Miracle-dz/UniFAR-FTUs huggingface dataset:
On the presence and role of human gene-body DNA methylation

DNA methylation of promoter sequences is a repressive epigenetic mark that down-regulates gene expression. However, DNA methylation is more prevalent within gene-bodies than seen for promoters, and gene-body methylation has been observed to be positively correlated with gene expression levels. This paradox remains unexplained, and accordingly the role of DNA methylation in gene-bodies is poorly understood. We addressed the presence and role of human gene-body DNA methylation using a meta-analysis of human genome-wide methylation, expression and chromatin data sets. Methylation is associated with transcribed regions as genic sequences have higher levels of methylation than intergenic or promoter sequences. We also find that the relationship between gene-body DNA methylation and expression levels is non-monotonic and bell-shaped. Mid-level expressed genes have the highest levels of gene-body methylation, whereas the most lowly and highly expressed sets of genes both have low levels of methylation. While gene-body methylation can be seen to efficiently repress the initiation of intragenic transcription, the vast majority of methylated sites within genes are not associated with intragenic promoters. In fact, highly expressed genes initiate the most intragenic transcription, which is inconsistent with the previously held notion that gene-body methylation serves to repress spurious intragenic transcription to allow for efficient transcriptional elongation. These observations lead us to propose a model to explain the presence of human gene-body methylation. This model holds that the repression of intragenic transcription by gene-body methylation is largely epiphenomenal, and suggests that gene-body methylation levels are predominantly shaped via the accessibility of the DNA to methylating enzyme complexes.
Alternatives in Dispute Processing: Litigation in a Small Claims Court

Social life is inevitably conflictual. Conflict occurs as individuals with different interests, goals, problems and perspectives seek to achieve a maximum share of the values which any society provides. Yet, the inevitability of conflict does not mean that its occurrence is welcomed. In fact, generally the opposite is true. Conflict, once it occurs, is difficult to end. Resolution is elusive because conflicts transform themselves almost as quickly as they can be defined and strategies for dealing with them developed.1 Nevertheless, in every society there is a wide range of techniques and procedures available to deal with disputes. Studies of the techniques and procedures employed in processing disputes typically begin by dividing them into those which require third party intervention and those which do not. The simplest and most frequently employed of these techniques do not entail third party intervention. People who are involved in conflict may take no remedial action; they may choose to "lump it" (Galanter, 1974:124-125 and Felstiner, 1974:50). Or, they may choose to "exit" from the situation in which the trouble occurs
Histamine in the basolateral amygdala promotes inhibitory avoidance learning independently of hippocampus

Significance Integrity of the brain histaminergic system is necessary for long-term memory (LTM) but not short-term memory of step-down inhibitory avoidance (IA). Histamine depletion in hippocampus or basolateral amygdala (BLA) impairs LTM of that task. Histamine infusion into either structure restores LTM in histamine-depleted rats. The restoring effect in BLA occurs even when hippocampal activity was impaired. Cyclic adenosine monophosphate (cAMP) responsive-element-binding protein phosphorylation correlates anatomically and temporally with histamine-induced memory recall. Thus, histaminergic neurotransmission appears critical to provide the brain with the plasticity necessary for IA through recruitment of alternative circuits. Our findings indicate that the histaminergic system comprises parallel, coordinated pathways that provide compensatory plasticity when one brain structure is compromised. Recent discoveries demonstrated that recruitment of alternative brain circuits permits compensation of memory impairments following damage to brain regions specialized in integrating and/or storing specific memories, including both dorsal hippocampus and basolateral amygdala (BLA). Here, we first report that the integrity of the brain histaminergic system is necessary for long-term, but not for short-term memory of step-down inhibitory avoidance (IA). Second, we found that phosphorylation of cyclic adenosine monophosphate (cAMP) responsive-element-binding protein, a crucial mediator in long-term memory formation, correlated anatomically and temporally with histamine-induced memory retrieval, showing the active involvement of histamine function in CA1 and BLA in different phases of memory consolidation. Third, we found that exogenous application of histamine in either hippocampal CA1 or BLA of brain histamine-depleted rats, hence amnesic, restored long-term memory; however, the time frame of memory rescue was different for the two brain structures, short lived (immediately posttraining) for BLA, long lasting (up to 6 h) for the CA1. Moreover, long-term memory was formed immediately after training restoring of histamine transmission only in the BLA. These findings reveal the essential role of histaminergic neurotransmission to provide the brain with the plasticity necessary to ensure memorization of emotionally salient events, through recruitment of alternative circuits. Hence, our findings indicate that the histaminergic system comprises parallel, coordinated pathways that provide compensatory plasticity when one brain structure is compromised.
The Development of the Science of Marketing—An Exploratory Survey

