ChREBP regulates fructose-induced glucose production independently of insulin signaling

PubMed Central

Kim, Mi-Sung; Krawczyk, Sarah A.; Doridot, Ludivine; Fowler, Alan J.; Wang, Jennifer X.; Trauger, Sunia A.; Noh, Hye-Lim; Kang, Hee Joon; Meissen, John K.; Blatnik, Matthew; Kim, Jason K.; Lai, Michelle; Herman, Mark A.

2016-01-01

Obese, insulin-resistant states are characterized by a paradoxical pathogenic condition in which the liver appears to be selectively insulin resistant. Specifically, insulin fails to suppress glucose production, yet successfully stimulates de novo lipogenesis. The mechanisms underlying this dysregulation remain controversial. Here, we hypothesized that carbohydrate-responsive element-binding protein (ChREBP), a transcriptional activator of glycolytic and lipogenic genes, plays a central role in this paradox. Administration of fructose increased hepatic hexose-phosphate levels, activated ChREBP, and caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hepatic steatosis in mice. Activation of ChREBP was required for the increased expression of glycolytic and lipogenic genes as well as glucose-6-phosphatase (G6pc) that was associated with the effects of fructose administration. We found that fructose-induced G6PC activity is a major determinant of hepatic glucose production and reduces hepatic glucose-6-phosphate levels to complete a homeostatic loop. Moreover, fructose activated ChREBP and induced G6pc in the absence of Foxo1a, indicating that carbohydrate-induced activation of ChREBP and G6PC dominates over the suppressive effects of insulin to enhance glucose production. This ChREBP/G6PC signaling axis is conserved in humans. Together, these findings support a carbohydrate-mediated, ChREBP-driven mechanism that contributes to hepatic insulin resistance. PMID:27669460

Network-specific mechanisms may explain the paradoxical effects of carbamazepine and phenytoin.

PubMed

Thomas, Evan A; Petrou, Steven

2013-07-01

A common notion of the mechanism by which the antiepileptic drugs (AEDs) carbamazepine and phenytoin act is that they block sodium channels by binding preferentially to the inactivated state, thereby allowing normal neuronal firing while blocking ictal activity. However, these drugs have unpredictable efficacy and, in some cases, may exacerbate seizures. Previous studies have suggested that reducing sodium channel availability in the dentate gyrus (DG) paradoxically increases excitability. We used a biophysically detailed computer model of the DG to test the hypothesis that AEDs increase excitability by disproportionately reducing negative feedback mechanisms. We built a Markov model of sodium channel gating that reproduces responses to voltage clamp experiments in the presence of carbamazepine and phenytoin. We incorporated this validated Markov model into a biophysically realistic computer model of DG neurons and networks. Simulated drug concentrations were similar to those measured in cerebral spinal fluid in medicated patients. Single neuron models were stimulated with current injections, and networks were stimulated with perforant path synaptic input. In the network model, environmental effects were studied by introducing mossy fiber sprouting. As expected, drugs reduced sodium channel availability, which in turn reduced action potential amplitude. This had only a small effect on action potential (AP) firing rate during brief (100 msec) current injections. Paradoxically, long current injections (2,500 msec) increased AP firing rates. This was caused by reduced calcium entry and consequently reduced activation of calcium activated potassium channels. It is important to note that the main determinant of drug effect was resting membrane potential (RMP) and not action potential firing rate. Binding of phenytoin and carbamazepine is slow and, thus drug effects are largely determined by the long term state of the RMP. This paradoxical AP firing increase was dependent on the unusually large calcium-activated potassium conductances expressed by DG granule cells. This predicts that drug efficacy in a given network will depend on the precise makeup of conductances in the network. RMP is expected to vary with the level of activity in the network. We simulated the effects of drugs on single shot stimulus responses in networks with mossy fiber sprouting and varied the RMP in all neurons as a model for network activity. For an RMP of -50 mV, representing an active network, drugs had no effect, or in some cases, increased excitability. Drugs had an increasingly larger inhibitory effect on network responses as RMP decreased. An important prediction is that drugs will be unable to block ictal activity invading an active network. Our key findings are that drug effects depend on both intrinsic properties of the network and its behavioral state. This may explain the paradoxical and unpredictable effects of some AEDs on seizure control in some patients. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

PubMed Central

Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

2013-01-01

Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism. PMID:23365169

Chasing our tails: psychological, institutional and societal paradoxes in natural resource management, sustainability, and climate change in Australia.

PubMed

Browne, A L; Bishop, B J

2011-06-01

Natural Resource Management (NRM) and Ecologically Sustainable Development (ESD) have been guiding frameworks in Australia for a number of decades. Recently, NRM and ESD have become central to climate change mitigation. In this paper, we explore the psychological paradoxes that function within climate change settings, with particular attention devoted to the way that research and development reinforces these paradoxes by advocating for participatory forms of inquiry. Paradox emerges in NRM at psychological, institutional, and organisational levels. Paradoxes are also features of different forms of democracy such as neoliberal and participatory democracy. Although NRM, ESD and climate change are often conceptualised as distinct issue domains, these policy areas are fundamentally interconnected in both theory and in practice. This interconnection between these policy and research settings, reflections on paradox, and the experience of incorporating community psychology into the paradoxical settings of NRM and climate change are captured in this paper.

Coiled-coil destabilizing residues in the group A Streptococcus M1 protein are required for functional interaction.

PubMed

Stewart, Chelsea M; Buffalo, Cosmo Z; Valderrama, J Andrés; Henningham, Anna; Cole, Jason N; Nizet, Victor; Ghosh, Partho

2016-08-23

The sequences of M proteins, the major surface-associated virulence factors of the widespread bacterial pathogen group A Streptococcus, are antigenically variable but have in common a strong propensity to form coiled coils. Paradoxically, these sequences are also replete with coiled-coil destabilizing residues. These features are evident in the irregular coiled-coil structure and thermal instability of M proteins. We present an explanation for this paradox through studies of the B repeats of the medically important M1 protein. The B repeats are required for interaction of M1 with fibrinogen (Fg) and consequent proinflammatory activation. The B repeats sample multiple conformations, including intrinsically disordered, dissociated, as well as two alternate coiled-coil conformations: a Fg-nonbinding register 1 and a Fg-binding register 2. Stabilization of M1 in the Fg-nonbinding register 1 resulted in attenuation of Fg binding as expected, but counterintuitively, so did stabilization in the Fg-binding register 2. Strikingly, these register-stabilized M1 proteins gained the ability to bind Fg when they were destabilized by a chaotrope. These results indicate that M1 stability is antithetical to Fg interaction and that M1 conformational dynamics, as specified by destabilizing residues, are essential for interaction. A "capture-and-collapse" model of association accounts for these observations, in which M1 captures Fg through a dynamic conformation and then collapses into a register 2-coiled coil as a result of stabilization provided by binding energy. Our results support the general conclusion that destabilizing residues are evolutionarily conserved in M proteins to enable functional interactions necessary for pathogenesis.

Evolutionary transitions to new DNA methyltransferases through target site expansion and shrinkage.

PubMed

Rockah-Shmuel, Liat; Tawfik, Dan S

2012-12-01

DNA-binding and modifying proteins show high specificity but also exhibit a certain level of promiscuity. Such latent promiscuous activities comprise the starting points for new protein functions, but this hypothesis presents a paradox: a new activity can only evolve if it already exists. How then, do novel activities evolve? DNA methyltransferases, for example, are highly divergent in their target sites, but how transitions toward novel sites occur remains unknown. We performed laboratory evolution of the DNA methyltransferase M.HaeIII. We found that new target sites emerged primarily through expansion of the original site, GGCC, and the subsequent shrinkage of evolved expanded sites. Variants evolved for sites that are promiscuously methylated by M.HaeIII [GG((A)/(T))CC and GGCGCC] carried mutations in 'gate-keeper' residues. They could thereby methylate novel target sites such as GCGC and GGATCC that were neither selected for nor present in M.HaeIII. These 'generalist' intermediates were further evolved to obtain variants with novel target specificities. Our results demonstrate the ease by which new DNA-binding and modifying specificities evolve and the mechanism by which they occur at both the protein and DNA levels.

Paradoxical (REM) sleep deprivation in mice using the small-platforms-over-water method: polysomnographic analyses and melanin-concentrating hormone and hypocretin/orexin neuronal activation before, during and after deprivation.

PubMed

Arthaud, Sebastien; Varin, Christophe; Gay, Nadine; Libourel, Paul-Antoine; Chauveau, Frederic; Fort, Patrice; Luppi, Pierre-Herve; Peyron, Christelle

2015-06-01

Studying paradoxical sleep homeostasis requires the specific and efficient deprivation of paradoxical sleep and the evaluation of the subsequent recovery period. With this aim, the small-platforms-over-water technique has been used extensively in rats, but only rare studies were conducted in mice, with no sleep data reported during deprivation. Mice are used increasingly with the emergence of transgenic mice and technologies such as optogenetics, raising the need for a reliable method to manipulate paradoxical sleep. To fulfil this need, we refined this deprivation method and analysed vigilance states thoroughly during the entire protocol. We also studied activation of hypocretin/orexin and melanin-concentrating hormone neurones using Fos immunohistochemistry to verify whether mechanisms regulating paradoxical sleep in mice are similar to those in rats. We showed that 48 h of deprivation was highly efficient, with a residual amount of paradoxical sleep of only 2.2%. Slow wave sleep and wake quantities were similar to baseline, except during the first 4 h of deprivation, where slow wave sleep was strongly reduced. After deprivation, we observed a 124% increase in paradoxical sleep quantities during the first hour of rebound. In addition, 34% of hypocretin/orexin neurones were activated during deprivation, whereas melanin-concentrated hormone neurones were activated only during paradoxical sleep rebound. Corticosterone level showed a twofold increase after deprivation and returned to baseline level after 4 h of recovery. In summary, a fairly selective deprivation and a significant rebound of paradoxical sleep can be obtained in mice using the small-platforms-over-water method. As in rats, rebound is accompanied by a selective activation of melanin-concentrating hormone neurones. © 2014 European Sleep Research Society.

The DnaK Chaperone Uses Different Mechanisms To Promote and Inhibit Replication of Vibrio cholerae Chromosome 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jha, Jyoti K.; Li, Mi; Ghirlando, Rodolfo

Replication of Vibrio cholerae chromosome 2 (Chr2) depends on molecular chaperone DnaK to facilitate binding of the initiator (RctB) to the replication origin. The binding occurs at two kinds of site, 12-mers and 39-mers, which promote and inhibit replication, respectively. Here we show that DnaK employs different mechanisms to enhance the two kinds of binding. We found that mutations inrctBthat reduce DnaK binding also reduce 12-mer binding and initiation. The initiation defect is suppressed by second-site mutations that increase 12-mer binding only marginally. Instead, they reduce replication inhibitory mechanisms: RctB dimerization and 39-mer binding. One suppressing change was in amore » dimerization domain which is folded similarly to the initiator of an iteron plasmid—the presumed progenitor of Chr2. In plasmids, DnaK promotes initiation by reducing dimerization. A different mutation was in the 39-mer binding domain of RctB and inactivated it, indicating an alternative suppression mechanism. Paradoxically, although DnaK increases 39-mer binding, the increase was also achieved by inactivating the DnaK binding site of RctB. This result suggests that the site inhibits the 39-mer binding domain (via autoinhibition) when prevented from binding DnaK. Taken together, our results reveal an important feature of the transition from plasmid to chromosome: the Chr2 initiator retains the plasmid-like dimerization domain and its control by chaperones but uses the chaperones in an unprecedented way to control the inhibitory 39-mer binding. IMPORTANCE The capacity of proteins to undergo remodeling provides opportunities to control their function. However, remodeling remains a poorly understood aspect of the structure-function paradigm due to its dynamic nature. Here we have studied remodeling of the initiator of replication ofVibrio choleraeChr2 by the molecular chaperone, DnaK. We show that DnaK binds to a site on the Chr2 initiator (RctB) that promotes initiation by reducing the initiator’s propensity to dimerize. Dimerization of the initiator of the putative plasmid progenitor of Chr2 is also reduced by DnaK, which promotes initiation. Paradoxically, the DnaK binding also promotes replication inhibition by reducing an autoinhibitory activity of RctB. In the plasmid-to-chromosome transition, it appears that the initiator has acquired an autoinhibitory activity and along with it a new chaperone activity that apparently helps to control replication inhibition independently of replication promotion.« less

Paradoxical behavior of neuromedin U in isolated smooth muscle cells and intact tissue.

PubMed

Brighton, Paul J; Wise, Alan; Dass, Narinder B; Willars, Gary B

2008-04-01

Neuromedin U (NmU) is a neuropeptide showing high levels of structural conservation across different species. Since its discovery in 1985, NmU has been implicated in numerous physiological roles, including smooth muscle contraction, energy homeostasis, stress, intestinal ion transport, pronociception, and circadian rhythm. Two G-protein-coupled receptors have been identified for NmU and cloned from humans, rats, and mice. Recombinantly expressed NmU receptors couple to both Galpha(q/11) and Galpha(i) G-proteins, and NmU binds essentially irreversibly, preventing signaling to repetitive applications of NmU. However, it is unclear whether these properties reflect those of endogenously expressed NmU receptors or how these properties influence the functional consequences of NmU receptor signaling. Here, we have explored the signaling by rat NmU receptors expressed endogenously in cultured rat colonic smooth muscle cells and explore the functional consequence of this signaling by investigating the NmU-mediated contraction of ex vivo rat colonic smooth muscle preparations. We demonstrate that endogenous rat NmU receptors couple to both Galpha(q/11) and Galpha(i) G-proteins. Furthermore, we show complex patterns of Ca(2+) signaling, including oscillations, and provide evidence of essentially irreversible binding of NmU to smooth muscle cells. Challenge of either circular or longitudinal rat isolated colonic smooth muscle preparations with NmU resulted in robust contractions. Stimulation was direct, and paradoxically, repetitive applications of NmU mediated repetitive contractions with no evidence of desensitization, highlighting a major discrepancy in the behavior of NmU in single cells and in intact tissues. The reason for this discrepancy is presently unknown.

Tofacitinib restores the inhibition of reverse cholesterol transport induced by inflammation: understanding the lipid paradox associated with rheumatoid arthritis.

PubMed

Pérez-Baos, S; Barrasa, J I; Gratal, P; Larrañaga-Vera, A; Prieto-Potin, I; Herrero-Beaumont, G; Largo, R

2017-09-01

Patients with active rheumatoid arthritis (RA) have increased cardiovascular mortality, paradoxically associated with reduced circulating lipid levels. The JAK inhibitor tofacitinib ameliorates systemic and joint inflammation in RA with a concomitant increase in serum lipids. We analysed the effect of tofacitinib on the lipid profile of hyperlipidaemic rabbits with chronic arthritis (CA) and on the changes in reverse cholesterol transport (RCT) during chronic inflammation. CA was induced in previously immunized rabbits, fed a high-fat diet, by administering four intra-articular injections of ovalbumin. A group of rabbits received tofacitinib (10 mg·kg -1 ·day -1 ) for 2 weeks. Systemic and synovial inflammation and lipid content were evaluated. For in vitro studies, THP-1-derived macrophages were exposed to high lipid concentrations and then stimulated with IFNγ in the presence or absence of tofacitinib in order to study mediators of RCT. Tofacitinib decreased systemic and synovial inflammation and increased circulating lipid levels. Although it did not modify synovial macrophage density, it reduced the lipid content within synovial macrophages. In foam macrophages in culture, IFNγ further stimulated intracellular lipid accumulation, while the JAK/STAT inhibition provoked by tofacitinib induced lipid release by increasing the levels of cellular liver X receptor α and ATP-binding cassette transporter (ABCA1) synthesis. Active inflammation could be associated with lipid accumulation within macrophages of CA rabbits. JAK inhibition induced lipid release through RCT activation, providing a plausible explanation for the effect of tofacitinib on the lipid profile of RA patients. © 2017 The British Pharmacological Society.

PRDM9 Drives Evolutionary Erosion of Hotspots in Mus musculus through Haplotype-Specific Initiation of Meiotic Recombination

PubMed Central

Baker, Christopher L.; Kajita, Shimpei; Walker, Michael; Saxl, Ruth L.; Raghupathy, Narayanan; Choi, Kwangbom; Petkov, Petko M.; Paigen, Kenneth

2015-01-01

Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured activity of the Prdm9 Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced experimentally. Comparing these two strains, we find that haplotype differences at hotspots lead to qualitative and quantitative changes in PRDM9 binding and activity. Using Mus spretus as an outlier, we found most variants affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing hotspot activity. Furthermore, M.m. castaneus×M.m. domesticus F1 hybrids exhibit novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin modification. These novel hotspots represent sites of historic evolutionary erosion that become activated in hybrids due to crosstalk between one parent's Prdm9 allele and the opposite parent's chromosome. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion. PMID:25568937

PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination.

PubMed

Baker, Christopher L; Kajita, Shimpei; Walker, Michael; Saxl, Ruth L; Raghupathy, Narayanan; Choi, Kwangbom; Petkov, Petko M; Paigen, Kenneth

2015-01-01

Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced experimentally. Comparing these two strains, we find that haplotype differences at hotspots lead to qualitative and quantitative changes in PRDM9 binding and activity. Using Mus spretus as an outlier, we found most variants affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing hotspot activity. Furthermore, M.m. castaneus×M.m. domesticus F1 hybrids exhibit novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin modification. These novel hotspots represent sites of historic evolutionary erosion that become activated in hybrids due to crosstalk between one parent's Prdm9 allele and the opposite parent's chromosome. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion.

Effect of MUC1 Expression on EGFR Endocytosis and Degradation in Human Breast Cancer Cell Lines

DTIC Science & Technology

2007-04-01

AR), heparin-binding EGF (HB-EGF), betacellulin (BTC), epiregulin ( EPR ), and epigen [reviewed in (Schroeder & Lee, 1997) and (Strachan et al., 2001...of erbB1, it also promotes its internalization. This apparent paradox may be explained by one of two non-exclusive hypotheses. The first is that

An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L.

PubMed

Favale, Fabrizia; Messaoudi, Kahia; Varghese, Leila N; Boukour, Siham; Pecquet, Christian; Gryshkova, Vitalina; Defour, Jean Philippe; Albu, Roxana-Irina; Bluteau, Olivier; Ballerini, Paola; Leverger, Guy; Plo, Isabelle; Debili, Najet; Raslova, Hana; Favier, Remi; Constantinescu, Stefan N; Vainchenker, William

2016-12-29

The mechanisms behind the hereditary thrombocytosis induced by the thrombopoietin (THPO) receptor MPL P106L mutant remain unknown. A complete trafficking defect to the cell surface has been reported, suggesting either weak constitutive activity or nonconventional THPO-dependent mechanisms. Here, we report that the thrombocytosis phenotype induced by MPL P106L belongs to the paradoxical group, where low MPL levels on platelets and mature megakaryocytes (MKs) lead to high serum THPO levels, whereas weak but not absent MPL cell-surface localization in earlier MK progenitors allows response to THPO by signaling and amplification of the platelet lineage. MK progenitors from patients showed no spontaneous growth and responded to THPO, and MKs expressed MPL on their cell surface at low levels, whereas their platelets did not respond to THPO. Transduction of MPL P106L in CD34 + cells showed that this receptor was more efficiently localized at the cell surface on immature than on mature MKs, explaining a proliferative response to THPO of immature cells and a defect in THPO clearance in mature cells. In a retroviral mouse model performed in Mpl -/- mice, MPL P106L could induce a thrombocytosis phenotype with high circulating THPO levels. Furthermore, we could select THPO-dependent cell lines with more cell-surface MPL P106L localization that was detected by flow cytometry and [ 125 I]-THPO binding. Altogether, these results demonstrate that MPL P106L is a receptor with an incomplete defect in trafficking, which induces a low but not absent localization of the receptor on cell surface and a response to THPO in immature MK cells. © 2016 by The American Society of Hematology.

