Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathogenesis and management of acute myeloid leukemia that has evolved from a myeloproliferative neoplasm

Purpose of reviewThe myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera and primary myelofibrosis (PMF), are a heterogeneous group of myeloid-derived chronic haematopoietic malignancies. Frequent clinical consequences of these diseases include not only an increased risk of thrombosis but also leukemic transformation, which carries a particularly poor prognosis. Here, we discuss the recent identification of risk factors for leukemic transformation, elucidate mechanisms contributing to leukemic transformation, as well as highlight the development of new treatment strategies. Recent findingsSignificant progress in the understanding of the biology of MPNs has been made in recent years, particularly with the discovery that mutations in the JAK-STAT signaling pathway cause unregulated activation. These genetic insights have been extended to leukemic transformation and have revealed a host of genetic alterations that occur at the time of transformation, and that may identify patients at risk for leukemic transformation. Such studies have demonstrated that acute myeloid leukemia (AML) evolved from a chronic phase MPN is distinct from de-novo AML both genetically and clinically given its resistance to conventional antileukemic therapy. SummaryLeukemic transformation of an MPN remains a significant clinical challenge. Recent advances in the understanding of the molecular events that contribute to the development of leukemic transformation will need to be utilized in order to produce rational therapeutic approaches for this largely fatal disease.
Advertising Effectiveness, Brand Switching and Market Dynamics

ADVERTISING can be used to create an experimental market environment. It can keep consumer brand purchase decisions fluid. In a sense it is and can be used to influence potential customers to keep an open mind and to seek out as time goes by the ever improved products and brands. Brand preferences play an extremely significant role in the dynamical aspects of marketing activity. Business men who have sought to use the power of advertising to create new markets and to sustain old ones have always required better ways to measure the effectiveness of advertising and promotional activity. In the following article a new method for studying advertising effects will be presented. It differs from other methods in that it takes into account measures of the strengths of competitors. The basic indicator of competitive strength and weakness is a brand switching, loyalty index. A person may have strong or weak brand preferences. He may always buy a given brand of razor blades, of soap, of margarine, of automobile, of coffee or he may switch from one brand to another either in some describable patterned way or in some haphazard way. Groups of persons can be similarly regarded. For example, at a given time it may be presumed that the current users of a given brand have in their minds to stay loyal or to switch to some other brand the next time that they intend to buy. By combining quantitative facts about brand preference with some fairly simple probability mathematics it is possible to develop ways to study Market Dynamics. Brand preferences can be directly influenced by advertising activity in the short run. Sales can be 'pulsed'; special promotions do have an effect. Linking together brand preferences and advertising activity with proper field experimentation it is possible to get estimates of advertising effectiveness. In the following article two major discussions will be developed, in a narrative form. The method employed will be that of numerical illustration for reasons of ease of understanding.2 The first illustration will refer to a set of experimental situations in which the problem is
The sharpening of frequency tuning curves requires patterned activity during development in the mouse, Mus musculus

Neural activity has been implicated as having both a trophic function and a role in synaptic specificity. Sensory deprivation studies in a large number of developing systems have resulted in the pathological morphology of neurons and abnormal response properties. If the relative timing of discharge among afferent terminals is a cue employed by the developing system to refine the array of synaptic connections, then altering the discharge patterns should hinder this process. In the present experiments, we investigate the role played by the temporal pattern of neural activity during the ontogeny of frequency tuning in the mouse central auditory system. Postnatal animals were exposed to acoustic stimuli, repetitive clicks, that continuously entrained a large proportion of primary afferents from the onset of hearing until an age at which tuning curves should have been adult-like. The amount of fatigue to repetitive clicks was characterized at the level of the eighth nerve and inferior colliculus in normal animals. Frequency tuning curves obtained from the inferior colliculus were used as an assay for the specificity of neural connections. Click-reared animals had significantly broader tuning curves than did normally reared mice, particularly for units with best frequencies in the 10- to 15-kHz range. Furthermore, it was found that this change could not be attributed to the selective loss of the sustained component of the response. The affected range is interpreted in terms of the frequency spectrum of the click and the fact that lower frequency regions of the inferior colliculus were found to habituate rapidly. The click-rearing environment did not appear to affect unit spontaneous activity or response latency, nor did it alter the tonotopic map in the inferior colliculus. We argue against the possibility of cochlear damage based on threshold and high frequency cutoff measurements. Mice were reared in a second acoustic environment, repetitive pulses of two added frequencies, as a control for the effects of the click stimulus. This rearing paradigm did not lead to a broadening of tuning curves. It did, however, alter the properties of bimodal tuning curves. For units with bimodal tuning curves having best frequencies in the range of the rearing frequencies, it was found that the second excitatory area had a lower than normal threshold. In addition, the frequency range separating the peaks of the two excitatory regions was statistically smaller. These results are discussed with reference to the specific frequencies used in the rearing paradigm.
Interactive presentation abstract: Reusing of properties after discretization of hybrid automata