T HE SCIENCE or art of marketing, as we know it, has developed largely from the fields of economics, scientific management, psychology, and accounting. It is entirely possible that archeologists or historians may sometime discover that many of the principles were known and practiced by ancient peoples. But the classified body of knowledge which we call the science of marketing has evolved during the past 50 years-to a very considerable extent during the past 35 years-and it has been developed very largely by persons still living. The first college courses in marketing were offered in 1901-02 at the Universities of Illinois and Michigan. The first textbooks appeared in the years 1911 -I915. Correspondence courses in advertising were offered in Chicago in I896 by Edward T. Page and Samuel T. Davis. Harlow Gale at the University of Minnesota in the late 1890's, and Walter Dill Scott at Northwestern University by I900, devoted considerable attention to advertising in their classes in psychology, but New York University is said to have offered the first collegiate course in advertising in I9o5.1 Sooner or later studies will be made into the origins of the principles and concepts of marketing, and it seems desirable to ascertain and record the recollec-
Mineralogical and chemical characterization of lunar highland soils: Insights into the space weathering of soils on airless bodies

[1] With reflectance spectroscopy, one is measuring only properties of the fine-grained regolith most affected by space weathering. The Lunar Soil Characterization Consortium has undertaken the task of coordinated characterization of lunar soils, with respect to their mineralogical and chemical makeup. It is these lunar soils that are being used as “ground truth” for all airless bodies. Modal abundances and chemistries of minerals and glasses in the finest size fractions (20–45, 10–20, and <10 μm) of four Apollo 14 and six Apollo 16 highland soils have been determined, as well as their bulk chemistry and IS/FeO values. Bidirectional reflectance measurements (0.3–2.6 μm) of all samples were performed in the Reflectance Experiment Laboratory. A significant fraction of nanophase Fe0 (np-Fe0) appears to reside in agglutinitic glasses. However, as grain size of a soil decreases, the percentage of total iron present as np-Fe0 increases significantly, whereas the agglutinitic glass content rises only slightly; this is evidence for a large contribution to the IS/FeO values from the surface-correlated nanophase Fe0, particularly in the <10 μm size fraction. The compositions of the agglutinitic glasses in these fine fractions of the highland soils are different from the bulk chemistry of that size; however, compositional trends of the glasses are not the same as those observed for mare soils. It is apparent that the glasses in the highland soils contain chemical components from outside their terrains. It is proposed that the Apollo 16 soils have been adulterated by the addition of impact-transported soil components from surrounding maria.
Notching on Cancer’s Door: Notch Signaling in Brain Tumors

Notch receptors play an essential role in the regulation of central cellular processes during embryonic and postnatal development. The mammalian genome encodes for four Notch paralogs (Notch 1–4), which are activated by three Delta-like (Dll1/3/4) and two Serrate-like (Jagged1/2) ligands. Further, non-canonical Notch ligands such as epidermal growth factor like protein 7 (EGFL7) have been identified and serve mostly as antagonists of Notch signaling. The Notch pathway prevents neuronal differentiation in the central nervous system by driving neural stem cell maintenance and commitment of neural progenitor cells into the glial lineage. Notch is therefore often implicated in the development of brain tumors, as tumor cells share various characteristics with neural stem and progenitor cells. Notch receptors are overexpressed in gliomas and their oncogenicity has been confirmed by gain- and loss-of-function studies in vitro and in vivo. To this end, special attention is paid to the impact of Notch signaling on stem-like brain tumor-propagating cells as these cells contribute to growth, survival, invasion, and recurrence of brain tumors. Based on the outcome of ongoing studies in vivo, Notch-directed therapies such as γ-secretase inhibitors and blocking antibodies have entered and completed various clinical trials. This review summarizes the current knowledge on Notch signaling in brain tumor formation and therapy.
Moderate and Severe Blood Pressure Elevation Associated with Stroke in the Mexican Hispanic Population