The hypomethylating agent Decitabine causes a paradoxical increase in 5-hydroxymethylcytosine in human leukemia cells

PubMed Central

Chowdhury, Basudev; McGovern, Andrew; Cui, Yi; Choudhury, Samrat Roy; Cho, Il-Hoon; Cooper, Bruce; Chevassut, Timothy; Lossie, Amy C.; Irudayaraj, Joseph

2015-01-01

The USFDA approved “epigenetic drug”, Decitabine, exerts its effect by hypomethylating DNA, demonstrating the pivotal role aberrant genome-wide DNA methylation patterns play in cancer ontology. Using sensitive technologies in a cellular model of Acute Myeloid Leukemia, we demonstrate that while Decitabine reduces the global levels of 5-methylcytosine (5mC), it results in paradoxical increase of 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels. Hitherto, the only biological mechanism known to generate 5hmC, 5fC and 5caC, involving oxidation of 5mC by members of Ten-Eleven-Translocation (TET) dioxygenase family, was not observed to undergo any alteration during DAC treatment. Using a multi-compartmental model of DNA methylation, we show that partial selectivity of TET enzymes for hemi-methylated CpG dinucleotides could lead to such alterations in 5hmC content. Furthermore, we investigated the binding of TET1-catalytic domain (CD)-GFP to DNA by Fluorescent Correlation Spectroscopy in live cells and detected the gradual increase of the DNA bound fraction of TET1-CD-GFP after treatment with Decitabine. Our study provides novel insights on the therapeutic activity of DAC in the backdrop of the newly discovered derivatives of 5mC and suggests that 5hmC has the potential to serve as a biomarker for monitoring the clinical success of patients receiving DAC. PMID:25901663

The influence of tumor oxygenation on hypoxia imaging in murine squamous cell carcinoma using [64Cu]Cu-ATSM or [18F]Fluoromisonidazole positron emission tomography.

PubMed

Matsumoto, Ken-Ichiro; Szajek, Lawrence; Krishna, Murali C; Cook, John A; Seidel, Jurgen; Grimes, Kelly; Carson, Joann; Sowers, Anastasia L; English, Sean; Green, Michael V; Bacharach, Stephen L; Eckelman, William C; Mitchell, James B

2007-04-01

[64Cu]Cu(II)-ATSM (64Cu-ATSM) and [18F]-Fluoromisonidazole (18F-FMiso) tumor binding as assessed by positron emisson topography (PET) was used to determine the responsiveness of each probe to modulation in tumor oxygenation levels in the SCCVII tumor model. Animals bearing the SCCVII tumor were injected with 64Cu-ATSM or 18F-FMiso followed by dynamic small animal PET imaging. Animals were imaged with both agents using different inspired oxygen mixtures (air, 10% oxygen, carbogen) which modulated tumor hypoxia as independently assessed by the hypoxia marker pimonidazole. The extent of hypoxia in the SCCVII tumor as monitored by the pimonidazole hypoxia marker was found to be in the following order: 10% oxygen>air>carbogen. Tumor uptake of 64Cu-ATSM could not be changed if the tumor was oxygenated using carbogen inhalation 90 min post-injection suggesting irreversible cellular uptake of the 64Cu-ATSM complex. A small but significant paradoxical increase in 64Cu-ATSM tumor uptake was observed for animals breathing air or carbogen compared to 10% oxygen. There was a positive trend toward 18F-FMiso tumor uptake as a function of changing hypoxia levels in agreement with the pimonidazole data. 64Cu-ATSM tumor uptake was unable to predictably detect changes in varying amounts of hypoxia when oxygenation levels in SCCVII tumors were modulated. 18F-FMiso tumor uptake was more responsive to changing levels of hypoxia. While the mechanism of nitroimidazole binding to hypoxic cells has been extensively studied, the avid binding of Cu-ATSM to tumors may involve other mechanisms independent of hypoxia that warrant further study.

Qualities and Inequalities in Online Social Networks through the Lens of the Generalized Friendship Paradox.

PubMed

Momeni, Naghmeh; Rabbat, Michael

2016-01-01

The friendship paradox is the phenomenon that in social networks, people on average have fewer friends than their friends do. The generalized friendship paradox is an extension to attributes other than the number of friends. The friendship paradox and its generalized version have gathered recent attention due to the information they provide about network structure and local inequalities. In this paper, we propose several measures of nodal qualities which capture different aspects of their activities and influence in online social networks. Using these measures we analyse the prevalence of the generalized friendship paradox over Twitter and we report high levels of prevalence (up to over 90% of nodes). We contend that this prevalence of the friendship paradox and its generalized version arise because of the hierarchical nature of the connections in the network. This hierarchy is nested as opposed to being star-like. We conclude that these paradoxes are collective phenomena not created merely by a minority of well-connected or high-attribute nodes. Moreover, our results show that a large fraction of individuals can experience the generalized friendship paradox even in the absence of a significant correlation between degrees and attributes.

"Coming to a 'Place' near You?" The Politics and Possibilities of a Critical Pedagogy of Place-Based Education

ERIC Educational Resources Information Center

McInerney, Peter; Smyth, John; Down, Barry

2011-01-01

It may seem something of a paradox that in a globalised age where notions of interdependence, interconnectedness and common destinies abound, the "local", with its diversity of cultures, languages, histories and geographies, continues to exercise a powerful grip on the human imagination. The ties that bind us have global connections but…

Einstein-Podolsky-Rosen paradox and quantum steering in pulsed optomechanics

NASA Astrophysics Data System (ADS)

He, Q. Y.; Reid, M. D.

2013-11-01

We describe how to generate an Einstein-Podolsky-Rosen (EPR) paradox between a mesoscopic mechanical oscillator and an optical pulse. We find two types of paradox, defined by whether it is the oscillator or the pulse that shows the effect Schrödinger called “steering”. Only the oscillator paradox addresses the question of mesoscopic local reality for a massive system. In that case, EPR's “elements of reality” are defined for the oscillator, and it is these elements of reality that are falsified (if quantum mechanics is complete). For this sort of paradox, we show that a thermal barrier exists, meaning that a threshold level of pulse-oscillator interaction is required for a given thermal occupation n0 of the oscillator. We find there is no equivalent thermal barrier for the entanglement of the pulse with the oscillator or for the EPR paradox that addresses the local reality of the optical system. Finally, we examine the possibility of an EPR paradox between two entangled oscillators. Our work highlights the asymmetrical effect of thermal noise on quantum nonlocality.

Paradoxical articular manifestations in patients with inflammatory bowel diseases treated with infliximab.

PubMed

Thiebault, Henri; Boyard-Lasselin, Pauline; Guignant, Caroline; Guillaume, Nicolas; Wacrenier, Adrien; Sabbagh, Charles; Rebibo, Lionel; Brazier, Franck; Meynier, Jonathan; Nguyen-Khac, Eric; Dupas, Jean-Louis; Goëb, Vincent; Fumery, Mathurin

2016-08-01

Articular involvement is the most common extraintestinal manifestation associated with inflammatory bowel diseases (IBDs). Manifestations are 'paradoxical' when they occur during treatment, notably with anti-tumor necrosis factor (anti-TNF) drugs, which are expected to prevent or treat them. The aim of this study was to assess the frequency, characteristics, and associated factors of paradoxical articular manifestations in patients with IBD treated with anti-TNF. In this prospective single-center study, an examination by a rheumatologist was systematically offered to all patients with IBD treated with infliximab (IFX) to assess the prevalence of articular manifestations and distinguish between those related to treatment and those associated with intestinal disease. Paradoxical manifestations were defined as the occurrence of articular manifestations (excluding induced lupus and hypersensitivity reactions) during anti-TNF therapy in patients with intestinal remission. Measures of biological inflammatory, immunological markers, HLA-B27 allele, IFX trough levels, and anti-IFX antibody (Ab) were performed for all patients. Between May 2013 and April 2014, 65 patients with Crohn's disease and 15 with patients ulcerative colitis treated with IFX were included. The median duration of anti-TNF therapy was 66 months [quartile (Q)1=23 months-Q3=81 months]. Articular manifestations were observed in 50 (62%) patients treated with IFX. Eleven percent (n=9) were considered to be associated with IBD and 16% (n=13) to be associated with anti-TNF therapy. Among articular manifestations associated with anti-TNF therapy, nine (11%) patients were considered paradoxical, two (2%) as drug-induced lupus, and two (2%) as a hypersensitivity reaction. Among the nine patients with paradoxical manifestations, all had Crohn's disease in clinical remission, three patients presented a spondyloarthropathy, and three developed associated paradoxical psoriasis. No patient discontinued anti-TNF because of the articular manifestations. Methotrexate was effective on articular symptoms in two of the three treated patients with paradoxical manifestations. No clinical or biological factors, including IFX trough levels, were associated with the occurrence of paradoxical manifestations. Paradoxical articular manifestations in IBD patients treated by anti-TNF are common, affecting more than 10% of patients. These events are generally mild and do not need discontinuation of anti-TNF therapy.

Paradoxical self-esteem and selectivity in the processing of social information.

PubMed

Tafarodi, R W

1998-05-01

Paradoxical self-esteem is defined as contrasting levels of self-liking and self-competence. Consideration of the social and motivational implications of this uncommon form of self-esteem suggests that heightened selectivity in the processing of social information may be behind its persistence. Two experiments were conducted to confirm the prediction of heightened selectivity in paradoxicals. As expected, those paradoxically low in self-liking were more negatively biased in their memory for personality feedback (Study 1) and interpretation of valuatively ambiguous phrases (Study 2) than were their counterparts who shared the same low self-liking but were also low in self-competence. Symmetrical with this result, those paradoxically high in self-liking exhibited a heightened positive bias relative to those who were high in both self-liking and self-competence. The findings are discussed in relation to attitudes and motivation.

An analysis of obituaries in staff magazines.

PubMed

Heynderickx, Priscilla C; Dieltjens, Sylvain M

2016-01-01

In the literature, extensive attention is given to the content, structure, and style of obituaries in newspapers. Analyses of the demise of colleagues in internal business communications are however nonexistent. This article discusses a bottom-up analysis of 150 obituaries published in Flemish staff magazines--obituaries that mostly focus on the deceased's career and professional qualities. Following analysis, the data were divided in obituaries that are continuous texts and obituaries with a letter format. The differences between the two types lie at different levels: format, content, structure, and language use. Obituaries with a letter format are characterized and determined by three paradoxes: the sender-receiver paradox, life-death paradox, and happiness-sadness paradox.

Generalized friendship paradox in complex networks: The case of scientific collaboration

NASA Astrophysics Data System (ADS)

Eom, Young-Ho; Jo, Hang-Hyun

2014-04-01

The friendship paradox states that your friends have on average more friends than you have. Does the paradox ``hold'' for other individual characteristics like income or happiness? To address this question, we generalize the friendship paradox for arbitrary node characteristics in complex networks. By analyzing two coauthorship networks of Physical Review journals and Google Scholar profiles, we find that the generalized friendship paradox (GFP) holds at the individual and network levels for various characteristics, including the number of coauthors, the number of citations, and the number of publications. The origin of the GFP is shown to be rooted in positive correlations between degree and characteristics. As a fruitful application of the GFP, we suggest effective and efficient sampling methods for identifying high characteristic nodes in large-scale networks. Our study on the GFP can shed lights on understanding the interplay between network structure and node characteristics in complex networks.

Generalized friendship paradox in complex networks: The case of scientific collaboration

PubMed Central

Eom, Young-Ho; Jo, Hang-Hyun

2014-01-01

The friendship paradox states that your friends have on average more friends than you have. Does the paradox “hold” for other individual characteristics like income or happiness? To address this question, we generalize the friendship paradox for arbitrary node characteristics in complex networks. By analyzing two coauthorship networks of Physical Review journals and Google Scholar profiles, we find that the generalized friendship paradox (GFP) holds at the individual and network levels for various characteristics, including the number of coauthors, the number of citations, and the number of publications. The origin of the GFP is shown to be rooted in positive correlations between degree and characteristics. As a fruitful application of the GFP, we suggest effective and efficient sampling methods for identifying high characteristic nodes in large-scale networks. Our study on the GFP can shed lights on understanding the interplay between network structure and node characteristics in complex networks. PMID:24714092

The paradox of enrichment in phytoplankton by induced competitive interactions

PubMed Central

Tubay, Jerrold M.; Ito, Hiromu; Uehara, Takashi; Kakishima, Satoshi; Morita, Satoru; Togashi, Tatsuya; Tainaka, Kei-ichi; Niraula, Mohan P.; Casareto, Beatriz E.; Suzuki, Yoshimi; Yoshimura, Jin

2013-01-01

The biodiversity loss of phytoplankton with eutrophication has been reported in many aquatic ecosystems, e.g., water pollution and red tides. This phenomenon seems similar, but different from the paradox of enrichment via trophic interactions, e.g., predator-prey systems. We here propose the paradox of enrichment by induced competitive interactions using multiple contact process (a lattice Lotka-Volterra competition model). Simulation results demonstrate how eutrophication invokes more competitions in a competitive ecosystem resulting in the loss of phytoplankton diversity in ecological time. The paradox is enhanced under local interactions, indicating that the limited dispersal of phytoplankton reduces interspecific competition greatly. Thus, the paradox of enrichment appears when eutrophication destroys an ecosystem either by elevated interspecific competition within a trophic level and/or destabilization by trophic interactions. Unless eutrophication due to human activities is ceased, the world's aquatic ecosystems will be at risk. PMID:24089056

Intimate partner violence against women and the Nordic paradox.

PubMed

Gracia, Enrique; Merlo, Juan

2016-05-01

Nordic countries are the most gender equal countries in the world, but at the same time they have disproportionally high prevalence rates of intimate partner violence (IPV) against women. High prevalence of IPV against women, and high levels of gender equality would appear contradictory, but these apparently opposite statements appear to be true in Nordic countries, producing what could be called the 'Nordic paradox'. Despite this paradox being one of the most puzzling issues in the field, this is a research question rarely asked, and one that remains unanswered. This paper explores a number of theoretical and methodological issues that may help to understand this paradox. Efforts to understand the Nordic paradox may provide an avenue to guide new research on IPV and to respond to this major public health problem in a more effective way. Copyright © 2016 Elsevier Ltd. All rights reserved.

John Stuart Mill's Concepts of Quality and Pedagogical Norms.

ERIC Educational Resources Information Center

Kim, Ki Su

1986-01-01

Considers the paradoxical relationship between two pervasive educational goals--quality and equality. Sees this paradox embedded in John Stuart Mill's writings on education, which attempted to reconcile the utilitarian pleasure principle (which emphasizes quantitative measures), with a traditional differentiation among levels and kinds of desires…

DNA Binding of Centromere Protein C (CENPC) Is Stabilized by Single-Stranded RNA

PubMed Central

Du, Yaqing; Topp, Christopher N.; Dawe, R. Kelly

2010-01-01

Centromeres are the attachment points between the genome and the cytoskeleton: centromeres bind to kinetochores, which in turn bind to spindles and move chromosomes. Paradoxically, the DNA sequence of centromeres has little or no role in perpetuating kinetochores. As such they are striking examples of genetic information being transmitted in a manner that is independent of DNA sequence (epigenetically). It has been found that RNA transcribed from centromeres remains bound within the kinetochore region, and this local population of RNA is thought to be part of the epigenetic marking system. Here we carried out a genetic and biochemical study of maize CENPC, a key inner kinetochore protein. We show that DNA binding is conferred by a localized region 122 amino acids long, and that the DNA-binding reaction is exquisitely sensitive to single-stranded RNA. Long, single-stranded nucleic acids strongly promote the binding of CENPC to DNA, and the types of RNAs that stabilize DNA binding match in size and character the RNAs present on kinetochores in vivo. Removal or replacement of the binding module with HIV integrase binding domain causes a partial delocalization of CENPC in vivo. The data suggest that centromeric RNA helps to recruit CENPC to the inner kinetochore by altering its DNA binding characteristics. PMID:20140237

Middle ground approach to paradox: Within- and between-culture examination of the creative benefits of paradoxical frames.

PubMed

Leung, Angela K-Y; Liou, Shyhnan; Miron-Spektor, Ella; Koh, Brandon; Chan, David; Eisenberg, Roni; Schneider, Iris

2018-03-01

Thriving in increasingly complex and ambiguous environments requires creativity and the capability to reconcile conflicting demands. Recent evidence with Western samples has suggested that paradoxical frames, or mental templates that encourage individuals to recognize and embrace contradictions, could produce creative benefits. We extended the timely, but understudied, topic by studying the nuances of for whom and why creative advantages of paradoxical frames emerge. We suggest that people endorsing a middle ground approach are less likely to scrutinize conflict and reconcile with integrative solutions, thus receiving less creative benefits of paradoxical frames. Five studies that examined individual and cultural differences in middle ground endorsement support our theory. Study 1 found that paradoxical frames increased creativity, but failed to replicate that experienced conflict mediated the relationship in a Taiwanese sample. In both within- and between-culture analysis, we showed that the creative advantages of thinking paradoxically and experiencing conflict emerged among individuals who endorse lower (vs. higher) levels of middle ground (Study 2) and among Israelis whose culture predominantly endorses middle ground strategy less, but not among Singaporeans whose culture predominantly endorses middle ground more (Study 3). Study 4 further demonstrated the causal role of middle ground in the paradox-conflict-creativity link. To answer "why," Study 5 situationally induced integrative complex thinking that sets distinctions and forms syntheses among contradictory elements, and found that low endorsers of middle ground performed more creatively when they engaged integrative complex thinking to cope with paradoxes. This program of studies offers important insights on harnessing paradoxical experiences to catalyze creativity. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The quantum measurement problem.

PubMed

Leggett, A J

2005-02-11

Despite the spectacular success of quantum mechanics (QM) over the last 80 years in explaining phenomena observed at the atomic and subatomic level, the conceptual status of the theory is still a topic of lively controversy. Most of the discussion centers around two famous paradoxes (or, as some would have it, pseudoparadoxes) associated, respectively, with the names of Einstein, Podolsky, and Rosen (EPR) and with Schrodinger's cat. In this Viewpoint, I will concentrate on the paradox of Schrodinger's cat or, as it is often known (to my mind somewhat misleadingly), the quantum measurement paradox.

How Much Does a Half-Kilogram of Water "Weigh"?

NASA Astrophysics Data System (ADS)

Koumaras, Panagiotis; Pierratos, Theodoros

2015-03-01

Many educators have utilized the phenomenon of the so-called "hydrostatic paradox" to actively engage students in classroom instructional activities related to hydrostatic equilibrium.1 Various approaches requiring different levels of mathematical knowledge have been proposed in the literature to provide students clear explanations of this paradox.2 However, these attempts take for granted that students have already been taught and have internalized the concepts of force and pressure. The hydrostatic paradox is then usually introduced as an application problem for the evaluation of the knowledge acquired.

The Resolution of Some Paradoxes Related to Reliability and Validity

ERIC Educational Resources Information Center

Li, Heng

2003-01-01

Attention is brought to the existence of incongruity in the definition of reliability in the literature, and some unnecessary controversies and confusions which result. A conventionalization of the meaning of reliability at a conceptual, model-free level is proposed. Through the exploration of two paradoxes, this article attempts to address some…

Spin entanglement, decoherence and Bohm's EPR paradox.

PubMed

Cavalcanti, E G; Drummond, P D; Bachor, H A; Reid, M D

2009-10-12

We obtain criteria for entanglement and the EPR paradox for spin-entangled particles and analyse the effects of decoherence caused by absorption and state purity errors. For a two qubit photonic state, entanglement can occur for all transmission efficiencies. In this case, the state preparation purity must be above a threshold value. However, Bohm's spin EPR paradox can be achieved only above a critical level of loss. We calculate a required efficiency of 58%, which appears achievable with current quantum optical technologies. For a macroscopic number of particles prepared in a correlated state, spin entanglement and the EPR paradox can be demonstrated using our criteria for efficiencies eta > 1/3 and eta > 2/3 respectively. This indicates a surprising insensitivity to loss decoherence, in a macroscopic system of ultra-cold atoms or photons.