When designing embedded systems, often the need arises to model systems having a mixed discrete and continuous behavior (i.e., hybrid systems) that cannot be characterized faithfully using either only discrete or only continuous MoCs (models of computation). Hybrid automata [1] have been proved to be a powerful MoC for the design and verification of hybrid systems, but their high-level of abstraction cannot take into account all the details of the typical HW/SW designs. For this reason, once the hybrid model of the system is proved to be correct, is still necessary to derive an implementable model of the hybrid system. Very few works in literature have focused on developing techniques for extracting a correct by construction HW/SW implementation from hybrid automata [2], [3]. Unfortunately, these approaches are able to refine, into a systematic way, only a subclass of hybrid automata, thus they allow to automatically implement only a small class of hybrid systems. For this reason, it is not uncommon to manually refine hybrid automata into their corresponding discrete (e.g., SystemC [4]) or (approximated) continuous implementations (e.g., SystemC-AMS [4], Matlab Simulink). In such a case the refined system must be verified again to guarantee its correctness. In this context, it would be valuable to reuse as much as possible properties defined for the verification of hybrid automata to reduce the need of an error prone and time consuming ex-novo property definitions. To the best of our knowledge the refinement of formal properties from the hybrid into the discrete domains is still an open problem. The proposed methodology aims to fill this gap.
Influence of interhemispheric interactions on motor function in chronic stroke

In patients with chronic stroke, the primary motor cortex of the intact hemisphere (M1intact hemisphere) may influence functional recovery, possibly through transcallosal effects exerted over M1 in the lesioned hemisphere (M1lesioned hemisphere). Here, we studied interhemispheric inhibition (IHI) between M1intact hemisphere and M1lesioned hemisphere in the process of generation of a voluntary movement by the paretic hand in patients with chronic subcortical stroke and in healthy volunteers. IHI was evaluated in both hands preceding the onset of unilateral voluntary index finger movements (paretic hand in patients, right hand in controls) in a simple reaction time paradigm. IHI at rest and shortly after the Go signal were comparable in patients and controls. Closer to movement onset, IHI targeting the moving index finger turned into facilitation in controls but remained deep in patients, a finding that correlated with poor motor performance. These results document an abnormally high interhemispheric inhibitory drive from M1intact hemisphere to M1lesioned hemisphere in the process of generation of a voluntary movement by the paretic hand. It is conceivable that this abnormality could adversely influence motor recovery in some patients with subcortical stroke, an interpretation consistent with models of interhemispheric competition in motor and sensory systems.
Dopamine D1 receptor-stimulated release of acetylcholine in rat striatum is mediated indirectly by activation of striatal neurokinin1 receptors.

Activation of dopamine D1 receptors is thought to stimulate release of striatal acetylcholine (ACh) indirectly, possibly through local release of substance P which, in turn, may enhance release of ACh. To test this hypothesis, in vivo microdialysis was used to assess the effect of neurokinin1 (NK1) receptor blockade on D1 agonist-induced increases in ACh release in the striatum of awake, freely moving rats with and without a unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal pathway. Local perfusion with the D1 agonist (+-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3- benzazepine-7,8-diol hydrochloride (SKF 38393; 1-25 microM for 20 min) increased striatal ACh release in both intact rats and rats with a 6-hydroxydopamine-induced lesion, although the increase was greater in magnitude in rats with a lesion. Local application of the NK1 antagonist, (2S,3S)-cis-2-(diphenylmethyl)-N- [(methoxyphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine (CP-96,345; 10 and 25 microM), but not its less active enantiomer (2R,3R)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1- azabicyclo[2.2.2]octan-3-amine (CP-96,344; 10 and 25 microM), decreased the elevation in ACh induced by SKF 38393 in both intact rats and rats treated with 6-hydroxydopamine. Systemic administration of the NK1 antagonist 17-beta-hydroxy-17-a-androstanol[3.2- b]pyrimidol[1,2-a]benzimidazole hydrochloride (WIN 51,708; 20 mg/kg i.p.) also reduced the increase in ACh release induced by local perfusion of SKF 38393. (ABSTRACT TRUNCATED AT 250 WORDS)
Testing the equivalence of modern human cranial covariance structure: Implications for bioarchaeological applications.