Background: Stroke is the fourth leading cause of death in US. Amongst other factors such as age, sex, race, genetics, obesity, diabetes etc., hypertension continues to be the leading contributing factor towards stroke. Studies regarding stroke in Hispanics are sparse and inconclusive. Objectives: The objective of the present study is to investigate the potential association between blood pressure elevation and risk of ischemic stroke among the Mexican Hispanic population. Methods: A retrospective data analysis was carried out for a planned case-control study with case-control ratios of 1:2. Mexican Hispanic cases were from the ElPasoStroke database with diagnosed hypertension that had sustained an ischemic stroke (n = 505) and Mexican Hispanics diagnosed with hypertension who were stroke-free as controls from the 2005–2010 NHANES databases (n = 1010). In this analysis, we included subjects who had data on systolic, diastolic or mean arterial blood pressures for cases (327) and controls (772). In cases, blood pressure was determined by the initial admission measurement, and in controls, the first measured blood pressure was used. The unadjusted and adjusted effects of continuous measurements of systolic, diastolic and mean arterial blood pressure on stroke were determined using logistic regression analyses. Subjects were further classified into groups based on prehypertension and hypertension ranges, as established by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). Unadjusted and adjusted logistic regression models were also used to determine the effect of categorized blood pressures. Results: Our data indicate that per unit increase in systolic, diastolic or mean arterial blood pressure elevates the odds of stroke among the Mexican Hispanic population. Adjusted analysis of categorized blood pressures showed that mild or moderate/severe high blood pressure significantly associated with odds of stroke. Maintaining and controlling blood pressure at more stringent and lower levels, specifically lowering mean arterial pressure may effectively reduce the odds of ischemic stroke among the Mexican Hispanic population. Conclusion: Elevation of blood pressure increases the odds of stroke among the Mexican Hispanic population. Our results provide new strategies to manage the stroke prevention and health disparity issues among the Mexican Hispanic population.
Cochlear implants in children : development in interaction with the social context

Between 150 and 200 deaf children are born in the Netherlands each year. Deafness has major consequences for these children’s development, as it deprives them of access to spoken language. Since the 1990s, deaf children have been able to have a cochlear implant (CI), which enables them to experience sound. The questions central to this thesis concern the way in which a CI affects children’s development, and the factors that play an important role in this. The framework for this thesis is provided by Bronfenbrenner’s social-ecological model, which proposes that children’s development is influenced by the quality and quantity of their interpersonal interactions. These interactions are influenced indirectly by the environment in which children live. In young children with a CI, language development and the social-emotional development are both delayed compared to their hearing peers. However, it is not yet cl ear how these children will develop in the future. The children who participated in this study were still very young, and a number of them received their CI relatively late. It is possible that they will catch up with hearing children when they are older and have had a longer period of access to spoken language.
A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults

Background Strategies to enhance the immunogenicity of DNA vaccines in humans include i) co-administration of molecular adjuvants, ii) intramuscular administration followed by in vivo electroporation (IM/EP) and/or iii) boosting with a different vaccine. Combining these strategies provided protection of macaques challenged with SIV; this clinical trial was designed to mimic the vaccine regimen in the SIV study. Methods Seventy five healthy, HIV-seronegative adults were enrolled into a phase 1, randomized, double-blind, placebo-controlled trial. Multi-antigenic HIV (HIVMAG) plasmid DNA (pDNA) vaccine alone or co-administered with pDNA encoding human Interleukin 12 (IL-12) (GENEVAX IL-12) given by IM/EP using the TriGrid Delivery System was tested in different prime-boost regimens with recombinant Ad35 HIV vaccine given IM. Results All local reactions but one were mild or moderate. Systemic reactions and unsolicited adverse events including laboratory abnormalities did not differ between vaccine and placebo recipients. No serious adverse events (SAEs) were reported. T cell and antibody response rates after HIVMAG (x3) prime—Ad35 (x1) boost were independent of IL-12, while the magnitude of interferon gamma (IFN-γ) ELISPOT responses was highest after HIVMAG (x3) without IL-12. The quality and phenotype of T cell responses shown by intracellular cytokine staining (ICS) were similar between groups. Inhibition of HIV replication by autologous T cells was demonstrated after HIVMAG (x3) prime and was boosted after Ad35. HIV specific antibodies were detected only after Ad35 boost, although there was a priming effect with 3 doses of HIVMAG with or without IL-12. No anti-IL-12 antibodies were detected. Conclusion The vaccines were safe, well tolerated and moderately immunogenic. Repeated administration IM/EP was well accepted. An adjuvant effect of co-administered plasmid IL-12 was not detected. Trial Registration ClinicalTrials.gov NCT01496989
White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?