Design principles of paradoxical signaling in the immune system

NASA Astrophysics Data System (ADS)

Hart, Yuval

A widespread feature of cell-cell signaling systems is paradoxical pleiotropy: the same secreted signaling molecule can induce opposite effects in the responding cells. For example, the cytokine IL-2 can promote proliferation and death of T-cells. The role of such paradoxical signaling remains unclear. We suggest that this mechanism provides homeostatic concentration of cells, independent of initial conditions. The crux of the paradoxical mechanism is the combination of a positive and a negative feedback loops creating two stable states - an OFF state and an ON state. Experimentally, we found that CD4 + cells grown in culture with a 30-fold difference in initial concentrations reached a homeostatic concentration nearly independent of initial cell levels (ON-state). Below an initial threshold, cell density decayed to extinction (OFF-state). Mathematical modeling explained the observed cell and cytokine dynamics and predicted conditions that shifted cell fate from homeostasis to the OFF-state. We suggest that paradoxical signaling provides cell circuits with specific dynamical features that are robust to environmental perturbations.

Conclusion: The Era of Mass Early Career Academics and Aging Faculty--Africa's Paradox

ERIC Educational Resources Information Center

Teferra, Damtew

2016-01-01

African higher education has witnessed phenomenal enrollment growth in the last decade--and this trend is expected to continue well into the future owing to the continent's youth bulge. In this "massifying" system, the academic profession faces a paradox: as the academic profession at the senior level is aging it is also concurrently…

Doing Well vs. Feeling Well: Understanding Family Dynamics and the Psychological Adjustment of Chinese Immigrant Adolescents

ERIC Educational Resources Information Center

Qin, Desiree Baolian

2008-01-01

Despite their average high levels of educational achievement, Asian American students often report poor psychological and social adjustment, suggesting an achievement/adjustment paradox. Yet, the reasons for this paradox remain unclear. Drawing on 5-year longitudinal qualitative interview data, this paper compares the family dynamics of two groups…

Social Capital and Human Mortality: Explaining the Rural Paradox with County-Level Mortality Data

PubMed Central

Jensen, Leif; Haran, Murali

2014-01-01

The “rural paradox” refers to standardized mortality rates in rural areas that are unexpectedly low in view of well-known economic and infrastructural disadvantages there. We explore this paradox by incorporating social capital, a promising explanatory factor that has seldom been incorporated into residential mortality research. We do so while being attentive to spatial dependence, a statistical problem often ignored in mortality research. Analyzing data for counties in the contiguous United States, we find that: (1) the rural paradox is confirmed with both metro/non-metro and rural-urban continuum codes, (2) social capital significantly reduces the impacts of residence on mortality after controlling for race/ethnicity and socioeconomic covariates, (3) this attenuation is greater when a spatial perspective is imposed on the analysis, (4) social capital is negatively associated with mortality at the county level, and (5) spatial dependence is strongly in evidence. A spatial approach is necessary in county-level analyses such as ours to yield unbiased estimates and optimal model fit. PMID:25392565

Paradoxical Pain Perception in Posttraumatic Stress Disorder: The Unique Role of Anxiety and Dissociation.

PubMed

Defrin, Ruth; Schreiber, Shaul; Ginzburg, Karni

2015-10-01

Posttraumatic stress disorder (PTSD) and chronic pain often co-occur and exacerbate each other. Elucidating the mechanism of this co-occurrence therefore has clinical importance. Previously, patients with PTSD with chronic pain were found to demonstrate a unique paradoxical pain profile: hyperresponsiveness together with hyposensitivity to pain. Our aim was to examine whether 2 seemingly paradoxical facets of PTSD (anxiety and dissociation) underlie this paradoxical profile. Patients with PTSD (n = 32) and healthy control individuals (n = 43) underwent psychophysical testing and completed questionnaires. Patients with PTSD had higher pain thresholds and higher pain ratings to suprathreshold stimuli than control individuals. Pain thresholds were positively associated with dissociation levels and negatively associated with anxiety sensitivity levels. Experimental pain ratings were positively associated with anxiety sensitivity and negatively related to dissociation levels. Chronic pain intensity was associated with anxiety, anxiety sensitivity, and pain catastrophizing. It appears that reduced conscious attention toward incoming stimuli, resulting from dissociation, causes delayed response in pain threshold measurement, whereas biases toward threatening stimuli and decreased inhibition, possibly caused by increased anxiety, are responsible for the intensification of experimental and chronic pain. The paradoxical facets of PTSD and their particular influences over pain perception seem to reinforce the coexistence of PTSD and chronic pain, and should be considered when treating traumatized individuals. This article provides new information regarding the underlying mechanism of the coexistence of PTSD and chronic pain. This knowledge could help to provide better management of PTSD and chronic pain among individuals in the aftermath of trauma. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Contrasting acute graft-versus-host disease effects of Tim-3/galectin-9 pathway blockade dependent upon the presence of donor regulatory T cells

PubMed Central

Veenstra, Rachelle G.; Taylor, Patricia A.; Zhou, Qing; Panoskaltsis-Mortari, Angela; Hirashima, Mitsuomi; Flynn, Ryan; Liu, Derek; Anderson, Ana C.; Strom, Terry B.; Kuchroo, Vijay K.

2012-01-01

T-cell immunoglobulin mucin-3 (Tim-3) is expressed on pathogenic T cells, and its ligand galectin-9 (gal-9) is up-regulated in inflamed tissues. When Tim-3+ T cells encounter high gal-9 levels, they are deleted. Tim-3 is up-regulated on activated T cells during GVHD. Inhibition of Tim-3/gal-9 binding by infusion of a Tim-3-Ig fusion protein or Tim-3−/− donor T cells increased T-cell proliferation and GVHD lethality. When the Tim-3/gal-9 pathway engagement was augmented using gal-9 transgenic recipients, GVHD lethality was slowed. Together, these data indicate a potential for modulating this pathway to reduce disease by increasing Tim-3 or gal-9 engagement. Paradoxically, when Tim-3/gal-9 was inhibited in the absence of donor T-regulatory cells (Tregs), GVHD was inhibited. GVHD reduction was associated with decreased colonic inflammatory cytokines as well as epithelial barrier destruction. CD25-depleted Tim-3−/− donor T cells underwent increased activation-induced cell death because of increased IFN-γ production. To our knowledge, these studies are the first to show that although the absence of Tim-3/gal-9 pathway interactions augments systemic GVHD, concurrent donor Treg depletion paradoxically and surprisingly inhibits GVHD. Thus, although donor Tregs typically inhibit GVHD, under some conditions, such Tregs actually may contribute to GVHD by reducing activation-induced T-cell death. PMID:22677125

Inductive reasoning and judgment interference: experiments on Simpson's paradox.

PubMed

Fiedler, Klaus; Walther, Eva; Freytag, Peter; Nickel, Stefanie

2003-01-01

In a series of experiments on inductive reasoning, participants assessed the relationship between gender, success, and a covariate in a situation akin to Simpson's paradox: Although women were less successful then men according to overall statistics, they actually fared better then men at either of two universities. Understanding trivariate relationships of this kind requires cognitive routines similar to analysis of covariance. Across the first five experiments, however, participants generalized the disadvantage of women at the aggregate level to judgments referring to the different levels of the covariate, even when motivation was high and appropriate mental models were activated. The remaining three experiments demonstrated that Simpson's paradox could be mastered when the salience of the covariate was increased and when the salience of gender was decreased by the inclusion of temporal cues that disambiguate the causal status of the covariate. Copyright 2003 Society for Personality and Social Psychology, Inc.

The integration paradox: level of education and immigrants' attitudes towards natives and the host society.

PubMed

de Vroome, Thomas; Martinovic, Borja; Verkuyten, Maykel

2014-04-01

The so-called integration paradox refers to the phenomenon of the economically more integrated and highly educated immigrants turning away from the host society, instead of becoming more oriented toward it. The present study examined this paradox in the Netherlands among a large sample (N = 3,981) of immigrants, including 2 generations and 4 ethnic groups. The assumed negative relationship between level of education and attitudes toward the host society and the native population was expected to be mediated by two indicators of perceived acceptance by the native majority: discrimination and subgroup respect. Results show that higher educated immigrants perceive more discrimination and less respect for minorities, and these perceptions, in turn, relate to less positive evaluations of the native majority and the host society. This pattern of associations is quite similar for the 2 generations and for the 4 migrant groups.

Making Games Not Work: Paradoxes Embedded in Game-Based Training and Concepts for Overcoming Them

NASA Technical Reports Server (NTRS)

Jones, Phillip N.; Cuper, Taryn

2010-01-01

An interest in game-based training solutions is natural. All one has to do is watch someone fully engaged in a modern game to see the potential of harnessing that attention for training. However, the reality of game-based training has not fully satisfied these expectations. This paper explains two paradoxes that must be overcome for games to support training. These paradoxes are a result of the realities of the basic human condition clashing with the requirements of learning theory. 80th paradoxes arise from the concept of "engagement" that is central to games. The first comes from a more robust definition of engagement, which is the condition of Flow or Optimal Experience. Flow is the state game developers want to see in users. One aspect of Flow is loss of sense of self as the individual becomes immersed in the experience. The paradox arises because this loss of self directly contradicts the learning requirement of self-reflection. The second paradox comes from theories of play, which state in part that play requires a level of individual freedom. The contradiction arises when game-based play must be harnessed to an organizational training program or regimen. The paper will discuss these paradoxes in the context of an effort to design a game-based training modality to train combat medics and will close with a review of compensating strategies identified by the designers. The paper will provide information important to anyone interested in conceptualizing and designing game-based training.

ATRX binds to atypical chromatin domains at the 3′ exons of zinc finger genes to preserve H3K9me3 enrichment

PubMed Central

Chowdhury, Asif H.; Hasson, Dan; Dyer, Michael A.

2016-01-01

ABSTRACT ATRX is a SWI/SNF chromatin remodeler proposed to govern genomic stability through the regulation of repetitive sequences, such as rDNA, retrotransposons, and pericentromeric and telomeric repeats. However, few direct ATRX target genes have been identified and high-throughput genomic approaches are currently lacking for ATRX. Here we present a comprehensive ChIP-sequencing study of ATRX in multiple human cell lines, in which we identify the 3′ exons of zinc finger genes (ZNFs) as a new class of ATRX targets. These 3′ exonic regions encode the zinc finger motifs, which can range from 1–40 copies per ZNF gene and share large stretches of sequence similarity. These regions often contain an atypical chromatin signature: they are transcriptionally active, contain high levels of H3K36me3, and are paradoxically enriched in H3K9me3. We find that these ZNF 3′ exons are co-occupied by SETDB1, TRIM28, and ZNF274, which form a complex with ATRX. CRISPR/Cas9-mediated loss-of-function studies demonstrate (i) a reduction of H3K9me3 at the ZNF 3′ exons in the absence of ATRX and ZNF274 and, (ii) H3K9me3 levels at atypical chromatin regions are particularly sensitive to ATRX loss compared to other H3K9me3-occupied regions. As a consequence of ATRX or ZNF274 depletion, cells with reduced levels of H3K9me3 show increased levels of DNA damage, suggesting that ATRX binds to the 3′ exons of ZNFs to maintain their genomic stability through preservation of H3K9me3. PMID:27029610

Different Roles for Contracture and Calpain in Calcium Paradox-Induced Heart Injury

PubMed Central

Zhang, Jian-Ying; Bi, Sheng-Hui; Xu, Ming; Jin, Zhen-Xiao; Yang, Yang; Jiang, Xiao-Fan; Zhou, Jing-Jun

2012-01-01

The Ca2+ paradox represents a good model to study Ca2+ overload injury in ischemic heart diseases. We and others have demonstrated that contracture and calpain are involved in the Ca2+ paradox-induced injury. This study aimed to elucidate their roles in this model. The Ca2+ paradox was elicited by perfusing isolated rat hearts with Ca2+-free KH media for 3 min or 5 min followed by 30 min of Ca2+ repletion. The LVDP was measured to reflect contractile function, and the LVEDP was measured to indicate contracture. TTC staining and the quantification of LDH release were used to define cell death. Calpain activity and troponin I release were measured after Ca2+ repletion. Ca2+ repletion of the once 3-min Ca2+ depleted hearts resulted in almost no viable tissues and the disappearance of contractile function. Compared to the effects of the calpain inhibitor MDL28170, KB-R7943, an inhibitor of the Na+/Ca2+ exchanger, reduced the LVEDP level to a greater extent, which was well correlated with improved contractile function recovery and tissue survival. The depletion of Ca2+ for 5 min had the same effects on injury as the 3-min Ca2+ depletion, except that the LVEDP in the 5-min Ca2+ depletion group was lower than the level in the 3-min Ca2+ depletion group. KB-R7943 failed to reduce the level of LVEDP, with no improvement in the LVDP recovery in the hearts subjected to the 5-min Ca2+ depletion treatment; however, KB-R7943 preserved its protective effects in surviving tissue. Both KB-R7943 and MDL28170 attenuated the Ca2+ repletion-induced increase in calpain activity in 3 min or 5 min Ca2+ depleted hearts. However, only KB-R7943 reduced the release of troponin I from the Ca2+ paradoxic heart. These results provide evidence suggesting that contracture is the main cause for contractile dysfunction, while activation of calpain mediates cell death in the Ca2+ paradox. PMID:23284963

Substitutions in PBP2b from β-Lactam-resistant Streptococcus pneumoniae Have Different Effects on Enzymatic Activity and Drug Reactivity*

PubMed Central

Calvez, Philippe; Breukink, Eefjan; Roper, David I.; Dib, Mélanie; Contreras-Martel, Carlos; Zapun, André

2017-01-01

Pneumococcus resists β-lactams by expressing variants of its target enzymes, the penicillin-binding proteins (PBPs), with many amino acid substitutions. Up to 10% of the sequence can be modified. These altered PBPs have a much reduced reactivity with the drugs but retain their physiological activity of cross-linking the peptidoglycan, the major constituent of the bacterial cell wall. However, because β-lactams are chemical and structural mimics of the natural substrate, resistance mediated by altered PBPs raises the following paradox: how PBPs that react poorly with the drugs maintain a sufficient level of activity with the physiological substrate. This question is addressed for the first time in this study, which compares the peptidoglycan cross-linking activity of PBP2b from susceptible and resistant strains with their inhibition by different β-lactams. Unexpectedly, the enzymatic activity of the variants did not correlate with their antibiotic reactivity. This finding indicates that some of the numerous amino acid substitutions were selected to restore a viable level of enzymatic activity by a compensatory molecular mechanism. PMID:28062575

Perfectionism and Anxiety: A Paradox in Intellectual Giftedness?

PubMed Central

Guignard, Jacques-Henri; Jacquet, Anne-Yvonne; Lubart, Todd I.

2012-01-01

Numerous authors reported a prevalence of perfectionism in gifted populations. In addition, an unhealthy form of perfectionism that leads to anxiety disorder has been described. Using self-report measures (CAPS and R-CMAS) with 132 children, we hypothesized that intellectually gifted children express a higher level of perfectionism and anxiety. Our results pointed out a paradox: the gifted group obtained a higher self-oriented perfectionism score than the control group in 6th grade, but present the same level of anxiety. In contrast, the gifted group showed the same level of perfectionism than non-gifted 5th graders, but reported a higher anxiety level. Thus, the interplay between perfectionism and anxiety appears to be more complex than a simple linear relationship in giftedness. PMID:22859964

Antibodies with 'Original Antigenic Sin' Properties Are Valuable Components of Secondary Immune Responses to Influenza Viruses.

PubMed

Linderman, Susanne L; Hensley, Scott E

2016-08-01

Human antibodies (Abs) elicited by influenza viruses often bind with a high affinity to past influenza virus strains, but paradoxically, do not bind to the viral strain actually eliciting the response. This phenomena is called 'original antigenic sin' (OAS) since this can occur at the expense of generating new de novo Abs. Here, we characterized the specificity and functionality of Abs elicited in mice that were sequentially exposed to two antigenically distinct H1N1 influenza virus strains. Many Abs elicited under these conditions had an OAS phenotype, in that they bound strongly to the viral strain used for the first exposure and very weakly to the viral strain used for the second exposure. We found that OAS and non-OAS Abs target the same general region of the influenza hemagglutinin protein and that B cells expressing these two types of Abs can be clonally-related. Surprisingly, although OAS Abs bound with very low affinities, some were able to effectively protect against an antigenically drifted viral strain following passive transfer in vivo. Taken together, our data indicate that OAS Abs share some level of cross-reactivity between priming and recall viral strains and that B cells producing these Abs can be protective when recalled into secondary immune responses.

Dying or living?: The double bind.

PubMed

Longhofer, J

1980-06-01

Describing the behaviors of terminally ill patients, their families and those charged with their care has received considerable attention during the past decade. This study of comprehensive cancer treatment and research facility indicates that the prevailing theory is limited to explanation at the intra-psychic level. In her work with hundreds of terminal cases, Dr. Elizabeth Kubler-Ross found that patients typically progress through five stages: 1) denial, 2) anger, 3) bargaining, 4) depression, and 5) acceptance. She concludes that the majority of her patients die in a stage of acceptance--a state of equanimity. Recently, scholars have claimed that this five stage scheme has limited applicability and may in fact contribute to the formalization of a dying person's behavior. This preliminary report proposes that the stage theory, if it has any descriptive validity, becomes meaningful only when used to describe behaviors occurring among patients, families, and medical practitioners. A plausible explanation of these behaviors is accomplished by examination of communication patterns containing the structure of paradox or double bind. Patients are forced to perceive realities about their physical conditions not as they appear to them, but as they are defined by those in their environment. This paper explores these communication patterns in relation to the structure of social relationships and the specific contents of messages being transmitted and received.

The calcium paradox phenomenon: a flow rate and volume response study of calcium-free perfusion.

PubMed

Oksendal, A N; Jynge, P; Sellevold, O F; Rotevatn, S; Saetersdal, T

1985-10-01

A dose-response study concerning the importance of the flow rate (0.5 to 12 ml/min) and volume (2.5 to 60 ml) of calcium-free coronary perfusion (duration 5 min) in the induction of a calcium paradox on reperfusion (duration 15 min) with calcium-containing medium has been performed in the isolated rat heart (37 degrees C). On the basis of enzymatic, physiological, and metabolic assessments three different levels of tissue injury were identified: a minimal paradox at 1.0 ml/min or 5 ml, a subtotal paradox at 2 ml/min or 10 ml and a total paradox at 9 ml/min or 45 ml. Ultrastructural examination revealed that cellular injury following calcium repletion was always severe, and that an increase in the flow rate and volume of calcium-free perfusion increased the number of severely injured cells. During calcium-free perfusion the external lamina largely remained intact over the surface coat of the sarcolemma, but variable degrees of separation of intercalated discs were observed. It is concluded that the calcium paradox model of myocardial injury presents a rather sharp threshold related to the flow rate or volume of calcium-free coronary perfusion and that on trespassing this threshold there is a narrow zone characterized by a decreasing number of viable cells. Furthermore, the study indicates that a separation of the external lamina from the surface coat of the sarcolemma is not a prerequisite for the induction of a calcium paradox, and that cell injury may occur in the presence of intact intercalated discs.

Vitamin paradox in obesity: Deficiency or excess?

PubMed

Zhou, Shi-Sheng; Li, Da; Chen, Na-Na; Zhou, Yiming

2015-08-25

Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis.

Vitamin paradox in obesity: Deficiency or excess?

PubMed Central

Zhou, Shi-Sheng; Li, Da; Chen, Na-Na; Zhou, Yiming

2015-01-01

Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis. PMID:26322161

[Paradoxical effect of methylphenidate in the treatment of a patient with severe traumatic brain injury].