OBJECTIVES Estimation of the variance-covariance (V/CV) structure of fragmentary bioarchaeological populations requires the use of proxy extant V/CV parameters. However, it is currently unclear whether extant human populations exhibit equivalent V/CV structures. MATERIALS AND METHODS Random skewers (RS) and hierarchical analyses of common principal components (CPC) were applied to a modern human cranial dataset. Cranial V/CV similarity was assessed globally for samples of individual populations (jackknifed method) and for pairwise population sample contrasts. The results were examined in light of potential explanatory factors for covariance difference, such as geographic region, among-group distance, and sample size. RESULTS RS analyses showed that population samples exhibited highly correlated multivariate responses to selection, and that differences in RS results were primarily a consequence of differences in sample size. The CPC method yielded mixed results, depending upon the statistical criterion used to evaluate the hierarchy. The hypothesis-testing (step-up) approach was deemed problematic due to sensitivity to low statistical power and elevated Type I errors. In contrast, the model-fitting (lowest AIC) approach suggested that V/CV matrices were proportional and/or shared a large number of CPCs. Pairwise population sample CPC results were correlated with cranial distance, suggesting that population history explains some of the variability in V/CV structure among groups. DISCUSSION The results indicate that patterns of covariance in human craniometric samples are broadly similar but not identical. These findings have important implications for choosing extant covariance matrices to use as proxy V/CV parameters in evolutionary analyses of past populations.
Ribose catabolism of Escherichia coli: characterization of the rpiB gene encoding ribose phosphate isomerase B and of the rpiR gene, which is involved in regulation of rpiB expression

Escherichia coli strains defective in the rpiA gene, encoding ribose phosphate isomerase A, are ribose auxotrophs, despite the presence of the wild-type rpiB gene, which encodes ribose phosphate isomerase B. Ribose prototrophs of an rpiA genetic background were isolated by two different approaches. Firstly, spontaneous ribose-independent mutants were isolated. The locus for this lesion, rpiR, was mapped to 93 min on the linkage map, and the gene order zje::Tn10-rpiR-mel-zjd::Tn10-psd-purA was established. Secondly, ribose prototrophs resulted from the cloning of the rpiB gene on a multicopy plasmid. The rpiB gene resided on a 4.6-kbp HindIII-EcoRV DNA fragment from phage lambda 10H5 (642) of the Kohara gene library and mapped at 92.85 min. Consistent with this map position, the cloned DNA fragment contained two divergent open reading frames of 149 and 296 codons, encoding ribose phosphate isomerase B (molecular mass, 16,063 Da) and a negative regulator of rpiB gene expression, RpiR (molecular mass, 32,341 Da), respectively. The 5' ends of rpiB- and rpiR-specified transcripts were located by primer extension analysis. No significant amino acid sequence similarity was found between ribose phosphate isomerases A and B, but ribose phosphate isomerase B exhibited high-level similarity to both LacA and LacB subunits of the galactose 6-phosphate isomerases of several gram-positive bacteria. Analyses of strains containing rpiA, rpiB, or rpiA rpiB mutations revealed that both enzymes were equally efficient in catalyzing the isomerization step in either direction and that the construction of rpiA rpiB double mutants was a necessity to fully prevent this reaction.
Tariff structures for water and sanitation urban households: a primer

Water tariffs are a powerful management tool. Indeed, they can be seen as a conceptually simple way to promote multiple, possibly conflicting, objectives. Those trade-offs cause discrepancies between stakeholders and may produce undesirable results. The residential urban domain is particularly sensible to those predicaments. To shed some light on the matter, this paper carries out a literature survey on empirical studies, with emphasis on different tariff structures. In total, 185 publications were identified concerning the importance of tariff structures in achieving specific local objectives, or perspectives, of those who demand and supply water. These studies examine, occasionally comparing: (1) the degree to which specific objectives are achieved; (2) how the desired outcomes of a particular structure depend on the customers9 sensitivity when receiving a price signal; and (3) the drivers of the decision-makers in the tariff-setting process. A major result is the empirical evidence that the way prices are used matters almost as much as whether they are used or not.
Effect of Different Concentrations of H-NS Protein on Chromosome Replication and the Cell Cycle in Escherichia coli

ABSTRACT Flow cytometric analysis showed that the hns205 and hns206 mutants, lacking the abundant nucleoid-associated protein H-NS, have decreased origin concentration, as well as a low number of origins per cell (ploidy). The most striking observation was that the low ploidy was due to a very short replication time, e.g., at 30°C it was halved compared to that of the hns+ strain. The decreased origin concentration was not caused by a decreased dnaA gene expression, and the hns206 mutant had normal DnaA protein concentrations. The replication phenotypes of the hns206 mutant were independent of RpoS. Cells overproducing H-NS from a LacI-controlled plasmid had a normal origin concentration, indicating that H-NS is not controlling initiation. A wild-type H-NS concentration is, however, required to obtain a wild-type origin concentration, since cells with an intermediate H-NS concentration had an intermediate origin concentration. Two lines of evidence point to an indirect effect of H-NS on initiation. First, H-NS did not show high-affinity binding to any part of oriC, and H-NS had no effect on transcription entering oriC from the mioC promoter. Second, in a shift experiment with the hns206 mutant, when H-NS protein was induced to wild-type levels within 10 min, it took more than one generation before the origin concentration started to increase.
Targeting the host inflammatory response in traumatic spinal cord injury

