Miracle-dz/UniFAR-FTUs huggingface dataset:
Study of Protein Phosphatase 2A (PP2A) Activity in LPS-Induced Tolerance Using Fluorescence-Based and Immunoprecipitation-Aided Methodology

Protein phosphatase 2A (PP2A) is one of the most abundant intracellular serine/threonine (Ser/Thr) phosphatases accounting for 1% of the total cellular protein content. PP2A is comprised of a heterodimeric core enzyme and a substrate-specific regulatory subunit. Potentially, at least seventy different compositions of PP2A exist because of variable regulatory subunit binding that accounts for various activity modulating numerous cell functions. Due to the constitutive phosphatase activity present inside cells, a sensitive assay is required to detect the changes of PP2A activity under various experimental conditions. We optimized a fluorescence assay (DIFMU assay) by combining it with prior anti-PP2A immunoprecipitation to quantify PP2A-specific phosphatase activity. It is also known that prior exposure to lipopolysaccharides (LPS) induces “immune tolerance” of the cells to subsequent stimulation. Herein we report that PP2A activity is upregulated in tolerized peritoneal macrophages, corresponding to decreased TNF-α secretion upon second LPS stimulation. We further examined the role of PP2A in the tolerance effect by using PP2ACαlox/lox;lyM-Cre conditional knockout macrophages. We found that PP2A phosphatase activity cannot be further increased by tolerance. TNF-α secretion from tolerized PP2ACαlox/lox;lyM-Cre macrophages is higher than tolerized control macrophages. Furthermore, we showed that the increased TNF-α secretion may be due to an epigenetic transcriptionally active signature on the promoter of TNF-α gene rather than regulation of the NFκB/IκB signaling pathway. These results suggest a role for increased PP2A activity in the regulation of immune tolerance.
All autonomy is not created equal: the countervailing effects of salesperson autonomy on burnout

Autonomy is commonly regarded as a desirable element of an employee's psychological climate that has the potential to reduce salesperson burnout. The literature is silent, however, regarding whether these beneficial effects of autonomy materialize when salespeople are tasked with making decisions that are likely to have adverse effects on the customers they serve. Building on work stress theories and data provided by a sample of 235 business-to-business (B2B) salespeople, this study posits and finds that salesperson customer relationship management (CRM) autonomy can increase or decrease salesperson burnout, depending on the nature of the CRM task at hand and prevailing conditions. To illustrate, the findings reveal that – depending on moderating factors – autonomy to create value can have a desirable or no effect on salesperson emotional exhaustion, personal accomplishment, and customer depersonalization. By contrast, the findings also reveal that autonomy to appropriate value increases emotional exhaustion among inexperienced salespeople, has mixed effects on personal accomplishment (depending on the selling time available to the salesperson), and increases customer depersonalization among salespeople who lack a customer orientation. This study underscores that, contrary to common wisdom, increasing salesperson autonomy is not a universally effective prescription for reducing salesperson burnout and its undesirable consequences.
Hashed Nonlocal Means for Rapid Image Filtering

Denoising algorithms can alleviate the trade-off between noise-level and acquisition time that still exists for certain image types. Nonlocal means, a recently proposed technique, outperforms other methods in removing noise while retaining image structure, albeit at prohibitive computational cost. Modifications have been proposed to reduce the cost, but the method is still too slow for practical filtering of 3D images. This paper proposes a hashed approach to explicitly represent two summed frequency (hash) functions of local descriptors (patches), utilizing all available image data. Unlike other approaches, the hash spaces are discretized on a regular grid, so primarily linear operations are used. The large memory requirements are overcome by recursing the hash spaces. Additional speed gains are obtained by using a marginal linear interpolation method. Careful choice of the patch features results in high computational efficiency, at similar accuracies. The proposed approach can filter a 3D image in less than a minute versus 15 minutes to 3 hours for existing nonlocal means methods.
Intrinsic Plasticity Complements Long-Term Potentiation in Parallel Fiber Input Gain Control in Cerebellar Purkinje Cells

Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at parallel fiber (PF)-to-Purkinje cell synapses can also evoke increases in intrinsic excitability. This form of intrinsic plasticity shares with LTP a requirement for the activation of protein phosphatases 1, 2A, and 2B for induction. Purkinje cell intrinsic plasticity resembles CA1 hippocampal pyramidal cell intrinsic plasticity in that it requires activity of protein kinase A (PKA) and casein kinase 2 (CK2) and is mediated by a downregulation of SK-type calcium-sensitive K conductances. In addition, Purkinje cell intrinsic plasticity similarly results in enhanced spine calcium signaling. However, there are fundamental differences: first, while in the hippocampus increases in excitability result in a higher probability for LTP induction, intrinsic plasticity in Purkinje cells lowers the probability for subsequent LTP induction. Second, intrinsic plasticity raises the spontaneous spike frequency of Purkinje cells. The latter effect does not impair tonic spike firing in the target neurons of inhibitory Purkinje cell projections in the deep cerebellar nuclei, but lowers the Purkinje cell signal-to-noise ratio, thus reducing the PF readout. These observations suggest that intrinsic plasticity accompanies LTP of active PF synapses, while it reduces at weaker, nonpotentiated synapses the probability for subsequent potentiation and lowers the impact on the Purkinje cell output.
Affectionate Communication Is Associated With Emotional and Relational Resources in the Grandparent-Grandchild Relationship

ABSTRACT Grounded in affection exchange theory (AET; Floyd, 2006), this study examined the extent to which affection received from grandparents is associated with grandchildren’s perceptions of their grandparents and their grandparent-grandchild relationship (in the form of emotional closeness, shared family identity, and perceived availability of social support). Young adult grandchildren (N = 171) completed several instruments in reference to their relationship with a specific grandparent. The results of multiple regression analyses generally supported the hypotheses that received affection is associated positively with grandchildren’s perceptions of their grandparents and their grandparent-grandchild relationship. These findings support AET’s utility in the grandparent-grandchild relationship and the notion that grandparents often influence their grandchildren’s perceptions of their family.
The Chemical Arsenal of Burkholderia pseudomallei Is Essential for Pathogenicity

Increasing evidence has shown that small-molecule chemistry in microbes (i.e., secondary metabolism) can modulate the microbe–host response in infection and pathogenicity. The bacterial disease melioidosis is conferred by the highly virulent, antibiotic-resistant pathogen Burkholderia pseudomallei (BP). Whereas some macromolecular structures have been shown to influence BP virulence (e.g., secretion systems, cellular capsule, pili), the role of the large cryptic secondary metabolome encoded within its genome has been largely unexplored for its importance to virulence. Herein we demonstrate that BP-encoded small-molecule biosynthesis is indispensible for in vivo BP pathogenicity. Promoter exchange experiments were used to induce high-level molecule production from two gene clusters (MPN and SYR) found to be essential for in vivo virulence. NMR structural characterization of these metabolites identified a new class of lipopeptide biosurfactants/biofilm modulators (the malleipeptins) and syrbactin-type proteasome inhibitors, both of which represent overlooked small-molecule virulence factors for BP. Disruption of Burkholderia virulence by inhibiting the biosynthesis of these small-molecule biosynthetic pathways may prove to be an effective strategy for developing novel melioidosis-specific therapeutics.
Fenretinide Activity in Retinoid-Resistant Oral Leukoplakia

Purpose: To test the hypothesis that the retinamide N-(4-hydroxyphenyl)retinamide (fenretinide) would be clinically active potentially via receptor-independent apoptosis and receptor-dependent effects in natural retinoid-resistant oral leukoplakia patients—the first test of this hypothesis in any in vivo setting. Experimental Design: A phase II trial of fenretinide (200 mg/d for 3 months) in oral leukoplakia patients who had not responded (de novo resistance) or who had responded and then relapsed (acquired resistance) to previous treatment with natural retinoids. We analyzed apoptosis via the terminal deoxynucleotidyl transferase–mediated nick end labeling in situ DNA fragmentation assay. Results: We accrued 35 evaluable patients with retinoid-resistant oral leukoplakia, 12 (34.3%) had partial responses to fenretinide (95% confidence interval, 19.2-52.4%), and response was associated with acquired resistance to natural retinoids (P = 0.015, Fisher's exact test). Nine responders progressed within 9 months of stopping fenretinide. Toxicity was minimal and compliance was excellent. Mean apoptosis values (SE) increased from 0.35% (0.25%) at baseline to 1.18% (0.64%) at 3 months (P = 0.001, sign test); this increase did not correlate with clinical response. The increases in 3-month mean serum concentrations of fenretinide (0.23 μmol/L) and N-(4-methoxyphenyl)retinamide (0.57 μmol/L) correlated with decreased retinol concentrations [Spearman correlation coefficient of −0.57 (P = 0.001) and −0.43 (P = 0.01), respectively]. Conclusions: Low-dose fenretinide was clinically active and produced a small increase in apoptosis in retinoid-resistant oral leukoplakia.
Eeective Metric Spaces and Representations of the Reals Preprint-reihe Mathematik 5/2000 Ernst-moritz-arndt-universitt at Greifswald Eeective Metric Spaces and Representations of the Reals