PubMed

Grønborg, Pia; Liljegren, Jeanette; Jansen, Jette

2009-06-22

Methylphenidate is a central nervous system (CNS)-stimulating agent. During recent years methylphenidate has been shown to increase arousal in patients with traumatic brain injury. We describe a patient with a severe traumatic injury in whom arousal was increased when methylphenidate was given, and the level of arousal decreased when the amount was diminished after some months. Due to possible side effects, methylphenidate treatment was reduced over several weeks 2 years after the trauma. Surprisingly, the cognitive level was then dramatically improved. To our knowledge, such paradoxical effect of methylphenidate has not previously been described.

[Effect of 2,3-butanedione monoxime on calcium paradox-induced heart injury in rats].

PubMed

Kong, Ling-Heng; Gu, Xiao-Ming; Su, Xing-Li; Sun, Na; Wei, Ming; Zhu, Juan-Xia; Chang, Pan; Zhou, Jing-Jun

2016-05-01

To investigate the Effect of 2,3-butanedione monoxime (BDM) on calcium paradox-induced heart injury and its underlying mechanisms. Thirty-two adult male SD rats were randomized into 4 groups, namely the control group, BDM treatment control group, calcium paradox group, and BDM treatment group. Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion and the left ventricular pressure (LVP) and left ventricular end-diastolic pressure (LVEDP) were monitored. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Lactate dehydrogenase (LDH) content in the coronary flow was determined. Triphenyltetrazolium chloride staining was used to measure the infarct size, and myocardial cell apoptosis was tested with TUNEL method. Western blotting was used to determine the expression of cleaved caspase-3 and cytochrome c. Compared with the control group, BDM at 20 mmol/L had no effect on cardiac performance, cell death, apoptotic index or the content of LDH, cleaved caspase-3 and cytochrome c at the end of perfusion under control conditions (P>0.05). Calcium paradox treatment significantly decreased the cardiac function and the level of LVDP and induced a larger infarct size (P<0.01), an increased myocardial apoptosis index (P<0.01), and up-regulated expressions of cleaved caspase-3 and cytochrome c (P<0.01). BDM (20 mmol/L) significantly attenuated these effects induced by calcium paradox, and markedly down-regulated the levels of LVEDP and LDH (P<0.01), lowered myocardial apoptosis index, decreased the content of cleaved caspase-3 and cytochrome c (P<0.01), increased LVDP, and reduced the infarct size (P<0.01). BDM suppresses cell apoptosis and contracture and improves heart function and cell survival in rat hearts exposed to calcium paradox, suggesting the value of BDM as an potential drug for myocardial ischemia reperfusion injur.

Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) in HIV Patients with Culture Confirmed Pulmonary Tuberculosis in India and the Potential Role of IL-6 in Prediction

PubMed Central

Porter, Brian O.; Chandrasekhar, Chockalingam; Venkatesan, Perumal; Menon, Pradeep A.; Subramanian, Sudha; Anbalagan, Selvaraj; Bhavani, Kannabiran P.; Sekar, Sathiyavelu; Padmapriyadarshini, Chandrasekaran; Kumar, Satagopan; Ravichandran, Narayanan; Raja, Krishnaraj; Bhanu, Kesavamurthy; Mahilmaran, Ayyamperumal; Sekar, Lakshmanan; Sher, Alan; Sereti, Irini; Swaminathan, Soumya

2013-01-01

Background The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. Methods HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. Results Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14–47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7–16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9–23). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. Conclusion Paradoxical TB–IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions. PMID:23691062

Paradoxical Regulation of Human FGF21 by Both Fasting and Feeding Signals: Is FGF21 a Nutritional Adaptation Factor?

PubMed Central

Uebanso, Takashi; Taketani, Yutaka; Yamamoto, Hironori; Amo, Kikuko; Ominami, Hirokazu; Arai, Hidekazu; Takei, Yuichiro; Masuda, Masashi; Tanimura, Ayako; Harada, Nagakatsu; Yamanaka-Okumura, Hisami; Takeda, Eiji

2011-01-01

Fibroblast growth factor 21 (FGF21) has recently emerged as a metabolic hormone involved in regulating glucose and lipid metabolism in mouse, but the regulatory mechanisms and actions of FGF21 in humans remain unclear. Here we have investigated the regulatory mechanisms of the human FGF21 gene at the transcriptional level. A deletion study of the human FGF21 promoter (−1672 to +230 bp) revealed two fasting signals, including peroxisome proliferator-activated receptor α (PPARα) and glucagon signals, that independently induced human FGF21 gene transcription in mouse primary hepatocytes. In addition, two feeding signals, glucose and xylitol, also dose-dependently induced human FGF21 gene transcription and mRNA expression in both human HepG2 cells and mouse primary hepatocytes. FGF21 protein expression and secretion were also induced by high glucose stimulation. The human FGF21 promoter (−1672 to +230 bp) was found to have a carbohydrate-responsive element at −380 to −366 bp, which is distinct from the PPAR response element (PPRE). Knock-down of the carbohydrate response element binding protein by RNAi diminished glucose-induced human FGF21 transcription. Moreover, we found that a region from −555 to −443 bp of the human FGF21 promoter region exerts an important role in the activation of basic transcription. In conclusion, human FGF21 gene expression is paradoxically and independently regulated by both fasting and feeding signals. These regulatory mechanisms suggest that human FGF21 is increased with nutritional crisis, including starvation and overfeeding. PMID:21829679

A Canadian paradox: Tommy Douglas and eugenics.

PubMed

Shevell, Michael

2012-01-01

Tommy Douglas is an icon of Canadian 20th Century political history and is considered by many as the "Father" of Medicare, a key component of our national identity. Throughout his career, he was associated at both the provincial and federal levels with progressive causes concerning disadvantaged populations. In his sociology Master's thesis written in the early 1930's, Douglas endorsed eugenic oriented solutions such as segregation and sterilization to address what was perceived to be an endemic and biologically determined problem. At first glance, this endorsement of eugenics appears to be paradoxical, but careful analysis revealed that this paradox has multiple roots in religion, political belief, historical exposure and our own desire to view our collective history in a favourable light.

Energetic studies on DNA-peptide interaction in relation to the enthalpy-entropy compensation paradox.

PubMed

Yang, Robin C K; Huang, Jonathan T B; Chien, Shih-Chuan; Huang, Roy; Jeng, Kee-Ching G; Chen, Yen-Chung; Liao, Mokai; Wu, Jia-Rong; Hung, Wei-Kang; Hung, Chia-Chun; Chen, Yu-Ling; Waring, Michael J; Sheh, Leung

2013-01-07

This study aims to interpret the energetic basis of complex DNA-peptide interactions according to a novel allosteric interaction network approach. In common with other designed peptides, five new conjugates incorporating the XPRK or XHypRK motif (Hyp = hydroxyproline) attached to a N-methylpyrrole (Py) tract with a basic tail have been found to display cooperative binding to DNA involving multiple monodentate as well as interstrand bidentate interactions. Using quantitative DNase I footprinting it appears that allosteric communication via cooperative binding to multiple sites on complementary DNA strands corresponds to two different types of DNA-peptide interaction network. Temperature variation experiments using a dodecapeptide RY-12 show that lower temperature (25 °C) favor a circuit type of allosteric interaction network, whereas higher temperatures (31 and 37 °C) afford only a partial-circuit type of network. Circular dichroism studies show that our five peptides induce significant local conformational changes in DNA via the minor groove, with apparently dimeric binding stoichiometry. Isothermal titration calorimetry reveals that these peptides, together with another seven for comparison, are strongly exothermic upon binding to a model 13-mer DNA duplex, characterized by ΔH ranging from -14.7 to -74.4 kcal mol(-1), and also high TΔS ranging from -6.5 to -65.9 kcal mol(-1). Multiple monodentate and bidentate interactions, as well as ionic forces that mediate positive cooperativity in sequence recognition, are consistent with a dramatic decrease in entropy and a 'tightening' effect of DNA conformation. Distinctive enthalpy-entropy compensation (EEC) relationships are demonstrated for the interaction of all twelve designed peptides with DNA, affording a straight line of slope close to unity when ΔH is plotted versus TΔS, with a y-axis intercept (average ΔG) corresponding to -8.5 kcal mol(-1), while the observed ΔG ranges from -8.2 to -9.1 kcal mol(-1) for the peptides. The EEC seen with peptide RY-12 binding to the model duplex persists throughout various incubation temperatures. The net compensation of energy between the favorable negative ΔH and unfavorable negative ΔS components thus constrains the value of net binding free energy ΔG within a remarkably constant range, as is clearly visible in a 3-dimensional energetic plot. We conclude that the preservation of a rather narrowly-defined ΔG value is central to the EEC in DNA-peptide interactions, illuminating the universal EEC paradox commonly found in diverse biochemical reactions.

Modeling total cholesterol as predictor of mortality: the low-cholesterol paradox.

PubMed

Wesley, David; Cox, Hugh F

2011-01-01

Elevated total cholesterol is well-established as a risk factor for coronary artery disease and cardiovascular mortality. However, less attention is paid to the association between low cholesterol levels and mortality--the low cholesterol paradox. In this paper, restricted cubic splines (RCS) and complex survey methodology are used to show the low-cholesterol paradox is present in the laboratory, examination, and mortality follow-up data from the Third National Health and Nutrition Examination Survey (NHANES III). A series of Cox proportional hazard models, demonstrate that RCS are necessary to incorporate desired covariates while avoiding the use of categorical variables. Valid concerns regarding the accuracy of such predictive models are discussed. The one certain conclusion is that low cholesterol levels are markers for excess mortality, just as are high levels. Restricted cubic splines provide the necessary flexibility to demonstrate the U-shaped relationship between cholesterol and mortality without resorting to binning results. Cox PH models perform well at identifying associations between risk factors and outcomes of interest such as mortality. However, the predictions from such a model may not be as accurate as common statistics suggest and predictive models should be used with caution.

Paradox of enrichment: A fractional differential approach with memory

NASA Astrophysics Data System (ADS)

Rana, Sourav; Bhattacharya, Sabyasachi; Pal, Joydeep; N'Guérékata, Gaston M.; Chattopadhyay, Joydev

2013-09-01

The paradox of enrichment (PoE) proposed by Rosenzweig [M. Rosenzweig, The paradox of enrichment, Science 171 (1971) 385-387] is still a fundamental problem in ecology. Most of the solutions have been proposed at an individual species level of organization and solutions at community level are lacking. Knowledge of how learning and memory modify behavioral responses to species is a key factor in making a crucial link between species and community levels. PoE resolution via these two organizational levels can be interpreted as a microscopic- and macroscopic-level solution. Fractional derivatives provide an excellent tool for describing this memory and the hereditary properties of various materials and processes. The derivatives can be physically interpreted via two time scales that are considered simultaneously: the ideal, equably flowing homogeneous local time, and the cosmic (inhomogeneous) non-local time. Several mechanisms and theories have been proposed to resolve the PoE problem, but a universally accepted theory is still lacking because most studies have focused on local effects and ignored non-local effects, which capture memory. Here we formulate the fractional counterpart of the Rosenzweig model and analyze the stability behavior of a system. We conclude that there is a threshold for the memory effect parameter beyond which the Rosenzweig model is stable and may be used as a potential agent to resolve PoE from a new perspective via fractional differential equations.

Peroxisome Proliferator-Activated Receptor γ (PPARγ) and Ligand Choreography: Newcomers Take the Stage.

PubMed

Garcia-Vallvé, Santiago; Guasch, Laura; Tomas-Hernández, Sarah; del Bas, Josep Maria; Ollendorff, Vincent; Arola, Lluís; Pujadas, Gerard; Mulero, Miquel

2015-07-23

Thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone, are peroxisome proliferator-activated receptor γ (PPARγ) full agonists that have been widely used in the treatment of type 2 diabetes mellitus. Despite the demonstrated beneficial effect of reducing glucose levels in the plasma, TZDs also induce several adverse effects. Consequently, the search for new compounds with potent antidiabetic effects but fewer undesired effects is an active field of research. Interestingly, the novel proposed mechanisms for the antidiabetic activity of PPARγ agonists, consisting of PPARγ Ser273 phosphorylation inhibition, ligand and receptor mutual dynamics, and the presence of an alternate binding site, have recently changed the view regarding the optimal characteristics for the screening of novel PPARγ ligands. Furthermore, transcriptional genomics could bring essential information about the genome-wide effects of PPARγ ligands. Consequently, facing the new mechanistic scenario proposed for these compounds is essential for resolving the paradoxes among their agonistic function, antidiabetic activities, and side effects and should allow the rational development of better and safer PPARγ-mediated antidiabetic drugs.

Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

PubMed Central

Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

2011-01-01

Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

Severe hypertriglyceridemia does not protect from ischemic brain injury in gene-modified hypertriglyceridemic mice.

PubMed

Chen, Yong; Liu, Ping; Qi, Rong; Wang, Yu-Hui; Liu, George; Wang, Chun

2016-05-15

Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke. To our surprise, infarct size, neurological deficits, brain edema, BBB permeability, neuron density and lipid peroxidation were the same in Tg-ApoCIII mice and Non-Tg mice after temporary middle cerebral artery occlusion (tMCAO). In the late phase (21 days after surgery), no differences were found in brain atrophy, neurological dysfunctions, weight and mortality between the two groups. To confirm the results in Tg-ApoCIII mice, Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1(GPIHBP1) knockout mice, another severe HTG mouse model, were used and yielded similar results. Our study demonstrates for the first time that extreme HTG does not affect ischemic brain injuries in the tMCAO mouse model, indicating that the association between HTG and good outcomes after ischemic stroke probably represents residual unmeasured confounding. Further clinical and prospective population-based studies are needed to explore variables that contribute to the paradox. Copyright © 2016 Elsevier B.V. All rights reserved.

Tunable regulation of CREB DNA binding activity couples genotoxic stress response and metabolism

PubMed Central

Kim, Sang Hwa; Trinh, Anthony T.; Larsen, Michele Campaigne; Mastrocola, Adam S.; Jefcoate, Colin R.; Bushel, Pierre R.; Tibbetts, Randal S.

2016-01-01

cAMP response element binding protein (CREB) is a key regulator of glucose metabolism and synaptic plasticity that is canonically regulated through recruitment of transcriptional coactivators. Here we show that phosphorylation of CREB on a conserved cluster of Ser residues (the ATM/CK cluster) by the DNA damage-activated protein kinase ataxia-telangiectasia-mutated (ATM) and casein kinase1 (CK1) and casein kinase2 (CK2) positively and negatively regulates CREB-mediated transcription in a signal dependent manner. In response to genotoxic stress, phosphorylation of the ATM/CK cluster inhibited CREB-mediated gene expression, DNA binding activity and chromatin occupancy proportional to the number of modified Ser residues. Paradoxically, substoichiometric, ATM-independent, phosphorylation of the ATM/CK cluster potentiated bursts in CREB-mediated transcription by promoting recruitment of the CREB coactivator, cAMP-regulated transcriptional coactivators (CRTC2). Livers from mice expressing a non-phosphorylatable CREB allele failed to attenuate gluconeogenic genes in response to DNA damage or fully activate the same genes in response to glucagon. We propose that phosphorylation-dependent regulation of DNA binding activity evolved as a tunable mechanism to control CREB transcriptional output and promote metabolic homeostasis in response to rapidly changing environmental conditions. PMID:27431323

Quantum Quasi-Paradoxes and Quantum Sorites Paradoxes

NASA Astrophysics Data System (ADS)

Smarandache, Florentin

2009-03-01

There can be generated many paradoxes or quasi-paradoxes that may occur from the combination of quantum and non-quantum worlds in physics. Even the passage from the micro-cosmos to the macro-cosmos, and reciprocally, can generate unsolved questions or counter-intuitive ideas. We define a quasi-paradox as a statement which has a prima facie self-contradictory support or an explicit contradiction, but which is not completely proven as a paradox. We present herein four elementary quantum quasi-paradoxes and their corresponding quantum Sorites paradoxes, which form a class of quantum quasi-paradoxes.

Who really pays for health insurance? The incidence of employer-provided health insurance with sticky nominal wages.

PubMed

Sommers, Benjamin D

2005-03-01

This paper addresses two seeming paradoxes in the realm of employer-provided health insurance: First, businesses consistently claim that they bear the burden of the insurance they provide for employees, despite theory and empirical evidence indicating that workers bear the full incidence. Second, benefit generosity and the percentage of premiums paid by employers have decreased in recent decades, despite the preferential tax treatment of employer-paid benefits relative to wages-trends unexplained by the standard incidence model. This paper offers a revised incidence model based on nominal wage rigidity, in an attempt to explain these paradoxes. The model predicts that when the nominal wage constraint binds, some of the burden of increasing insurance premiums will fall on firms, particularly small companies with low-wage employees. In response, firms will reduce employment, decrease benefit generosity, and require larger employee premium contributions. Using Current Population Survey data from 2000-2001, I find evidence for this kind of wage rigidity and its associated impact on the employment and premium contributions of low-wage insured workers during a period of rapid premium growth.

Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox.

PubMed

Lavie, Carl J; McAuley, Paul A; Church, Timothy S; Milani, Richard V; Blair, Steven N

2014-04-15

Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrated an association of mild obesity and, particularly, overweight on improved survival. We review in detail the obesity paradox in CV diseases where overweight and at least mildly obese patients with most CV diseases seem to have a better prognosis than do their leaner counterparts. The implications of cardiorespiratory fitness with prognosis are discussed, along with the joint impact of fitness and adiposity on the obesity paradox. Finally, in light of the obesity paradox, the potential value of purposeful weight loss and increased physical activity to affect levels of fitness is reviewed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Geologic characterization report for the Paradox Basin Study Region, Utah Study Areas. Volume 6: Salt Valley

NASA Astrophysics Data System (ADS)

1984-12-01

Surface landforms in the Salt Valley Area are generally a function of the Salt Valley anticline and are characterized by parallel and subparallel cuestaform ridges and hogbacks and flat valley floors. The most prominent structure in the Area is the Salt Valley anticline. Erosion resulting from the Tertiary uplift of the Colorado Plateau led to salt dissolution and subsequent collapse along the crest of the anticline. Continued erosion removed the collapse material, forming an axial valley along the crest of the anticline. Paleozoic rocks beneath the salt bearing Paradox Formation consist of limestone, dolomite, sandstone, siltstone and shale. The salt beds of the Paradox formation occur in distinct cycles separated by an interbed sequence of anhydrite, carbonate, and clastic rocks. The Paradox Formation is overlain by Pennsylvanian limestone; Permian sandstone; and Mesozoic sandstone, mudstone, conglomerate and shale. No earthquakes have been reported in the area during the period of the historic record and contemporary seismicity appears to be diffusely distributed, of low level and small magnitude. The upper unit includes the Permian strata and upper Honaker trail formation.

Measurement and validation of the nature of salivary adiponectin.

PubMed

Akuailou, Eleonore-N; Vijayagopal, Parakat; Imrhan, Victorine; Prasad, Chandan

2013-10-01

Adiponectin (Ad) is an adipocyte-derived hormone that plays an essential role in regulating insulin sensitivity, inflammation, and atherogenesis. Levels of some hormones in saliva change in a fashion similar to that in plasma in response to a disease or physiological condition. Since saliva is an easy to obtain biological fluid, measurements of salivary hormonal changes are preferred in diagnoses and treatments. Therefore, it was of interest to examine the nature of salivary Ad. While there have been two publications in the literature reporting presence of Ad in human saliva, the nature of salivary Ad has not been characterized. To this end, we investigated the effect of sample dilution on the measurement of Ad in saliva. To our surprise, we observed an increase in measurable level of Ad in saliva on sample dilution. One explanation for this paradoxical observation may be the presence of inhibitor(s) of Ad/anti-Ad binding in saliva that following dilution relieves the inhibitory effect. Working with this hypothesis, we were able to demonstrate the presence of an inhibitor in saliva that co-eluted with the dimeric form of Ad and was capable of inhibiting Ad assay. The presence of such inhibitor(s) may lead to underestimation of Ad in saliva.