IMPORTANCE Current hypothetical models emphasize the importance of β-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation. OBJECTIVE To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography-derived amyloid positivity on the clinical expression of AD. DESIGN Baseline PIB-positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59). SETTING The Alzheimer's Disease Neuroimaging Initiative public database. PARTICIPANTS The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database. MAIN OUTCOME MEASURES Clinical AD diagnosis and WMH volume. RESULTS Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD. CONCLUSIONS AND RELEVANCE White matter hyperintensities contribute to the presentation of AD and, in the context of significant amyloid deposition, may provide a second hit necessary for the clinical manifestation of the disease. As risk factors for the development of WMHs are modifiable, these findings suggest intervention and prevention strategies for the clinical syndrome of AD.
The Human Nasal Microbiota and Staphylococcus aureus Carriage

Background Colonization of humans with Staphylococcus aureus is a critical prerequisite of subsequent clinical infection of the skin, blood, lung, heart and other deep tissues. S. aureus persistently or intermittently colonizes the nares of ∼50% of healthy adults, whereas ∼50% of the general population is rarely or never colonized by this pathogen. Because microbial consortia within the nasal cavity may be an important determinant of S. aureus colonization we determined the composition and dynamics of the nasal microbiota and correlated specific microorganisms with S. aureus colonization. Methodology/Principal Findings Nasal specimens were collected longitudinally from five healthy adults and a cross-section of hospitalized patients (26 S. aureus carriers and 16 non-carriers). Culture-independent analysis of 16S rRNA sequences revealed that the nasal microbiota of healthy subjects consists primarily of members of the phylum Actinobacteria (e.g., Propionibacterium spp. and Corynebacterium spp.), with proportionally less representation of other phyla, including Firmicutes (e.g., Staphylococcus spp.) and Proteobacteria (e.g. Enterobacter spp). In contrast, inpatient nasal microbiotas were enriched in S. aureus or Staphylococcus epidermidis and diminished in several actinobacterial groups, most notably Propionibacterium acnes. Moreover, within the inpatient population S. aureus colonization was negatively correlated with the abundances of several microbial groups, including S. epidermidis (p = 0.004). Conclusions/Significance The nares environment is colonized by a temporally stable microbiota that is distinct from other regions of the integument. Negative association between S. aureus, S. epidermidis, and other groups suggests microbial competition during colonization of the nares, a finding that could be exploited to limit S. aureus colonization.
Reputation of Communities of Web Services - Preliminary Investigation

Web services communities can be seen as virtual clusters that agglomerate Web services with the same functionality (e.g., FlightBooking). However, selecting a community to deal with is a challenging task to users and providers. Reputation, besides other selection criteria, has been widely used for evaluating and ranking candidates. Interestingly, the definition of community reputation from the perspective of users differs from the perspective of Web service providers. In this paper, we introduce a reputation-based Web services community architecture and define some of the performance metrics that are needed to assess the reputation of a Web service community as perceived by users and providers.
Empowerment and performance of managers and subordinates in elderly care: A longitudinal and multilevel study

AIM To investigate relationships between first-line managers' ratings of structural and psychological empowerment, and the subordinates' ratings of structural empowerment, as well as their ratings of the managers' leadership-management performance. BACKGROUND Work situations in elderly care are complex. To date, few studies have used a longitudinal, correlational and multilevel design to study the working life of subordinates and managers. METHOD In five Swedish municipalities, questionnaires were answered twice during 2010-12 by 56 first-line managers and 769 subordinates working in nursing homes or home-help services. RESULTS First-line managers' empowerment at Time 1 partially predicted subordinate's structural empowerment and ratings of their managers' leadership-management performance at Time 2. Changes over time partially revealed that the more access managers had to structural empowerment, i.e. increase over time, the higher the ratings were for structural empowerment and managerial leadership-management performance among subordinates. CONCLUSIONS Findings strengthen research and theoretical suggestions linking first-line managers' structural empowerment to their subordinates' structural empowerment and ratings of their manager's leadership-management performance. IMPLICATIONS FOR NURSING MANAGEMENT Managers with high access to structural empowerment are more likely to provide subordinates access to structural empowerment.