Based on standard notions of classical recursion theory, a natural model of approximate computability for partial functions between eeective metric spaces is presented. It generalizes the Ko{Friedman approach to computability of real functions by means of oracle Turing machines and avoids the explicit use of representations. The topological arithmetical hierarchy is introduced and shown to be strict if the underlying space contains an eeectively discrete sequence. The domains of computable functions are just the 2-sets of that hierarchy if the space admits a nitary stratiication. Finally, this framework is used to investigate and characterize the standard representations of the real numbers. They are just those functions from the name space onto the reals which have both computable extensions and inversions that are computable as relations.
Neural Learning Rules for the Vestibulo-Ocular Reflex

Mechanisms for the induction of motor learning in the vestibulo-ocular reflex (VOR) were evaluated by recording the patterns of neural activity elicited in the cerebellum by a range of stimuli that induce learning. Patterns of climbing-fiber, vestibular, and Purkinje cell simple-spike signals were examined during sinusoidal head movement paired with visual image movement at stimulus frequencies from 0.5 to 10 Hz. A comparison of simple-spike and vestibular signals contained the information required to guide learning only at low stimulus frequencies, and a comparison of climbing-fiber and simple-spike signals contained the information required to guide learning only at high stimulus frequencies. Learning could be guided by comparison of climbing-fiber and vestibular signals at all stimulus frequencies tested, but only if climbing fiber responses were compared with the vestibular signals present 100 msec earlier. Computational analysis demonstrated that this conclusion is valid even if there is a broad range of vestibular signals at the site of plasticity. Simulations also indicated that the comparison of vestibular and climbing-fiber signals across the 100 msec delay must be implemented by a subcellular “eligibility” trace rather than by neural circuits that delay the vestibular inputs to the site of plasticity. The results suggest two alternative accounts of learning in the VOR. Either there are multiple mechanisms of learning that use different combinations of neural signals to drive plasticity, or there is a single mechanism tuned to climbing-fiber activity that follows activity in vestibular pathways by ∼100 msec.
A Feti-dp Method for the Mortar Discretization of Elliptic Problems with Discontinuous Coefficients

Second order elliptic problems with discontinuous coefficients are considered. The problem is discretized by the finite element method on geometrically conforming non-matching triangulations across the interface using the mortar technique. The resulting discrete problem is solved by a FETI-DP method. We prove that the method is convergent and its rate of convergence is almost optimal and independent of the jumps of coefficients. Numerical experiments for the case of four subregions are reported. They confirm the theoretical results.
Collapse and expansion in the bright-rimmed cloud SFO 11NE

We report the results of a search for the double-peaked blue-skewed infall signature in the bright-rimmed cloud core SFO 11NE SMM1. Observations of the optically thick HCO + and optically thin H 13 CO + J = 3−2 lines reveal that there is indeed a characteristic double-peaked line profile, but skewed to the red rather than the blue. Modelling of the dust continuum emission and line profiles show that the motions within SFO 11NE SMM1 are consistent with a collapsing central core surrounded by an expanding outer envelope. We show that the collapse is occurring at a similar rate to that expected onto a single solar-mass protostar and is unlikely to represent the large-scale collapse of gas onto the infrared cluster seen at the heart of SFO 11NE SMM1. The outer envelope is expanding at a much greater rate than that expected for a photoevaporated flow from the cloud surface. The modelled expansion is consistent with the bulk cloud re-expansion phase predicted by radiative-driven implosion models of cometary clouds.
Predictors of mother–child interaction quality and child attachment security in at-risk families