Prolonged Fasting Identifies Heat Shock Protein 10 as a Sirtuin 3 Substrate

PubMed Central

Lu, Zhongping; Chen, Yong; Aponte, Angel M.; Battaglia, Valentina; Gucek, Marjan; Sack, Michael N.

2015-01-01

Although Sirtuin 3 (SIRT3), a mitochondrially enriched deacetylase and activator of fat oxidation, is down-regulated in response to high fat feeding, the rate of fatty acid oxidation and mitochondrial protein acetylation are invariably enhanced in this dietary milieu. These paradoxical data implicate that additional acetylation modification-dependent levels of regulation may be operational under nutrient excess conditions. Because the heat shock protein (Hsp) Hsp10-Hsp60 chaperone complex mediates folding of the fatty acid oxidation enzyme medium-chain acyl-CoA dehydrogenase, we tested whether acetylation-dependent mitochondrial protein folding contributes to this regulatory discrepancy. We demonstrate that Hsp10 is a functional SIRT3 substrate and that, in response to prolonged fasting, SIRT3 levels modulate mitochondrial protein folding. Acetyl mutagenesis of Hsp10 lysine 56 alters Hsp10-Hsp60 binding, conformation, and protein folding. Consistent with Hsp10-Hsp60 regulation of fatty acid oxidation enzyme integrity, medium-chain acyl-CoA dehydrogenase activity and fat oxidation are elevated by Hsp10 acetylation. These data identify acetyl modification of Hsp10 as a nutrient-sensing regulatory node controlling mitochondrial protein folding and metabolic function. PMID:25505263

Nitric-oxide Synthase Forms N-NO-pterin and S-NO-Cys

PubMed Central

Rosenfeld, Robin J.; Bonaventura, Joseph; Szymczyna, Blair R.; MacCoss, Michael J.; Arvai, Andrew S.; Yates, John R.; Tainer, John A.; Getzoff, Elizabeth D.

2010-01-01

Inducible nitric-oxide synthase (iNOS) produces biologically stressful levels of nitric oxide (NO) as a potent mediator of cellular cytotoxicity or signaling. Yet, how this nitrosative stress affects iNOS function in vivo is poorly understood. Here we define two specific non-heme iNOS nitrosation sites discovered by combining UV-visible spectroscopy, chemiluminescence, mass spectrometry, and x-ray crystallography. We detected auto-S-nitrosylation during enzymatic turnover by using chemiluminescence. Selective S-nitrosylation of the ZnS4 site, which bridges the dimer interface, promoted a dimer-destabilizing order-to-disorder transition. The nitrosated iNOS crystal structure revealed an unexpected N-NO modification on the pterin cofactor. Furthermore, the structurally defined N-NO moiety is solvent-exposed and available to transfer NO to a partner. We investigated glutathione (GSH) as a potential transnitrosation partner because the intracellular GSH concentration is high and NOS can form S-nitrosoglutathione. Our computational results predicted a GSH binding site adjacent to the N-NO-pterin. Moreover, we detected GSH binding to iNOS with saturation transfer difference NMR spectroscopy. Collectively, these observations resolve previous paradoxes regarding this uncommon pterin cofactor in NOS and suggest means for regulating iNOS activity via N-NO-pterin and S-NO-Cys modifications. The iNOS self-nitrosation characterized here appears appropriate to help control NO production in response to cellular conditions. PMID:20659888

Genetic inactivation of glutamate neurons in the rat sublaterodorsal tegmental nucleus recapitulates REM sleep behaviour disorder.

PubMed

Valencia Garcia, Sara; Libourel, Paul-Antoine; Lazarus, Michael; Grassi, Daniela; Luppi, Pierre-Hervé; Fort, Patrice

2017-02-01

SEE SCHENCK AND MAHOWALD DOI101093/AWW329 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Idiopathic REM sleep behaviour disorder is characterized by the enactment of violent dreams during paradoxical (REM) sleep in the absence of normal muscle atonia. Accumulating clinical and experimental data suggest that REM sleep behaviour disorder might be due to the neurodegeneration of glutamate neurons involved in paradoxical sleep and located within the pontine sublaterodorsal tegmental nucleus. The purpose of the present work was thus to functionally determine first, the role of glutamate sublaterodorsal tegmental nucleus neurons in paradoxical sleep and second, whether their genetic inactivation is sufficient for recapitulating REM sleep behaviour disorder in rats. For this goal, we first injected two retrograde tracers in the intralaminar thalamus and ventral medulla to disentangle neuronal circuits in which sublaterodorsal tegmental nucleus is involved; second we infused bilaterally in sublaterodorsal tegmental nucleus adeno-associated viruses carrying short hairpin RNAs targeting Slc17a6 mRNA [which encodes vesicular glutamate transporter 2 (vGluT2)] to chronically impair glutamate synaptic transmission in sublaterodorsal tegmental nucleus neurons. At the neuroanatomical level, sublaterodorsal tegmental nucleus neurons specifically activated during paradoxical sleep hypersomnia send descending efferents to glycine/GABA neurons within the ventral medulla, but not ascending projections to the intralaminar thalamus. These data suggest a crucial role of sublaterodorsal tegmental nucleus neurons rather in muscle atonia than in paradoxical sleep generation. In line with this hypothesis, 30 days after adeno-associated virus injections into sublaterodorsal tegmental nucleus rats display a decrease of 30% of paradoxical sleep daily quantities, and a significant increase of muscle tone during paradoxical sleep concomitant to a tremendous increase of abnormal motor dream-enacting behaviours. These animals display symptoms and behaviours during paradoxical sleep that closely mimic human REM sleep behaviour disorder. Altogether, our data demonstrate that glutamate sublaterodorsal tegmental nucleus neurons generate muscle atonia during paradoxical sleep likely through descending projections to glycine/GABA premotor neurons in the ventral medulla. Although playing a role in paradoxical sleep regulation, they are, however, not necessary for inducing the state itself. The present work further validates a potent new preclinical REM sleep behaviour disorder model that opens avenues for studying and treating this disabling sleep disorder, and advances potential regions implicated in prodromal stages of synucleinopathies such as Parkinson's disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is Attenuated by Resistance Training.

PubMed

Giampá, Sara Quaglia de Campos; Mônico-Neto, Marcos; de Mello, Marco Tulio; Souza, Helton de Sá; Tufik, Sergio; Lee, Kil Sun; Koike, Marcia Kiyomi; Dos Santos, Alexandra Alberta; Antonio, Ednei Luiz; Serra, Andrey Jorge; Tucci, Paulo José Ferreira; Antunes, Hanna Karen Moreira

2016-01-01

Paradoxical sleep deprivation activates the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with the cardiovascular system. The beneficial effects of resistance training are related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that resistance training can prevent the cardiac remodeling and dysfunction caused by paradoxical sleep deprivation. Male Wistar rats were distributed into four groups: control (C), resistance training (RT), paradoxical sleep deprivation for 96 hours (PSD96) and both resistance training and sleep deprivation (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac histomorphometry, hormonal profile and molecular analysis were evaluated. Compared to the C group, PSD96 group had a higher left ventricular systolic pressure, heart rate and left atrium index. In contrast, the left ventricle systolic area and the left ventricle cavity diameter were reduced in the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these alterations, reduced levels of serum testosterone and insulin-like growth factor-1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed in the PSD96 group. Prophylactic resistance training attenuated most of these changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins involved in the pathologic cardiac hypertrophy pathway. Resistance training effectively attenuates cardiac dysfunction and hormonal imbalance induced by paradoxical sleep deprivation.

AngioVac Aspiration for Paradoxical Emboli Protection through a Fenestrated Fontan During Central Venous Thrombus Manipulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Hakim, Ramsey, E-mail: ralhakim@mednet.ucla.edu; Patel, Komal, E-mail: kdpatel@mednet.ucla.edu; Moriarty, John M., E-mail: jmoriarty@mednet.ucla.edu

2015-06-15

This case reports describes a 39-year-old female with a history of surgically repaired hypoplastic left heart syndrome who presented with a left peripherally inserted central catheter (PICC) with associated large volume subclavian and brachiocephalic vein thrombus. Due to the presence of a right-to-left shunt via a fenestrated Fontan, there was clinical concern for a paradoxical embolism during removal of the PICC. The AngioVac aspiration system was successfully utilized to aspirate thromboemboli from the level of the proximal Glenn shunt during manipulation and removal of the PICC. This is the first reported case to demonstrate the safe and effective use ofmore » the AngioVac aspiration system for protection of paradoxical emboli through a cardiac right-to-left shunt during a procedure at high risk for thromboembolism.« less

AngioVac Aspiration for Paradoxical Emboli Protection through a Fenestrated Fontan During Central Venous Thrombus Manipulation.

PubMed

Al-Hakim, Ramsey; Patel, Komal; Moriarty, John M

2015-06-01

This case reports describes a 39-year-old female with a history of surgically repaired hypoplastic left heart syndrome who presented with a left peripherally inserted central catheter (PICC) with associated large volume subclavian and brachiocephalic vein thrombus. Due to the presence of a right-to-left shunt via a fenestrated Fontan, there was clinical concern for a paradoxical embolism during removal of the PICC. The AngioVac aspiration system was successfully utilized to aspirate thromboemboli from the level of the proximal Glenn shunt during manipulation and removal of the PICC. This is the first reported case to demonstrate the safe and effective use of the AngioVac aspiration system for protection of paradoxical emboli through a cardiac right-to-left shunt during a procedure at high risk for thromboembolism.

A non-canonical mechanism for Crm1-export cargo complex assembly.

PubMed

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Faza, Marius Boulos; Panse, Vikram Govind

2015-04-21

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

Paradoxical enhancement of chemoreceptor detection sensitivity by a sensory adaptation enzyme

PubMed Central

Han, Xue-Sheng; Dahlquist, Frederick W.; Parkinson, John S.

2017-01-01

A sensory adaptation system that tunes chemoreceptor sensitivity enables motile Escherichia coli cells to track chemical gradients with high sensitivity over a wide dynamic range. Sensory adaptation involves feedback control of covalent receptor modifications by two enzymes: CheR, a methyltransferase, and CheB, a methylesterase. This study describes a CheR function that opposes the signaling consequences of its catalytic activity. In the presence of CheR, a variety of mutant serine chemoreceptors displayed up to 40-fold enhanced detection sensitivity to chemoeffector stimuli. This response enhancement effect did not require the known catalytic activity of CheR, but did involve a binding interaction between CheR and receptor molecules. Response enhancement was maximal at low CheR:receptor stoichiometry and quantitative analyses argued against a reversible binding interaction that simply shifts the ON–OFF equilibrium of receptor signaling complexes. Rather, a short-lived CheR binding interaction appears to promote a long-lasting change in receptor molecules, either a covalent modification or conformation that enhances their response to attractant ligands. PMID:28827352

Out of place, out of mind: Schema-driven false memory effects for object-location bindings.

PubMed

Lew, Adina R; Howe, Mark L

2017-03-01

Events consist of diverse elements, each processed in specialized neocortical networks, with temporal lobe memory systems binding these elements to form coherent event memories. We provide a novel theoretical analysis of an unexplored consequence of the independence of memory systems for elements and their bindings, 1 that raises the paradoxical prediction that schema-driven false memories can act solely on the binding of event elements despite the superior retrieval of individual elements. This is because if 2, or more, schema-relevant elements are bound together in unexpected conjunctions, the unexpected conjunction will increase attention during encoding to both the elements and their bindings, but only the bindings will receive competition with evoked schema-expected bindings. We test our model by examining memory for object-location bindings in recognition (Study 1) and recall (Studies 2 and 3) tasks. After studying schema-relevant objects in unexpected locations (e.g., pan on a stool in a kitchen scene), participants who then viewed these objects in expected locations (e.g., pan on stove) at test were more likely to falsely remember this object-location pairing as correct, compared with participants that viewed a different unexpected object-location pairing (e.g., pan on floor). In recall, participants were more likely to correctly remember individual schema-relevant objects originally viewed in unexpected, as opposed to expected locations, but were then more likely to misplace these items in the original room scene to expected places, relative to control schema-irrelevant objects. Our theoretical analysis and novel paradigm provide a tool for investigating memory distortions acting on binding processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Measles Virus (MV) Nucleoprotein Binds to a Novel Cell Surface Receptor Distinct from FcγRII via Its C-Terminal Domain: Role in MV-Induced Immunosuppression

PubMed Central

Laine, David; Trescol-Biémont, Marie-Claude; Longhi, Sonia; Libeau, Geneviève; Marie, Julien C.; Vidalain, Pierre-Olivier; Azocar, Olga; Diallo, Adama; Canard, Bruno; Rabourdin-Combe, Chantal; Valentin, Hélène

2003-01-01

During acute measles virus (MV) infection, an efficient immune response occurs, followed by a transient but profound immunosuppression. MV nucleoprotein (MV-N) has been reported to induce both cellular and humoral immune responses and paradoxically to account for immunosuppression. Thus far, this latter activity has been attributed to MV-N binding to human and murine FcγRII. Here, we show that apoptosis of MV-infected human thymic epithelial cells (TEC) allows the release of MV-N in the extracellular compartment. This extracellular N is then able to bind either to MV-infected or uninfected TEC. We show that recombinant MV-N specifically binds to a membrane protein receptor, different from FcγRII, highly expressed on the cell surface of TEC. This new receptor is referred to as nucleoprotein receptor (NR). In addition, different Ns from other MV-related morbilliviruses can also bind to FcγRII and/or NR. We show that the region of MV-N responsible for binding to NR maps to the C-terminal fragment (NTAIL). Binding of MV-N to NR on TEC triggers sustained calcium influx and inhibits spontaneous cell proliferation by arresting cells in the G0 and G1 phases of the cell cycle. Finally, MV-N binds to both constitutively expressed NR on a large spectrum of cells from different species and to human activated T cells, leading to suppression of their proliferation. These results provide evidence that MV-N, after release in the extracellular compartment, binds to NR and thereby plays a role in MV-induced immunosuppression. PMID:14557619

Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox

PubMed Central

Tu, Yu-Kang; Gunnell, David; Gilthorpe, Mark S

2008-01-01

This article discusses three statistical paradoxes that pervade epidemiological research: Simpson's paradox, Lord's paradox, and suppression. These paradoxes have important implications for the interpretation of evidence from observational studies. This article uses hypothetical scenarios to illustrate how the three paradoxes are different manifestations of one phenomenon – the reversal paradox – depending on whether the outcome and explanatory variables are categorical, continuous or a combination of both; this renders the issues and remedies for any one to be similar for all three. Although the three statistical paradoxes occur in different types of variables, they share the same characteristic: the association between two variables can be reversed, diminished, or enhanced when another variable is statistically controlled for. Understanding the concepts and theory behind these paradoxes provides insights into some controversial or contradictory research findings. These paradoxes show that prior knowledge and underlying causal theory play an important role in the statistical modelling of epidemiological data, where incorrect use of statistical models might produce consistent, replicable, yet erroneous results. PMID:18211676

Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F

PubMed Central

Shaw, Alice T.; Friboulet, Luc; Leshchiner, Ignaty; Gainor, Justin F.; Bergqvist, Simon; Brooun, Alexei; Burke, Benjamin J.; Deng, Ya-Li; Liu, Wei; Dardaei, Leila; Frias, Rosa L.; Schultz, Kate R.; Logan, Jennifer; James, Leonard P.; Smeal, Tod; Timofeevski, Sergei; Katayama, Ryohei; Iafrate, A. John; Le, Long; McTigue, Michele; Getz, Gad

2016-01-01

Summary In a patient who had metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK kinase domain. This mutation is predicted to result in a substitution of cysteine by tyrosine at amino acid residue 1156 (C1156Y). Her tumor did not respond to a second-generation ALK inhibitor, but it did respond to lorlatinib (PF-06463922), a third-generation inhibitor. When her tumor relapsed, sequencing of the resistant tumor revealed an ALK L1198F mutation in addition to the C1156Y mutation. The L1198F substitution confers resistance to lorlatinib through steric interference with drug binding. However, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitizing resistant cancers to crizotinib. The patient received crizotinib again, and her cancer-related symptoms and liver failure resolved. PMID:26698910

TALE proteins search DNA using a rotationally decoupled mechanism.

PubMed

Cuculis, Luke; Abil, Zhanar; Zhao, Huimin; Schroeder, Charles M

2016-10-01

Transcription activator-like effector (TALE) proteins are a class of programmable DNA-binding proteins used extensively for gene editing. Despite recent progress, however, little is known about their sequence search mechanism. Here, we use single-molecule experiments to study TALE search along DNA. Our results show that TALEs utilize a rotationally decoupled mechanism for nonspecific search, despite remaining associated with DNA templates during the search process. Our results suggest that the protein helical structure enables TALEs to adopt a loosely wrapped conformation around DNA templates during nonspecific search, facilitating rapid one-dimensional (1D) diffusion under a range of solution conditions. Furthermore, this model is consistent with a previously reported two-state mechanism for TALE search that allows these proteins to overcome the search speed-stability paradox. Taken together, our results suggest that TALE search is unique among the broad class of sequence-specific DNA-binding proteins and supports efficient 1D search along DNA.

Paradoxical Growth of Candida albicans in the Presence of Caspofungin Is Associated with Multiple Cell Wall Rearrangements and Decreased Virulence

PubMed Central

Rueda, Cristina; Cuenca-Estrella, Manuel

2014-01-01

In the last decade, echinocandins have emerged as an important family of antifungal drugs because of their fungicidal activity against Candida spp. Echinocandins inhibit the enzyme β-1,3-d-glucan synthase, encoded by the FKS genes, and resistance to echinocandins is associated with mutations in this gene. In addition, echinocandin exposure can produce paradoxical growth, defined as the ability to grow at high antifungal concentrations but not at intermediate concentrations. In this work, we have demonstrated that paradoxical growth of Candida albicans in the presence of caspofungin is not due to antifungal degradation or instability. Media with high caspofungin concentrations recovered from wells where C. albicans showed paradoxical growth inhibited the growth of a Candida krusei reference strain. Cells exhibiting paradoxical growth at high caspofungin concentrations showed morphological changes such as enlarged size, abnormal septa, and absence of filamentation. Chitin content increased from the MIC to high caspofungin concentrations. Despite the high chitin levels, around 23% of cells died after treatment with caspofungin, indicating that chitin is required but not sufficient to protect the cells from the fungicidal effect of caspofungin. Moreover, we found that after paradoxical growth, β-1,3-glucan was exposed at the cell wall surface. Cells grown at high caspofungin concentrations had decreased virulence in the invertebrate host Galleria mellonella. Cells grown at high caspofungin concentrations also induced a proinflammatory response in murine macrophages compared to control cells. Our work highlights important aspects about fungal adaptation to caspofungin, and although this adaptation is associated with reduced virulence, the clinical implications remain to be elucidated. PMID:24295973

MRI in France: the French paradox.

PubMed

Lavayssière, R; Cabée, A E

2001-04-01

Although France is a modern, developed country, which spends nearly 10% of the gross national product on healthcare and has a highly praised level of medicine, the number of modern imaging scanners, such as CT (595), MRI (182), and PET (5), is quite low when compared to other European countries. Politics and a long-standing tradition of centralization are prominent among reasons for such an underdevelopment. This situation has resulted in another French paradox not linked to wine consumption. The French life expectancy is very high, but the number of imaging equipment is very low.

