reliability and predictive validity for important leadership outputs such as perceived effectiveness of leadership, followers' extra effort and satisfaction with the leader.
Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery

The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300∼700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.
Subthalamic nucleus stimulation reduces abnormal motor cortical overactivity in Parkinson disease.

BACKGROUND Based on the basal ganglia model, it has been hypothesized that the efficacy of high-frequency stimulation of the subthalamic nucleus (STN) against parkinsonian symptoms relies on the activation of cortical premotor regions. In previous positron emission tomography activation studies, STN high-frequency stimulation was associated with selective activation of midline premotor areas during hand movements but mainly reduced the regional cerebral blood flow in movement-related areas, peculiarly at rest. OBJECTIVE To investigate with positron emission tomography the role of regional cerebral blood flow reduction in the clinical improvement provided by STN high-frequency stimulation. METHODS Seven patients with advanced Parkinson disease, who were markedly improved by bilateral STN high-frequency stimulation, underwent positron emission tomography with H2(15)O while the right STN electrode was turned off. The patients were studied at rest and during right-hand movements in 3 electrode conditions: no stimulation, inefficient low-frequency stimulation, and efficient high-frequency stimulation. RESULTS The main effect of high-frequency stimulation was to reduce regional cerebral blood flow in the left primary sensorimotor cortex, the lateral premotor cortex, the right cerebellum, and the midline premotor areas. The selective activation of the anterior cingulate cortex and the left primary sensorimotor cortex during hand movement under STN high-frequency stimulation was attributed to decreased regional cerebral blood flow at rest, rather than increased activation induced by STN high-frequency stimulation. Akinesia was correlated with the abnormal overactivity in the contralateral primary sensorimotor cortex and the ipsilateral cerebellum. CONCLUSION High-frequency stimulation of the STN acts through the reduction of abnormal resting overactivity in the motor system, allowing selective cortical activation during movement.
Relationship between adherence, symptoms, treatment attitudes, satisfaction, and side effects in prisoners taking antipsychotic medication

Objective: To examine the nature and clinical correlates of adherence in prisoners prescribed antipsychotic medication, and how these differ from findings in people taking antipsychotic medication who are not in prison. Method: Treatment adherence, satisfaction with antipsychotic medication, drug attitudes, symptoms, medication side effects, and insight (and insight dimensions) were assessed in 44 prisoners taking antipsychotic medication. Results: In a regression model, 52% of prisoners' adherence to antipsychotic medication was predicted by three explanatory variables: ‘I feel motivated to take my antipsychotic medication’; ‘My antipsychotic medication makes me feel better’; and putting on weight. Conclusion: Adherence interventions for prisoners taking antipsychotic medication may benefit from focusing on increasing personal relevance/benefit from medication and on enhancing motivation to stick with treatment.
On instantaneous amplitude and phase of signals

In many questions of signal processing, it is important to use the concepts of instantaneous amplitude or phase of signals. This is especially the case in communication systems with amplitude or frequency modulation. These concepts are often introduced empirically. However, it is well known that the correct approach for this purpose is to use the concept of analytic signal. Starting from this point, we show some examples of contradictions appearing when using other definitions of instantaneous amplitude or frequency that are commonly admitted. This introduces the problem of characterizing pure amplitude-modulated or pure phase-modulated signals. It is especially shown that whereas amplitude modulated signals can be characterized by spectral considerations, this is no longer the case for phase-modulated signals. Furthermore, signals with constant amplitude have very specific properties, which are analyzed in detail. Some consequences and extensions to random signals are finally discussed.
Internalization and intracellular sorting of the EGF receptor: a model for understanding the mechanisms of receptor trafficking

The epidermal growth factor receptor (EGFR; also known as ErbB1) is one of four related receptor tyrosine kinases. These receptors (EGFR, ErbB2, ErbB3 and ErbB4) are frequently overexpressed in cancer and such overexpression is associated with poor clinical outcome. Understanding the mechanisms involved in growth-factor-receptor downregulation is medically important, as several drugs that interfere with the function and trafficking of ErbB proteins are currently being developed or are already in clinical trials. EGFR has become a model protein for understanding the biology and endocytosis of related growth-factor receptors, and the mechanisms involved in its endocytosis and degradation have been scrutinized for several decades. Nevertheless, the details and principles of these processes are still poorly understood and often controversial. In particular, the literature describing how the ubiquitylation and recruitment of EGFR to clathrin-coated pits are connected is inconsistent and confusing. In this Opinion article, we discuss the impact of signaling motifs, kinase activity and ubiquitylation on clathrin-dependent endocytosis and lysosomal sorting of EGFR. In addition, we discuss potential explanations for contradicting reports, and propose models for the recruitment of ligand-activated EGFR to clathrin-coated pits as well as for lysosomal sorting of ligand-activated EGFR.