&NA; Both acute and chronic inflammatory processes have been shown to influence outcome in experimental models of spinal cord injury. Although early inflammatory responses may participate in secondary injury processes, more delayed inflammatory events may be reparative. Therapeutic strategies that target these events are currently based on experimental findings that have clarified the cellular and molecular processes involved in the inflammatory response to injury. An increasing body of literature supports the hypothesis that acute inflammatory events are attenuated by therapeutic hypothermia and other anti‐inflammatory strategies, whereas immune neuroprotection and axonal regeneration can be achieved by transfer of activated T cells or by treatment with therapeutic vaccines. These data are summarized in the present review.
The – switch: an empirical account of the anglicisation of a Scots variant in Scotland during the sixteenth and seventeenth centuries

This article explores the anglicisation of the Scots language between the sixteenth and eighteenth centuries, focusing on the variation between the orthographic clusters and found in relative and interrogative clause markers. Using modern statistical techniques, we provide the most comprehensive empirical analysis of this variation so far in the Helsinki Corpus of Older Scots (Meurman-Solin 1995). By combining the techniques of Variability-Based Neighbour Clustering (Gries & Hilpert 2008, 2010, 2012) with mixed-effects logistic regression modelling (Baayen et al.2008), we uncover a different trajectory of change than that which has previously been reported for this feature (Meurman-Solin 1993, 1997). We argue that by using modern methods of data reduction and statistical modelling, we can present a picture of language change in Scots that is more fine-grained than previous studies which use only descriptive statistics.
Fluctuations in histone H4 isoforms during cellular reprogramming monitored by middle‐down proteomics

Cellular reprogramming remodels the gene expression program by re‐setting the epigenome of somatic cells into an embryonic‐like pluripotent state. Post‐translational modifications of histones play an important role in this process. Previously, we found by ChIP‐seq widespread changes of specific histone H3 marks in two divergent reprogramming routes leading to alternative pluripotent sates . Here, using an unbiased middle‐down proteomics approach we have identified 72 unique isoforms of histone H4 and quantified 56 of them in the same set of samples. We found substantial differences between somatic and late‐phase reprogramming cells. Also, ESCs and iPSCs displayed higher levels of H4 acetylation and tri‐methylation concomitantly with lower levels of mono‐ and di‐methylation when compared to cells undergoing reprogramming. Our data shows that the epigenetic remodeling induced by the reprogramming process goes beyond histone H3 and reveals the importance of H4 modifications as well. The presented data is a valuable resource to study the epigenetic mechanisms involved in the acquisition of induced pluripotency. All MS data have been deposited in the ProteomeXchange with identifier PXD002062 (http://proteomecentral.proteomexchange.org/dataset/PXD002062).
Prevalence of refractive errors in Möbius sequence.

PURPOSE To assess the prevalence of refractive errors in Möbius sequence. METHODS This study was carried out during the Annual Meeting of the Brazilian Möbius Society in November 2008. Forty-four patients diagnosed with the Möbius sequence were submitted to a comprehensive assessment, on the following specialties: ophthalmology, neurology, genetics, psychiatry, psychology and dentistry. Forty-three patients were cooperative and able to undertake the ophthalmological examination. Twenty-two (51.2 %) were male and 21 (48.8%) were female. The average age was 8.3 years (from 2 to 17 years). The visual acuity was evaluated using a retro-illuminated logMAR chart in cooperative patients. All children were submitted to exams on ocular motility, cyclopegic refraction, and fundus examination. RESULTS From the total of 85 eyes, using the spherical equivalent, the major of the eyes (57.6%) were emmetropics (>-0.50 D and <+2.00 D). The prevalence of astigmatism greater than or equal to 0.75 D was 40%. CONCLUSION The prevalence of refractive errors, by the spherical equivalent, was 42.4% in this studied group.
Region of interest extraction and adaptation in scalable video coding

By integrating the visual attention model in human vision system and the tile and slice group structure in scalable video coding (SVC), a novel scheme was proposed to adapt video resolution based on adaptive region of interest (AROI) extraction. This idea can be applied to ROI based video coding, adaptation and delivery, by embedding anchor point of focusing macroblock in each key frame and motion vectors (MVs) in other frames in coded video stream or sequence parameter set (SPS) in SVC.