Obesity paradox and mortality in adults with and without incident type 2 diabetes: a matched population-level cohort study

PubMed Central

Badrick, Ellena; Sperrin, Matthew; Buchan, Iain E

2017-01-01

Objective Among adults with type 2 diabetes (T2D), several (but not all) studies show that being overweight (body mass index (BMI): 25.0–29.9 kg/m2) or obese I (BMI: 30.0–34.9 kg/m2) near the time of diagnosis, is unexpectedly associated with reduced all-cause mortality compared with normal weight—the obesity paradox. We addressed whether this observation is causal (eg, a true protective effect); due to confounding (including effect modification); or due to selection (‘collider’) bias. Research design and methods We performed a matched population-level cohort study using primary care records from Salford, UK (1995–2012) in 10 464 patients with incident T2D paired (1:3) with 31 020 individuals who never developed T2D. We estimated HRs for associations of BMI with all-cause mortality using Cox models, stratified by smoking status. Results Median follow-up was 8.7 years. For never smokers, the hazard of all-cause mortality increased from 25 kg/m2, in a linear manner, with increasing BMI in the T2D cohort (HR per 5 kg/m2: 1.23, ptrend<0.001) and in the non-diabetes cohort (HR per 5 kg/m2: 1.34, ptrend<0.001). In contrast, among ever smokers, BMI-mortality relationships were U-shaped in the T2D and non-diabetes cohorts. Evidence of the obesity paradox in ever smokers, with and without T2D, argued against a selection bias, but supported a contribution of effect modification by smoking (pinteraction=0.009). Results were stable to various sensitivity analyses. Conclusions In this cohort, the obesity paradox is mainly explained by smoking as an effect modifier. These findings indicate that the obesity paradox does not challenge standard weight management recommendations among T2D patients. PMID:28321314

On akrasia and the "prevention paradox".

PubMed

Petrini, C

The term akrasia describes the behaviour of persons who knowingly and consciously act against their better judgement and is exemplified by various unhealthy lifestyle choices. Prevention should aim to provide guidance in the choice of lifestyle. While at the individual level this is best directed towards those who are at high risk, at a general population level it is preferable to target the higher numbers of individuals at low risk rather than the fewer high-risk subjects. This is the so-called "prevention paradox". From an ethical viewpoint it is important, when planning measures to maximise the benefits for the community, not to neglect individual subjects: the common good is created by promoting and making the most of the good of the individual.

Beyond Parrondo's Paradox

PubMed Central

SHU, Jian-Jun; WANG, Qi-Wen

2014-01-01

The Parrondo's paradox is a counterintuitive phenomenon where individually-losing strategies can be combined in producing a winning expectation. In this paper, the issues surrounding the Parrondo's paradox are investigated. The focus is lying on testifying whether the same paradoxical effect can be reproduced by using a simple capital dependent game. The paradoxical effect generated by the Parrondo's paradox can be explained by placing all the parameters in one probability space. Based on this framework, it is able to generate other possible paradoxical effects by manipulating the parameters in the probability space. PMID:24577586

Isolation and characterization of mutants with lesions affecting pellicle formation and erythrocyte agglutination by type 1 piliated Escherichia coli.

PubMed Central

Harris, S L; Elliott, D A; Blake, M C; Must, L M; Messenger, M; Orndorff, P E

1990-01-01

The product of the pilE (also called fimH) gene is a minor component of type 1 pili in Escherichia coli. Mutants that have insertions in the pilE gene are fully piliated but unable to bind to and agglutinate guinea pig erythrocytes, a characteristic of wild-type type 1 piliated E. coli. In this paper we describe the isolation of 48 mutants with point lesions that map to the pilE gene. Such mutants were isolated by using mutT mutagenesis and an enrichment procedure devised to favor the growth of individuals that could form a pellicle in static broth containing alpha-methylmannoside, an inhibitor of erythrocyte binding and pellicle formation. Results indicated that the enrichment favored mutants expressing pilE gene products that were defective in mediating erythrocyte binding. Characterization of 12 of the mutants in greater detail revealed that certain lesions affected pilus number and length. In addition, a mutant that was temperature sensitive for erythrocyte binding was isolated and used to provide evidence that pellicle formation relies on the intercellular interaction of pilE gene products. Our results suggest a molecular explanation for the old and paradoxical observations connecting pellicle formation and erythrocyte agglutination by type 1 piliated E. coli. Images PMID:1977736

The absence of birthweight paradox as a marker of disadvantages faced by low maternal education children.

PubMed

Guimarães, P V; Fonseca, S C; Pinheiro, R S; Aguiar, F P; Camargo, K R; Coeli, C M

2017-12-01

This study tested the hypothesis that the birthweight paradox would not be observed when assessing the effect of maternal education on neonatal mortality in the presence of socioeconomic inequality in access to health care. Non-concurrent cohort study. Passive follow-up of live-born infants using probabilistic record linkage of birth and death records for Rio de Janeiro (2004-2010; n = 1 445 367). Maternal age, birthweight and neonatal death were evaluated according to maternal educational level strata (<4, 4-11 and ≥12 years of study). We estimated the association between maternal educational level and neonatal mortality using logistical regression models adjusted for maternal age and birthweight (<2500 g and ≥2500 g). Neonatal mortality was 1.8 times higher in low educational level group compared with high educational level. We did not find birthweight-specific mortality curves crossing over in the stratum under 2500 g (birthweight paradox). The odds of a low birthweight child being born in facilities without neonatal intensive care units was about 70% higher in the group of low education when compared with mothers with high education. The absence of crossing birthweight-specific mortality curves may be a reason for concern about the severity of the disadvantages faced by low maternal education women. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Differentially expressed microRNAs in lung adenocarcinoma invert effects of copy number aberrations of prognostic genes

PubMed Central

Tokar, Tomas; Pastrello, Chiara; Ramnarine, Varune R.; Zhu, Chang-Qi; Craddock, Kenneth J.; Pikor, Larrisa A.; Vucic, Emily A.; Vary, Simon; Shepherd, Frances A.; Tsao, Ming-Sound; Lam, Wan L.; Jurisica, Igor

2018-01-01

In many cancers, significantly down- or upregulated genes are found within chromosomal regions with DNA copy number alteration opposite to the expression changes. Generally, this paradox has been overlooked as noise, but can potentially be a consequence of interference of epigenetic regulatory mechanisms, including microRNA-mediated control of mRNA levels. To explore potential associations between microRNAs and paradoxes in non-small-cell lung cancer (NSCLC) we curated and analyzed lung adenocarcinoma (LUAD) data, comprising gene expressions, copy number aberrations (CNAs) and microRNA expressions. We integrated data from 1,062 tumor samples and 241 normal lung samples, including newly-generated array comparative genomic hybridization (aCGH) data from 63 LUAD samples. We identified 85 “paradoxical” genes whose differential expression consistently contrasted with aberrations of their copy numbers. Paradoxical status of 70 out of 85 genes was validated on sample-wise basis using The Cancer Genome Atlas (TCGA) LUAD data. Of these, 41 genes are prognostic and form a clinically relevant signature, which we validated on three independent datasets. By meta-analysis of results from 9 LUAD microRNA expression studies we identified 24 consistently-deregulated microRNAs. Using TCGA-LUAD data we showed that deregulation of 19 of these microRNAs explains differential expression of the paradoxical genes. Our results show that deregulation of paradoxical genes is crucial in LUAD and their expression pattern is maintained epigenetically, defying gene copy number status. PMID:29507679

Testing the Latino paradox in Latin America: a population-based study of Intra-regional immigrants in Chile.

PubMed

Cabieses, Baltica; Tunstall, Helena; Pickett, Kate

2013-10-01

Several studies in high-income countries report better health status of immigrants compared to the local population ("healthy migrant" effect), regardless of their socioeconomic deprivation. This is known as the Latino paradox. To test the Latino paradox within Latin America by assessing the health of international immigrants to Chile, most of them from Latin American countries, and comparing them to the Chilean-born. Secondary data analysis of the population-based CASEN survey-2006. Three health outcomes were included: disability, illness/accident, and cancer/chronic condition (dichotomous). Demographics (age, sex, marital status, urban/rural, ethnicity), socioeconomic-status (SES: educational level, employment status and household income per-capita), and material standards (overcrowding, sanitation, housing quality). Crude and adjusted weighted regression models were performed. One percent of Chile's population were immigrants, mainly from other Latin American countries. A "healthy migrant" effect appeared within the total immigrant population: this group had a significantly lower crude prevalence of almost all health indicators than the Chilean-born, which remained after adjusting for various demographic characteristics. However, this effect lost significance when adjusting by SES for most outcomes. The Latino paradox was not observed for international immigrants compared to the local population in Chile. Also, health of immigrants with the longest time of residency showed similar health rates to the Chilean-born. The Latino paradox was not observed in Chile. Protecting low SES immigrants in Chile could have large positive effects in their health at arrival and over time.

The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox".

PubMed

Ito, Ryuichi; Narita, Shintaro; Huang, Mingguo; Nara, Taketoshi; Numakura, Kazuyuki; Takayama, Koichiro; Tsuruta, Hiroshi; Maeno, Atsushi; Saito, Mitsuru; Inoue, Takamitsu; Tsuchiya, Norihiko; Satoh, Shigeru; Habuchi, Tomonori

2017-01-01

Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this "obesity paradox" is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively). Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035). There was a weak inverse correlation between sAd level and BMI in RCC patients (r = -0.344, p = 0.002). Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035). Adiponectin levels in perinephric adipose tissue and intratumoral AdipoR1/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-O and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation- and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the "obesity paradox" of RCC.

Client cognitive responses to counselor paradoxical and nonparadoxical directives.

PubMed

Lee, D Y; Rossiter, B; Martin, J; Uhlemann, M R

1990-09-01

Client cognitive responses to counselor paradoxical and nonparadoxical directives were examined. It was predicted (a) that clients who received paradoxical symptom prescriptions would display a greater negativity toward the counselor and counseling than those who received nonparadoxical directives; and (b) that clients who received no rationale for the paradoxical directives would display a greater negativity than those who received a rationale. Thirty clients who had reported performance anxiety received one 45-minute counseling interview. Ten clients received paradoxical directives with a rationale, 10 received paradoxical directives with no rationale, and 10 received nonparadoxical directives. Results showed no significant differences in either client in-session negativity or out-of-session implementation of directives between the paradoxical and nonparadoxical conditions and between the rationale and no rationale paradoxical conditions. Possible implications of the findings are discussed.

Convective Lofting Links Indian Ocean Air Pollution to Paradoxical South Atlantic Ozone Maxima

NASA Technical Reports Server (NTRS)

Chatfield, Robert B.; Guan, Hong; Thompson, Anne M.; Witte, Jacquelyn C.

2003-01-01

We describe a broad resolution of the "Atlantic Paradox" concerning the seasonal and geographic distribution of tropical tropospheric ozone. We describe periods of significant maximum tropospheric O3 for Jan.-April, 1999, exploiting satellite estimates and SHADOZ (Southern Hemisphere Additional Ozonesondes). Trajectory analyses connecting sondes and Total Tropospheric Ozone (TTO)O3 maps suggest a complex influence from the Indian Ocean: beginning with mixed combustion sources, then low level transport, cumulonimbus venting, and finally high-level transport to the west, with possible mixing over Africa. For the Jan.- March highest column-O3 periods in the Atlantic, distinct sounding peaks trace to specific NO sources, especially lightning, while in the same episodes, recurring every 30 or 60 days, more diffuse buildups of Indian-to-Atlantic pollution make important contributions.

Rapid functional diversification in the structurally conserved ELAV family of neuronal RNA binding proteins

PubMed Central

Samson, Marie-Laure

2008-01-01

Background The Drosophila gene embryonic lethal abnormal visual system (elav) is the prototype of a gene family present in all metazoans. Its members encode structurally conserved neuronal proteins with three RNA Recognition Motifs (RRM) but they paradoxically act at diverse levels of post-transcriptional regulation. In an attempt to understand the history of this family, we searched for orthologs in eleven completely sequenced genomes, including those of humans, D. melanogaster and C. elegans, for which cDNAs are available. Results We analyzed 23 orthologs/paralogs of elav, and found evidence of gain/loss of gene copy number. For one set of genes, including elav itself, the coding sequences are free of introns and their products most resemble ELAV. The remaining genes show remarkable conservation of their exon organization, and their products most resemble FNE and RBP9, proteins encoded by the two elav paralogs of Drosophila. Remarkably, three of the conserved exon junctions are both close to structural elements, involved respectively in protein-RNA interactions and in the regulation of sub-cellular localization, and in the vicinity of diverse sequence variations. Conclusion The data indicate that the essential elav gene of Drosophila is newly emerged, restricted to dipterans and of retrotransposed origin. We propose that the conserved exon junctions constitute potential sites for sequence/function modifications, and that RRM binding proteins, whose function relies upon plastic RNA-protein interactions, may have played an important role in brain evolution. PMID:18715504

The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals.

PubMed

Kohler, Ines; Kouyos, Roger; Bianchi, Matteo; Grube, Christina; Wyrzucki, Arkadiusz; Günthard, Huldrych F; Hangartner, Lars

2015-09-10

HIV-positive individuals have lower antibody titers to influenza viruses than HIV-negative individuals, and the benefits of the annual vaccinations are controversially discussed. Also, there is no information about the breadth of the antibody response in HIV-infected individuals. The binding and neutralizing antibody titers to various human and nonhuman influenza A virus strain were determined in sera from 146 HIV-infected volunteers: They were compared with those found in 305 randomly selected HIV-negative donors, and put in relation to HIV-specific parameters. Univariable and multivariable regression was used to identify HIV-specific parameters associated with the measured binding and neutralizing activity. Enzyme-linked immunosorbent assays and in-vitro neutralization assays were used to determine the binding and neutralizing antibodiy titers to homo and heterosubtypic influenza A subtypes. We found that both homo and heterosubtypic antibody titers are lower in HIV-positive individuals. Vaccination promoted higher binding and neutralizing antibody titers to human but not to nonhuman isolates. HIV-induced immune damage (high viral load, low CD4 T-cell counts, and long untreated disease progression) is associated with impaired homosubtypic responses, but can have beneficial effects on the development of heterosubtypic antibodies, and an improved ratio of binding to neutralizing antibody titers to homosubtypic isolates. Our results indicate that repetitive vaccinations in HIV-positive individuals enhance antibody titers to human isolates. Interestingly, development of antibody titers to conserved heterosubtypic epitopes paradoxically appeared to profit from HIV-induced immune damage, as did the ratio of binding to neutralizing antibodies.

A "theory of relativity" for cognitive elasticity of time and modality dimensions supporting constant working memory capacity: involvement of harmonics among ultradian clocks?

PubMed

Glassman, R B

2000-02-01

1. The capacity of working memory (WM) for about 7+/-2 ("the magical number") serially organized simple verbal items may represent a fundamental constant of cognition. Indeed, there is the same capacity for sense of familiarity of a number of recently encountered places, observed in radial maze performance both of lab rats and of humans. 2. Moreover, both species show a peculiar capacity for retaining WM of place over delays. The literature also describes paradoxes of extended time duration in certain human verbal recall tasks. Certain bird species have comparable capacity for delayed recall of about 4 to 8 food caches in a laboratory room. 3. In addition to these paradoxes of the time dimension with WM (still sometimes called "short-term" memory) there are another set of paradoxes of dimensionality for human judgment of magnitudes, noted by Miller in his classic 1956 paper on "the magical number." We are able to reliably refer magnitudes to a rating scale of up to about seven divisions. Remarkably, that finding is largely independent of perceptual modality or even of the extent of a linear interval selected within any given modality. 4. These paradoxes suggest that "the magical number 7+/2" depends on fundamental properties of mammalian brains. 5. This paper theorizes that WM numerosity is conserved as a fundamental constant, by means of elasticity of cognitive dimensionality, including the temporal pace of arrival of significant items of cognitive information. 6. A conjectural neural code for WM item-capacity is proposed here, which extends the hypothetical principle of binding-by-synchrony. The hypothesis is that several coactive frequencies of brain electrical rhythms each mark a WM item. 7. If, indeed, WM does involve a brain wave frequency code (perhaps within the gamma frequency range that has often been suggested with the binding hypothesis) mathematical considerations suggest additional relevance of harmonic relationships. That is, if copresent sinusoids bear harmony-like ratios and are confined within a single octave, then they have fast temporal properties, while avoiding spurious difference rhythms. Therefore, if the present hypothesis is valid, it implies a natural limit on parallel processing of separate items in organismic brains. 8. Similar logic of periodic signals may hold for slower ultradian rhythms, including hypothetical ones that contribute to time-tagging and fresh sense of familiarity of a day's event memories. Similar logic may also hold for spatial periodic functions across brain tissue that, hypothetically, represent cognitive information. Thus, harmonic transitions among temporal and spatial periodic functions are a possible vehicle for the cognitive dimensional elasticity that conserves WM capacity. 9. Supporting roles are proposed of (a) basal ganglia, as a high-capacity cache for traces of recent experience temporarily suspended from active task-relevant processing and (b) of hippocampus as a phase and interval comparator for oscillating signals, whose spatiotemporal dynamics are topologically equivalent to a toroidal grid.

"Paradox of slow frequencies" - Are slow frequencies in upper cortical layers a neural predisposition of the level/state of consciousness (NPC)?

PubMed

Northoff, Georg

2017-09-01

Consciousness research has much focused on faster frequencies like alpha or gamma while neglecting the slower ones in the infraslow (0.001-0.1Hz) and slow (0.1-1Hz) frequency range. These slower frequency ranges have a "bad reputation" though; their increase in power can observed during the loss of consciousness as in sleep, anesthesia, and vegetative state. However, at the same time, slower frequencies have been conceived instrumental for consciousness. The present paper aims to resolve this paradox which I describe as "paradox of slow frequencies". I first show various data that suggest a central role of slower frequencies in integrating faster ones, i.e., "temporo-spatial integration and nestedness". Such "temporo-spatial integration and nestedness" is disrupted during the loss of consciousness as in anesthesia and sleep leading to "temporo-spatial fragmentation and isolation" between slow and fast frequencies. Slow frequencies are supposedly mediated by neural activity in upper cortical layers in higher-order associative regions as distinguished from lower cortical layers that are related to faster frequencies. Taken together, slower and faster frequencies take on different roles for the level/state of consciousness. Faster frequencies by themselves are sufficient and thus a neural correlate of consciousness (NCC) while slower frequencies are a necessary non-sufficient condition of possible consciousness, e.g., a neural predisposition of the level/state of consciousness (NPC). This resolves the "paradox of slow frequencies" in that it assigns different roles to slower and faster frequencies in consciousness, i.e., NCC and NPC. Taken as NCC and NPC, fast and slow frequencies including their relation as in "temporo-spatial integration and nestedness" can be considered a first "building bloc" of a future "temporo-spatial theory of consciousness" (TTC) (Northoff, 2013; Northoff, 2014b; Northoff & Huang, 2017). Copyright © 2017 Elsevier Inc. All rights reserved.

Rhodopsin TM6 Can Interact with Two Separate and Distinct Sites on Arrestin: Evidence for Structural Plasticity and Multiple Docking Modes in Arrestin–Rhodopsin Binding

PubMed Central

2015-01-01

Various studies have implicated the concave surface of arrestin in the binding of the cytosolic surface of rhodopsin. However, specific sites of contact between the two proteins have not previously been defined in detail. Here, we report that arrestin shares part of the same binding site on rhodopsin as does the transducin Gα subunit C-terminal tail, suggesting binding of both proteins to rhodopsin may share some similar underlying mechanisms. We also identify two areas of contact between the proteins near this region. Both sites lie in the arrestin N-domain, one in the so-called “finger” loop (residues 67–79) and the other in the 160 loop (residues 155–165). We mapped these sites using a novel tryptophan-induced quenching method, in which we introduced Trp residues into arrestin and measured their ability to quench the fluorescence of bimane probes attached to cysteine residues on TM6 of rhodopsin (T242C and T243C). The involvement of finger loop binding to rhodopsin was expected, but the evidence of the arrestin 160 loop contacting rhodopsin was not. Remarkably, our data indicate one site on rhodopsin can interact with multiple structurally separate sites on arrestin that are almost 30 Å apart. Although this observation at first seems paradoxical, in fact, it provides strong support for recent hypotheses that structural plasticity and conformational changes are involved in the arrestin–rhodopsin binding interface and that the two proteins may be able to interact through multiple docking modes, with arrestin binding to both monomeric and dimeric rhodopsin. PMID:24724832

DNA Length Modulates the Affinity of Fragments of Genomic DNA for the Nuclear Matrix In Vitro.