Child healthy development is largely influenced by parent–child interaction and a secure parent–child attachment is predictively associated with positive outcomes in numerous domains of child development. However, the parent–child relationship can be affected by several psychosocial and socio-demographic risk factors that undermine its quality and in turn play a negative role in short and long term child psychological health. Prevention and intervention programs that support parenting skills in at-risk families can efficiently reduce the impact of risk factors on mother and child psychological health. This study examines predictors of mother–child interaction quality and child attachment security in a sample of first-time mothers with psychosocial and/or socio-demographic risk factors. Forty primiparous women satisfying specific risk criteria participated in a longitudinal study with their children from pregnancy until 18 month of child age. A multiple psychological and socioeconomic assessment was performed. The Emotional Availability Scales were used to measure the quality of emotional exchanges between mother and child at 12 months and the Attachment Q-Sort served as a measure of child attachment security at 18 months. Results highlight both the effect of specific single factors, considered at a continuous level, and the cumulative risk effect of different co-occurring factors, considered at binary level, on mother–child interaction quality and child attachment security. Implication for the selection of inclusion criteria of intervention programs that support parenting skills in at-risk families are discussed.
Optimal Per‐Use Rentals and Sales of Durable Products and Their Distinct Roles in Price Discrimination

We consider a setting in which consumers experience distinct instances of need for a durable product at random intervals. Each instance of need is associated with a random utility and the consumers are differentiated according to the frequency with which they experience such instances of need. We use our model of consumer utility to characterize the firm's optimal strategy of whether to sell, rent, or do a combination of both in terms of the transaction costs and consumers' usage characteristics. We find that the two modes of operation serve different roles in allowing the firm to price discriminate. While sales allow the firm to discriminate among consumers of different usage frequencies, rentals allow it to discriminate according to consumers' realized valuations. Consequently, even when transaction costs are negligible, it is often optimal for the firm to simultaneously rent and sell its product. In addition, we find that although sales and rentals are substitutes and that the offering of sales weakly increases rental prices, it is possible that the introduction of rentals to a pure selling operation can either increase or decrease the optimal sales prices.
A Two-Stage Ring Oscillator in 0 . 13-� m CMOS for UWB Impulse Radio

We present a two-stage digitally controlled ring oscillator designed mainly for impulse-radio ultra-wideband (UWB) applications. Each basic stage utilizes a local positive feedback, allowing to achieve steady oscillation at low current consumption levels, and to extend the frequency tuning over an ultra-wide range. The frequency tuning is achieved via the control of the tail resistor in each stage. The circuit is fabricated in a 0.13m CMOS technology. It features full UWB coverage at slightly higher than 1.3-V supply voltage, 121.7-dBc/Hz phase noise at a 5.6-GHz carrier, and 10-MHz offset, and less than 5-mW power consumption for the digitally controlled oscillator core alone at 10.18-GHz maximum frequency under 1.3-V supply voltage.
Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

Background. Nonalcoholic fatty liver disease (NAFLD) is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD. Aims. In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis. Methods. The concentration of fructose-drinking water (FDW) used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph. Results. After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density. Conclusion. We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.
Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection.

RATIONALE Two forms of the IFN-gamma release assay (IFNGRA) to detect tuberculosis infection are available, but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment. OBJECTIVE To compare the ability of the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold (Cellestis, Melbourne, Australia), and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons. METHODS A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha, a deprived urban South African community with an HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1,612 per 100,000. MEASUREMENTS AND MAIN RESULTS One hundred and sixty (74 HIV(+) and 86 HIV(-)) persons were enrolled. A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects (p < 0.01). By contrast, the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test (52 vs. 59%; p = 0.41) or the QuantiFERON-TB Gold test (43 and 46%; p = 0.89). Fair agreement between the Mantoux test (5- and 10-mm cutoffs) and the IFNGRA was seen in HIV-infected people (kappa = 0.52-0.6). By contrast, poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group (kappa = 0.07-0.30, depending on the Mantoux cutoff). The pattern was similar for T-SPOT.TB (kappa = 0.18-0.24). INTERPRETATION IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis.
Transforming landscapes and identities in the south Wales valleys

Abstract In contrast to the declining socio-economic legacy of the loss of coalmining and heavy industry, the landscapes of the south Wales valleys have witnessed a remarkable environmental transformation within living memory. Yet an apparent paradox exists between reported community pride in these landscapes with emerging community-led economic initiatives, and seeming indifference towards or disconnection from them. In this paper, we draw upon analysis of qualitative material from two pieces of research in different Valleys’ localities to explore landscape relationships with respect to radical landscape changes, reported disconnections and emergent community-led countryside activities. We consider these in the context of emerging models and notions of landscape identities. We conclude that the changed landscape character in the Valleys is impacting on landscape perceptions, valuation and uses with new existential identities emerging amongst some. Greater insights into evolving landscape identities might inform better land use policy and natural resource management to bring about socio-economic and environmental benefits.