PubMed

García-Vilchis, David; Aranda-Anzaldo, Armando

2017-12-01

Classical observations have shown that during the interphase the chromosomal DNA of metazoans is organized in supercoiled loops attached to a compartment known as the nuclear matrix (NM). Fragments of chromosomal DNA able to bind the isolated NM in vitro are known as matrix associated/attachment/addressed regions or MARs. No specific consensus sequence or motif has been found that may constitute a universal, defining feature of MARs. On the other hand, high-salt resistant DNA-NM interactions in situ define true DNA loop anchorage regions or LARs, that might correspond to a subset of the potential MARs but are not necessarily identical to MARs characterized in vitro, since there are several examples of MARs able to bind the NM in vitro but which are not actually bound to the NM in situ. In the present work we assayed the capacity of two LARs, as well as of shorter fragments within such LARs, for binding to the NM in vitro. Paradoxically the isolated (≈2 kb) LARs cannot bind to the NM in vitro while their shorter (≈300 pb) sub-fragments and other non-related but equally short DNA fragments, bind to the NM in a high-salt resistant fashion. Our results suggest that the ability of a given DNA fragment for binding to the NM in vitro primarily depends on the length of the fragment, suggesting that binding to the NM is modulated by the local topology of the DNA fragment in suspension that it is known to depend on the DNA length. J. Cell. Biochem. 118: 4487-4497, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Rhodopsin TM6 can interact with two separate and distinct sites on arrestin: evidence for structural plasticity and multiple docking modes in arrestin-rhodopsin binding.

PubMed

Sinha, Abhinav; Jones Brunette, Amber M; Fay, Jonathan F; Schafer, Christopher T; Farrens, David L

2014-05-27

Various studies have implicated the concave surface of arrestin in the binding of the cytosolic surface of rhodopsin. However, specific sites of contact between the two proteins have not previously been defined in detail. Here, we report that arrestin shares part of the same binding site on rhodopsin as does the transducin Gα subunit C-terminal tail, suggesting binding of both proteins to rhodopsin may share some similar underlying mechanisms. We also identify two areas of contact between the proteins near this region. Both sites lie in the arrestin N-domain, one in the so-called "finger" loop (residues 67-79) and the other in the 160 loop (residues 155-165). We mapped these sites using a novel tryptophan-induced quenching method, in which we introduced Trp residues into arrestin and measured their ability to quench the fluorescence of bimane probes attached to cysteine residues on TM6 of rhodopsin (T242C and T243C). The involvement of finger loop binding to rhodopsin was expected, but the evidence of the arrestin 160 loop contacting rhodopsin was not. Remarkably, our data indicate one site on rhodopsin can interact with multiple structurally separate sites on arrestin that are almost 30 Å apart. Although this observation at first seems paradoxical, in fact, it provides strong support for recent hypotheses that structural plasticity and conformational changes are involved in the arrestin-rhodopsin binding interface and that the two proteins may be able to interact through multiple docking modes, with arrestin binding to both monomeric and dimeric rhodopsin.

[Differences in dynamics of insulin and insulin-like growth I (IGF-I) receptors internalization in isolated rat hepatocytes].

PubMed

Kolychev, A P; Ternovskaya, E E; Arsenieva, A V; Shapkina, E V

2013-01-01

Insulin and IGF-I are two related peptides performing in the mammalian body functionally different roles of the metabolic and growth hormones, respectively. Internalization of the insulin-receptor complex (IRC) is the most important chain of mechanism of the action of hormone. To elucidate differences in the main stages of internalization of the two related hormones, the internalization dynamics of 125I-insulin and 125I-IGF-I was traced in isolated rat hepatocytes at 37 and 12 degrees C. There were established marked differences in the process of internalization of labeled hormones, which is stimulated by insulin and IGF-I. At 37 degrees C the insulin-stimulated internalization, unlike the process initiated by IGF-I, did not reach the maximal level for 1 h of incubation. However, essential differences in the internalization course of these two related peptide were obvious at the temperature of 12 degrees C. The internalization level of insulin receptors at 12 degrees C decreased by one third in spite of a significant increase of the insulin receptor binding on the hepatocytes plasma membrane. At 12 degrees C a slight decrease of the proportion of intracellular 125I-IGF-I correlated with a decrease in the 125I-IGF-I binding to receptors on the cell membrane. Internalization of IGF-I receptors was not affected by low temperature, as neither its level, nor the rate changed at 12 degrees C. The paradoxical decrease of the insulin-stimulated internalization at low temperature seems to represent a peculiar "inhibition mechanism" of immersion of IRC into the cell, which leads to accumulation of the complexes on the cell surface and possibly to a readjustment of the insulin biological activity. The resistance of internalization of the IGF-I receptor to cold seems to be related to the more ancient origin of this mechanism in the poikilothermal vertebrates.

A non-canonical mechanism for Crm1-export cargo complex assembly

PubMed Central

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Boulos Faza, Marius; Panse, Vikram Govind

2015-01-01

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export. DOI: http://dx.doi.org/10.7554/eLife.05745.001 PMID:25895666

Obesity and poverty paradox in developed countries.

PubMed

Żukiewicz-Sobczak, Wioletta; Wróblewska, Paula; Zwoliński, Jacek; Chmielewska-Badora, Jolanta; Adamczuk, Piotr; Krasowska, Ewelina; Zagórski, Jerzy; Oniszczuk, Anna; Piątek, Jacek; Silny, Wojciech

2014-01-01

Obesity is a civilization disease and the proportion of people suffering from it continues to grow, especially in the developed countries. Number of obese people in Europe has increased threefold over the last 20 years. The paradox of obesity and poverty relationship is observed especially in the developed and developing countries. In developing countries, along with economic development and income growth, the number of people with overweight and obesity is increasing. This paradox has a relationship with both the easy availability and low cost of highly processed foods containing 'empty calories' and no nutritional value. To date, this paradox has been described in the United States and the United Kingdom, although many European countries are also experiencing high percentages of obese people. Among the reasons for the growing obesity in the population of poor people are: higher unemployment, lower education level, and irregular meals. Another cause of obesity is low physical activity, which among the poor is associated with a lack of money for sports equipment. Due to the large rate of deaths caused by diseases directly linked to obesity, the governments of many countries implement prevention programmes of overweight and obesity. These programmes are based primarily on educating the public about a healthy lifestyle based on healthy eating, daily physical activity and avoiding alcohol and cigarettes.

First status report on regional ground-water flow modeling for the Paradox Basin, Utah

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrews, R.W.

1984-05-01

Regional ground-water flow within the principal hydrogeologic units of the Paradox Basin is evaluated by developing a conceptual model of the flow regime in the shallow aquifers and the deep-basin brine aquifers and testing these models using a three-dimensional, finite-difference flow code. Semiquantitative sensitivity analysis (a limited parametric study) is conducted to define the system response to changes in hydrologic properties or boundary conditions. A direct method for sensitivity analysis using an adjoint form of the flow equation is applied to the conceptualized flow regime in the Leadville limestone aquifer. All steps leading to the final results and conclusions aremore » incorporated in this report. The available data utilized in this study is summarized. The specific conceptual models, defining the areal and vertical averaging of litho-logic units, aquifer properties, fluid properties, and hydrologic boundary conditions, are described in detail. Two models were evaluated in this study: a regional model encompassing the hydrogeologic units above and below the Paradox Formation/Hermosa Group and a refined scale model which incorporated only the post Paradox strata. The results are delineated by the simulated potentiometric surfaces and tables summarizing areal and vertical boundary fluxes, Darcy velocities at specific points, and ground-water travel paths. Results from the adjoint sensitivity analysis include importance functions and sensitivity coefficients, using heads or the average Darcy velocities to represent system response. The reported work is the first stage of an ongoing evaluation of the Gibson Dome area within the Paradox Basin as a potential repository for high-level radioactive wastes.« less

Experimental joint weak measurement on a photon pair as a probe of Hardy's paradox.

PubMed

Lundeen, J S; Steinberg, A M

2009-01-16

It has been proposed that the ability to perform joint weak measurements on postselected systems would allow us to study quantum paradoxes. These measurements can investigate the history of those particles that contribute to the paradoxical outcome. Here we experimentally perform weak measurements of joint (i.e., nonlocal) observables. In an implementation of Hardy's paradox, we weakly measure the locations of two photons, the subject of the conflicting statements behind the paradox. Remarkably, the resulting weak probabilities verify all of these statements but, at the same time, resolve the paradox.

The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression

PubMed Central

Brown, Joel S.; Cunningham, Jessica J.; Gatenby, Robert A.

2015-01-01

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed—a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler–Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the ‘cost’ (decreased fecundity) of suppression verses the ‘cost’ of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. PMID:26056365

DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates tumor cells response to platinum with corresponding alteration in the expression of BRCA1

PubMed Central

2012-01-01

Background Overcoming platinum resistance is a major obstacle in the treatment of Epithelial Ovarian Cancer (EOC). In our previous work Decoy Receptor 3 (DcR3) was found to be related to platinum resistance. The major objective of this work was to define the cellular interaction of DcR3 with EOC and to explore its effects on platinum responsiveness. Methods We studied cell lines and primary cultures for the expression of and the cells ability to bind DcR3. Cells were cultured with DcR3 and then exposed to platinum. Cell viability was determined by MTT assay. Finally, the cells molecular response to DcR3 was studied using real time RT-PCR based differential expression arrays, standard RT-PCR, and Western blot. Results High DcR3 in the peritoneal cavity of women with EOC is associated with significantly shorter time to first recurrence after platinum based therapy (p = 0.02). None-malignant cells contribute DcR3 in the peritoneal cavity. The cell lines studied do not secrete DcR3; however they all bind exogenous DcR3 to their surface implying that they can be effected by DcR3 from other sources. DcR3s protein binding partners are minimally expressed or negative, however, all cells expressed the DcR3 binding Heparan Sulfate Proteoglycans (HSPGs) Syndecans-2, and CD44v3. DcR3 binding was inhibited by heparin and heparinase. After DcR3 exposure both SKOV-3 and OVCAR-3 became more resistant to platinum with 15% more cells surviving at high doses. On the contrary CaOV3 became more sensitive to platinum with 20–25% more cell death. PCR array analysis showed increase expression of BRCA1 mRNA in SKOV-3 and OVCAR-3 and decreased BRCA1 expression in CaOV-3 after exposure to DcR3. This was confirmed by gene specific real time PCR and Western blot analysis. Conclusions Non-malignant cells contribute to the high levels of DcR3 in ovarian cancer. DcR3 binds readily to EOC cells via HSPGs and alter their responsiveness to platinum chemotherapy. The paradoxical responses seen were related to the expression pattern of HSPGs available on the cells surface to interact with. Although the mechanism behind this is not completely known alterations in DNA repair pathways including the expression of BRCA1 appear to be involved. PMID:22583667

The motivation paradox: higher psychosocial problem levels in severely mentally ill patients are associated with less motivation for treatment.

PubMed

Mulder, Cornelis L; Jochems, E; Kortrijk, H E

2014-04-01

Lack of motivation for treatment makes a subgroup of patients with severe mental illness (SMI) difficult to engage in psychiatric treatment. Such difficult-to-engage patients may also be the most in need of treatment. We hypothesized that the level of psychosocial problems would be inversely related to motivation for treatment. Cross-sectional study in two independent samples. The first sample (n = 294) included SMI patients who participated in a randomized controlled trial and were assessed using the Health of the Nation Outcome Scales (HoNOS) and self-rated and clinician-rated motivation-for-treatment scales. The second sample (n = 1,170) included SMI patients who were treated in Assertive Outreach Teams and were routinely assessed with the HoNOS and a motivation-for-treatment scale. In both samples, patients also self-rated their quality of life. In both samples, patients with HoNOS scores of 16 and higher had lower motivation scores on all motivation scales than patients with lower HoNOS scores, and also a lower quality of life. A motivation paradox seems inherent to this association between higher psychosocial problems levels, less motivation for treatment, and lower quality of life. Such a paradox has clinical relevance, as it may provide an ethical basis for outreach services which aim to engage marginally motivated SMI patients with severe psychosocial problems into mental health care.

Interdependent genotoxic mechanisms of monomethylarsonous acid: Role of ROS-induced DNA damage and poly(ADP-ribose) polymerase-1 inhibition in the malignant transformation of urothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wnek, Shawn M.; Kuhlman, Christopher L.; Camarillo, Jeannie M.

2011-11-15

Exposure of human bladder urothelial cells (UROtsa) to 50 nM of the arsenic metabolite, monomethylarsonous acid (MMA{sup III}), for 12 weeks results in irreversible malignant transformation. The ability of continuous, low-level MMA{sup III} exposure to cause an increase in genotoxic potential by inhibiting repair processes necessary to maintain genomic stability is unknown. Following genomic insult within cellular systems poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger protein, is rapidly activated and recruited to sites of DNA strand breaks. When UROtsa cells are continuously exposed to 50 nM MMA{sup III}, PARP-1 activity does not increase despite the increase in MMA{sup III}-induced DNA single-strandmore » breaks through 12 weeks of exposure. When UROtsa cells are removed from continuous MMA{sup III} exposure (2 weeks), PARP-1 activity increases coinciding with a subsequent decrease in DNA damage levels. Paradoxically, PARP-1 mRNA expression and protein levels are elevated in the presence of continuous MMA{sup III} indicating a possible mechanism to compensate for the inhibition of PARP-1 activity in the presence of MMA{sup III}. The zinc finger domains of PARP-1 contain vicinal sulfhydryl groups which may act as a potential site for MMA{sup III} to bind, displace zinc ion, and render PARP-1 inactive. Mass spectrometry analysis demonstrates the ability of MMA{sup III} to bind a synthetic peptide representing the zinc-finger domain of PARP-1, and displace zinc from the peptide in a dose-dependent manner. In the presence of continuous MMA{sup III} exposure, continuous 4-week zinc supplementation restored PARP-1 activity levels and reduced the genotoxicity associated with MMA{sup III}. Zinc supplementation did not produce an overall increase in PARP-1 protein levels, decrease the levels of MMA{sup III}-induced reactive oxygen species, or alter Cu-Zn superoxide dismutase levels. Overall, these results present two potential interdependent mechanisms in which MMA{sup III} may increase the susceptibility of UROtsa cells to genotoxic insult and/or malignant transformation: elevated levels of MMA{sup III}-induced DNA damage through the production of reactive oxygen species, and the direct MMA{sup III}-induced inhibition of PARP-1.« less

Evaluating paradox walnut rootstocks for resistance to Armillaria root disease

USDA-ARS?s Scientific Manuscript database

The most common Juglans regia (English walnut) rootstock in California is Paradox, a hybrid between J. hindsii (Northern California black walnut) and J. regia. Unfortuntely, Paradox rootstock is highly susceptible to Armillaria root disease. The relative resistance of new clonal, Paradox rootstock...

[The paradoxical effect of persuasive communication in health education sessions].

PubMed

Piperini, Marie-Christine

2012-01-01

The purpose of this study was to examine the communication dynamics leading to the adoption of new attitudes and cognitions in health education sessions. We examined the verbal interactions at work in persuasive communication in 16 health education sessions. The study found that the medical expertise of the educator and the initial level of commitment of the participants had a positive effect on adherence to recommendations. However, persuasive communication in health education sessions appears to involve a paradoxical process in which criticism of the message can go hand in hand with the expression of an intention to implement new risk-reducing behaviors.

Revisiting Hardy's paradox: counterfactual statements, real measurements, entanglement and weak values

NASA Astrophysics Data System (ADS)

Aharonov, Yakir; Botero, Alonso; Popescu, Sandu; Reznik, Benni; Tollaksen, Jeff

2002-08-01

Hardy's paradox is revisited. Usually the paradox is dismissed on grounds of counterfactuality, i.e., because the paradoxical effects appear only when one considers results of experiments which do not actually take place. We suggest a new set of measurements in connection with Hardy's scheme, and show that when they are actually performed, they yield strange and surprising outcomes. More generally, we claim that counterfactual paradoxes point to a deeper structure inherent to quantum mechanics.

Habituated Reason: Aristotle and the "Paradox of Moral Education"

ERIC Educational Resources Information Center

Kristjansson, Kristjan

2006-01-01

R.S. Peters coined the term "paradox of moral education". In this article, the author identifies two subordinate paradoxes: how habituated reason is psychologically possible and how heteronomously formed autonomy is morally/politically possible and justifiable. He sketches possible Aristotelian solutions of those paradoxes and argues that for…

Serum Amyloid A Production Is Triggered by Sleep Deprivation in Mice and Humans: Is That the Link between Sleep Loss and Associated Comorbidities?

PubMed Central

de Oliveira, Edson M.; Visniauskas, Bruna; Tufik, Sergio; Andersen, Monica L.; Chagas, Jair R.; Campa, Ana

2017-01-01

Serum amyloid A (SAA) was recently associated with metabolic endotoxemia, obesity and insulin resistance. Concurrently, insufficient sleep adversely affects metabolic health and is an independent predisposing factor for obesity and insulin resistance. In this study we investigated whether sleep loss modulates SAA production. The serum SAA concentration increased in C57BL/6 mice subjected to sleep restriction (SR) for 15 days or to paradoxical sleep deprivation (PSD) for 72 h. Sleep restriction also induced the upregulation of Saa1.1/Saa2.1 mRNA levels in the liver and Saa3 mRNA levels in adipose tissue. SAA levels returned to the basal range after 24 h in paradoxical sleep rebound (PSR). Metabolic endotoxemia was also a finding in SR. Increased plasma levels of SAA were also observed in healthy human volunteers subjected to two nights of total sleep deprivation (Total SD), returning to basal levels after one night of recovery. The observed increase in SAA levels may be part of the initial biochemical alterations caused by sleep deprivation, with potential to drive deleterious conditions such as metabolic endotoxemia and weight gain. PMID:28335560

A novel biological 'twin-father' temporal paradox of General Relativity in a Gödel universe - Where reproductive biology meets theoretical physics.

PubMed

Ashrafian, Hutan

2018-03-01

Several temporal paradoxes exist in physics. These include General Relativity's grandfather and ontological paradoxes and Special Relativity's Langevin-Einstein twin-paradox. General relativity paradoxes can exist due to a Gödel universe that follows Gödel's closed timelike curves solution to Einstein's field equations. A novel biological temporal paradox of General Relativity is proposed based on reproductive biology's phenomenon of heteropaternal fecundation. Herein, dizygotic twins from two different fathers are the result of concomitant fertilization during one menstrual cycle. In this case an Oedipus-like individual exposed to a Gödel closed timelike curve would sire a child during his maternal fertilization cycle. As a consequence of heteropaternal superfecundation, he would father his own dizygotic twin and would therefore generate a new class of autofraternal superfecundation, and by doing so creating a 'twin-father' temporal paradox. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multisetting Greenberger-Horne-Zeilinger paradoxes

NASA Astrophysics Data System (ADS)

Tang, Weidong; Yu, Sixia; Oh, C. H.

2017-01-01

The Greenberger-Horne-Zeilinger (GHZ) paradox provides an all-versus-nothing test for the quantum nonlocality. In most of the GHZ paradoxes known so far each observer is allowed to measure only two alternative observables. Here we present a general construction for GHZ paradoxes in which each observer measures more than two observables given that the system is prepared in the n -qudit GHZ state. By doing so we are able to construct a multisetting GHZ paradox for the n -qubit GHZ state, with n being arbitrary, which is genuine n -partite; i.e., no GHZ paradox exists when restricted to a subset of a number of observers for a given set of Mermin observables. Our result fills up the gap of the absence of a genuine GHZ paradox for the GHZ state of an even number of qubits, especially the four-qubit GHZ state as used in GHZ's original proposal.

SOCIOECONOMIC, CULTURAL, AND BEHAVIORAL FACTORS AFFECTING HISPANIC HEALTH OUTCOMES

PubMed Central

MORALES, LEO S.; LARA, MARIELENA; KINGTON, RAYNARD S.; VALDEZ, ROBERT O.; ESCARCE, JOSÉ J.

2006-01-01

Evidence suggests that social and economic factors are important determinants of health. Yet, despite higher poverty rates, less education, and worse access to health care, health outcomes of many Hispanics living in the United States today are equal to, or better than, those of non-Hispanic whites. This paradox is described in the literature as the epidemiological paradox or Hispanic health paradox. In this paper, the authors selectively review data and research supporting the existence of the epidemiological paradox. They find substantial support for the existence of the epidemiological paradox, particularly among Mexican Americans. Census undercounts of Hispanics, misclassification of Hispanic deaths, and emigration of Hispanics do not fully account for the epidemiological paradox. Identifying protective factors underlying the epidemiological paradox, while improving access to care and the economic conditions among Hispanics, are important research and policy implications of this review. PMID:12407964

How Managers Use the Stockdale Paradox to Balance "the Now and the Next"

ERIC Educational Resources Information Center

Von Bergen, C. W.; Bressler, Martin S.

2017-01-01

Recent discussions of leadership paradoxes have suggested that managers who can hold seemingly opposed, yet interrelated perspectives, are more adaptive and effective. One such paradox that has received relatively little attention is the "Stockdale Paradox," named after Admiral James Stockdale, an American naval officer who was held…

Differences in neurohormonal activity partially explain the obesity paradox in patients with heart failure: The role of sympathetic activation.

PubMed

Farré, Núria; Aranyó, Júlia; Enjuanes, Cristina; Verdú-Rotellar, José María; Ruiz, Sonia; Gonzalez-Robledo, Gina; Meroño, Oona; de Ramon, Marta; Moliner, Pedro; Bruguera, Jordi; Comin-Colet, Josep

2015-02-15

Obese patients with chronic Heart Failure (HF) have better outcome than their lean counterparts, although little is known about the pathophysiology of this obesity paradox. Our aim was to evaluate the hypothesis that patients with chronic HF and obesity (defined as body mass index (BMI)≥30kg/m(2)), may have an attenuated neurohormonal activation in comparison with non-obese patients. The present study is the post-hoc analysis of a cohort of 742 chronic HF patients from a single-center study evaluating sympathetic activation by measuring baseline levels of norepinephrine (NE). Obesity was present in 33% of patients. Higher BMI and obesity were significantly associated with lower NE levels in multivariable linear regression models adjusted for covariates (p<0.001). Addition to NE in multivariate Cox proportional hazard models attenuated the prognostic impact of BMI in terms of outcomes. Finally, when we explored the prognosis impact of raised NE levels (>70th percentile) carrying out a separate analysis in obese and non-obese patients we found that in both groups NE remained a significant independent predictor of poorer outcomes, despite the lower NE levels in patients with chronic HF and obesity: all-cause mortality hazard ratio=2.37 (95% confidence interval, 1.14-4.94) and hazard ratio=1.59 (95% confidence interval, 1.05-2.4) in obese and non-obese respectively; and cardiovascular mortality hazard ratio=3.08 (95% confidence interval, 1.05-9.01) in obese patients and hazard ratio=2.08 (95% confidence interval, 1.42-3.05) in non-obese patients. Patients with chronic HF and obesity have significantly lower sympathetic activation. This finding may partially explain the obesity paradox described in chronic HF patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Paradoxical sleep deprivation in rats causes a selective reduction in the expression of type-2 metabotropic glutamate receptors in the hippocampus.

PubMed

Panaccione, Isabella; Iacovelli, Luisa; di Nuzzo, Luigi; Nardecchia, Francesca; Mauro, Gianluca; Janiri, Delfina; De Blasi, Antonio; Sani, Gabriele; Nicoletti, Ferdinando; Orlando, Rosamaria

2017-03-01

Paradoxical sleep deprivation in rats is considered as an experimental animal model of mania endowed with face, construct, and pharmacological validity. We induced paradoxical sleep deprivation by placing rats onto a small platform surrounded by water. This procedure caused the animal to fall in the water at the onset of REM phase of sleep. Control rats were either placed onto a larger platform (which allowed them to sleep) or maintained in their home cage. Sleep deprived rats showed a substantial reduction in type-2 metabotropic glutamate (mGlu2) receptors mRNA and protein levels in the hippocampus, but not in the prefrontal cortex or corpus striatum, as compared to both groups of control rats. No changes in the expression of mGlu3 receptor mRNA levels or mGlu1α and mGlu5 receptor protein levels were found with exception of an increase in mGlu1α receptor levels in the striatum of SD rats. Moving from these findings we treated SD and control rats with the selective mGlu2 receptor enhancer, BINA (30mg/kg, i.p.). SD rats were also treated with sodium valproate (300mg/kg, i.p.) as an active comparator. Both BINA and sodium valproate were effective in reversing the manic-like phenotype evaluated in an open field arena in SD rats. BINA treatment had no effect on motor activity in control rats, suggesting that our findings were not biased by a non-specific motor-lowering activity of BINA. These findings suggest that changes in the expression of mGlu2 receptors may be associated with the enhanced motor activity observed with mania. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ciguatera poisoning.

PubMed

Achaibar, Kira C; Moore, Simon; Bain, Peter G

2007-10-01

Ciguatera is a form of poisoning that occurs after eating tropical and subtropical ciguatoxic fish. The ciguatoxins are a family of heat stable, lipid soluble cyclic polyether compounds that bind to and open voltage-sensitive Na(+) channels at resting membrane potential, resulting in neural hyperexcitability, as well as swelling of the nodes of Ranvier. The authors describe a 45-year-old man who developed acute gastrointestinal symptoms in Antigua soon after eating red snapper and grouper, potentially "ciguatoxic fish". This was followed by neurological symptoms 24-48 hours later, including temperature reversal (paradoxical dysaesthesia), intense pruritus and increased nociception as a result of a small fibre peripheral neuropathy. The patient's symptoms and small fibre neuropathy improved over a period of 10 months.

Stimulus-Dependent, Promoter-Specific Binding of Transcription Factor WRKY1 to Its Native Promoter and the Defense-Related Gene PcPR1-1 in ParsleyW⃞

PubMed Central

Turck, Franziska; Zhou, Aifen; Somssich, Imre E.

2004-01-01

WRKY transcription factors form a large family that plays a role in plant responses to biotic stress and during senescence. Defining in vivo relevant WRKY/promoter relationships has been hampered by the factors' indiscriminate binding to known W box DNA elements and their possible genetic redundance. Employing chromatin immunoprecipitations (ChIP) of cultured cells, we show that parsley (Petroselinum crispum) WRKY1 protein binds to the W boxes of its native promoter as well as to that of PcWRKY3 and the defense-related PR10-class marker gene Pathogenesis-Related1-1 (PcPR1-1). Although present at low concentrations in resting cells, WRKY1 does not appear to play a role in the immediate early gene response upon elicitation because it does not bind to the promoter at this time. Paradoxically, in vivo binding at the PcWRKY1 promoter correlates more with downregulation of gene expression, whereas previous overexpression studies suggested an activating function of WRKY1 on PcWRKY1 expression. By contrast, PcPR1-1 expression remains strong when its promoter is occupied in vivo by WRKY1. Unexpectedly, ChIP revealed that W boxes at promoter sites are constitutively occupied by other WRKY transcription factors, indicating that site recruitment does not seem to play a major role in their regulation. Rather, WRKY proteins very likely act in a network of mutually competing participants with temporal displacement occurring at defined preoccupied sites by other family members in a stimulus-dependent manner. PMID:15367720

The paradoxical moon illusions.

PubMed

Gilinsky, A S

1980-02-01

An adaptation theory of visual space is developed and applied to the data of a variety of studies of visual space perception. By distinguishing between the perceived distance of an object and that of the background or sky, the theory resolves the paradox of the moon illusions and relates both perceived size and perceived distance of the moon to the absolute level of spatial adaptation. The theory assumes that visual space expands or contracts in adjustment to changes in the sensory indicators of depth and provides a measure, A, of this adaptation-level. Changes in A have two effects--one on perceived size, one on perceived distance. Since A varies systematically as a function of angle of regard, availability of cues, and the total space-value, A is a measure of the moon illusions, and a practical index of individual differences by pilots and astronauts in the perception of the size and distance of objects on the ground and in the air.

MUCESS-Supported Ozone Studies in Upstate New York and along the Texas Gulf Coast

NASA Astrophysics Data System (ADS)

Hromis, A.; Balimuttajjo, M.; Johnson, A.; Wright, J. M.; Idowu, A.; Vieyra, D.; Musselwhite, D.; Morris, P. A.

2010-12-01

The Minority University Consortium for Earth and Space Sciences (MUCESS) supports yearly atmospheric science workshops at their respective institutions. The NSF funded program has enabled Universities and colleges that are part of MUCESS, which include Medgar Evers College, City University of NY, University of Houston-Downtown and South Carolina State University, to develop and support atmospheric studies. The goal of the annual workshops is to instruct the students on the basics of atmospheric science and provide them with hands-on experience for preparing and calibrating the instruments for measuring atmospheric parameters. The instruments are subsequently attached to weather balloons. The data is obtained with an ENSCI ECC ozonesonde, which measures ozone concentrations to parts per billion, and an iMET radiosonde, which records temperature, pressure, relative humidity, and GPS altitude and position. In March 2010, Medgar Evers hosted the workshop in Paradox, NY. Students and faculty from the three institutions attended the 3 day workshop. Subsequent to the annual workshop students from the University of Houston-Downtown (UHD) launched a series of four Sunday launches during the summer from the campus. The data from both the workshop and UHD launches was subsequently analyzed to compare ozone profiles within the troposphere and stratosphere. Comparing rural (Paradox, NY) and urban ozone profiles (Houston, Tx) provides an invaluable experience. An excellent example is the March Paradox temperature profiles as the data indicates a mid-tropospheric temperature inversion. Coincident with this inversion, there is a significant rise in ozone concentrations, the source of which is likely of non-local provenance. In contrast, the Houston summer data indicates a different story as ground level ozone is produced by industrial and transportation-related ozone sources levels which vary. Weekend ground level ozone levels on Sunday are usually relatively low because of decreased traffic, but with the raise in altitude, higher levels may be recorded that represent weekday levels.

Central Ghrelin Resistance Permits the Overconsolidation of Fear Memory.

PubMed

Harmatz, Elia S; Stone, Lauren; Lim, Seh Hong; Lee, Graham; McGrath, Anna; Gisabella, Barbara; Peng, Xiaoyu; Kosoy, Eliza; Yao, Junmei; Liu, Elizabeth; Machado, Nuno J; Weiner, Veronica S; Slocum, Warren; Cunha, Rodrigo A; Goosens, Ki A

2017-06-15

There are many contradictory findings about the role of the hormone ghrelin in aversive processing, with studies suggesting that ghrelin signaling can both inhibit and enhance aversion. Here, we characterize and reconcile the paradoxical role of ghrelin in the acquisition of fearful memories. We used enzyme-linked immunosorbent assay to measure endogenous acyl-ghrelin and corticosterone at time points surrounding auditory fear learning. We used pharmacological (systemic and intra-amygdala) manipulations of ghrelin signaling and examined several aversive and appetitive behaviors. We also used biotin-labeled ghrelin to visualize ghrelin binding sites in coronal brain sections of amygdala. All work was performed in rats. In unstressed rodents, endogenous peripheral acyl-ghrelin robustly inhibits fear memory consolidation through actions in the amygdala and accounts for virtually all interindividual variability in long-term fear memory strength. Higher levels of endogenous ghrelin after fear learning were associated with weaker long-term fear memories, and pharmacological agonism of the ghrelin receptor during the memory consolidation period reduced fear memory strength. These fear-inhibitory effects cannot be explained by changes in appetitive behavior. In contrast, we show that chronic stress, which increases both circulating endogenous acyl-ghrelin and fear memory formation, promotes profound loss of ghrelin binding sites in the amygdala and behavioral insensitivity to ghrelin receptor agonism. These studies provide a new link between stress, a novel type of metabolic resistance, and vulnerability to excessive fear memory formation and reveal that ghrelin can regulate negative emotionality in unstressed animals without altering appetite. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Fiber size, type, and myosin heavy chain content in rhesus hindlimb muscles after 2 weeks at 2 G

NASA Technical Reports Server (NTRS)

Tavakol, Morteza; Roy, Roland R.; Kim, Jung A.; Zhong, Hui; Hodgson, John A.; Hoban-Higgins, Tana M.; Fuller, Charles A.; Edgerton, V. Reggie

2002-01-01

BACKGROUND: Fiber atrophy and an increase in the percentage of fast fibers have been observed in Rhesus leg muscles after spaceflight. Hypothesis: Hypergravity will result in muscle fiber hypertrophy and an increase in the percentage of slow fibers. METHODS: Open muscle biopsies were obtained from Rhesus soleus, medial gastrocnemius (MG), and tibialis anterior (TA) muscles before and after 14 d of centrifugation (2 G) and in time-matched controls. Cage activity levels were measured by telemetry. RESULTS: Based on monoclonal antibody binding for myosin heavy chains (MHC), the fastest region of soleus contained a higher proportion of type I+II (27 vs. 13%) and had a tendency for a lower proportion of type I (38 vs. 61%, p = 0.10) fibers after than before centrifugation. There was a higher proportion of type I+II fibers in post- vs. pre-2 G (10 vs. 0.6%) MG biopsies. Fiber type distribution and MHC composition were unaffected in the TA. Overall, mean fiber sizes were unaffected by centrifugation. Average cage activity levels were 36% lower during than before 2 G. CONCLUSIONS: Our hypothesis was rejected. The changes in the proportion of fibers expressing type I MHC are the reverse of that expected with chronic loading of extensors and, paradoxically, are similar to changes observed with chronic unloading, such as occurs during spaceflight, in this primate model. The data are consistent with the observed decrease in total daily activity levels.

The paradox of high apolipoprotein A-I levels independently predicting incident type-2 diabetes among Turks.

PubMed

Onat, A; Hergenç, G; Bulur, S; Uğur, M; Küçükdurmaz, Z; Can, G

2010-06-25

Predictive value of apolipoprotein (apo) A-I for incident hypertension, metabolic syndrome (MetS), type 2 diabetes (DM) and coronary heart disease (CHD) needs further exploration. A representative sample of Turkish adults was studied with this purpose prospectively. Sex-specific apoA-I tertiles were examined regarding cardiometabolic risk. A total of 1044 men and 1067 women (aged 49+/-12 years at baseline) were followed up over 7.4 years. High serum apoA-I levels were significantly associated in multivariable analysis with female sex, aging, alcohol intake, (inversely) cigarette smoking and, in women, with systolic blood pressure. Risk of diabetes was predicted in logistic regression in both genders by top versus bottom apoA-I tertile (RR 1.98; [95%CI 1.31; 3.0]), additive to age, body mass index (BMI), C-reactive protein (CRP), HDL-cholesterol and lipid lowering drugs. By adding sex hormone-binding globulin to the model in a subset of the sample, the association between high apoA-I and incident diabetes was attenuated only in women. ApoA-I tertiles tended to be positively associated also with hypertension and CHD only in women but this did not reach significance. High compared with low serum apoA-I levels nearly double the risk for incident diabetes, additively to age, BMI, CRP, HDL-cholesterol among Turks. Systemic inflammation concomitant with prevailing MetS might turn apoA-I into proinflammatory particles. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

[Once again about "Gregg paradox" and its solution].

PubMed

Mavrodiev, E V

2002-01-01

"Gregg paradox" means that monotypical groups containing the same species (or groups of species) will be equal each other although systematics considers them as different taxa. Thus if the order of placental mammalia Tubilidentata includes one species aardvark Orycteropus after, the order itself, its single family Orycteropodiaceae, single genus of the family Orycteropus and the single species Orycteropus after can be considered as equal to each other. To solve this disagreement the author asserts that taxa of any level can be regarded as an individual according to the taxa of higher rank. Possibility of such interpretation was already suggested by Georg Cantor (1985). He supposed that a set (class) can be regarded as unity by itself. In this case connections between taxa of different levels can be realized by Peano ratio of intrasitive conformities. In this model a genus will consist of species but not individuals, a type--of classes, etc. Thus, if a taxon x as an individual is an element of taxon y, and taxon y as an individual is an element of taxon z, then z according to x will be not only logical class, but class of classes and, hence we could not consider x as an element of z, because the latter consists of indecomposable individual-class y or some similar classes. In this situation "Gregg paradox" does not arise.

The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression.

PubMed

Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A

2015-07-19

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed--a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler-Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the 'cost' (decreased fecundity) of suppression verses the 'cost' of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Engineering cofactor and ligand binding in an artificial neuroglobin

NASA Astrophysics Data System (ADS)

Zhang, Lei

HP-7 is one artificial mutated oxygen transport protein, which operates via a mechanism akin to human neuroglobin and cytoglobin. This protein destabilizes one of two heme-ligating histidine residues by coupling histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Replacement of these glutamate residues with alanine, which has a neutral hydrophobicity, slows gaseous ligand binding 22-fold, increases the affinity of the distal histidine ligand by a factor of thirteen, and decreases the binding affinity of carbon monoxide, a nonreactive oxygen analogue, three-fold. Paradoxically, it also decreases heme binding affinity by a factor of three in the reduced state and six in the oxidized state. Application of a two-state binding model, in which an initial pentacoordinate binding event is followed by a protein conformational change to hexacoordinate, provides insight into the mechanism of this seemingly counterintuitive result: the initial pentacoordinate encounter complex is significantly destabilized by the loss of the glutamate side chains, and the increased affinity for the distal histidine only partially compensates. These results point to the importance of considering each oxidation and conformational state in the design of functional artificial proteins. We have also examined the effects these mutations have on function. The K d of the nonnreactive oxygen analogue carbon monoxide (CO) is only decreased three-fold, despite the large increase in distal histidine affinity engendered by the 22-fold decrease in the histidine ligand off-rate. This is a result of the four-fold increase in affinity for CO binding to the pentacoordinate state. Oxygen binds to HP7 with a Kd of 117 µM, while the mutant rapidly oxidizes when exposed to oxygen. EPR analysis of both ferric hemoproteins demonstrates that the mutation increases disorder at the heme binding site. NMR-detected deuterium exchange demonstrates that the mutation causes a large increase in water penetration into the protein core. The inability of the mutant protein may thus either be due to increased water penetration, the large decrease in binding rate caused by the increase in distal histidine affinity, or a combination of the two factors.

Can economic deprivation protect health? Paradoxical multilevel effects of poverty on Hispanic children's wheezing.

PubMed

Collins, Timothy W; Kim, Young-an; Grineski, Sara E; Clark-Reyna, Stephanie

2014-08-06

Prior research suggests that economic deprivation has a generally negative influence on residents' health. We employ hierarchical logistic regression modeling to test if economic deprivation presents respiratory health risks or benefits to Hispanic children living in the City of El Paso (Texas, USA) at neighborhood- and individual-levels, and whether individual-level health effects of economic deprivation vary based on neighborhood-level economic deprivation. Data come from the US Census Bureau and a population-based survey of El Paso schoolchildren. The dependent variable is children's current wheezing, an established respiratory morbidity measure, which is appropriate for use with economically-deprived children with an increased likelihood of not receiving a doctor's asthma diagnosis. Results reveal that economic deprivation (measured based on poverty status) at both neighborhood- and individual-levels is associated with reduced odds of wheezing for Hispanic children. A sensitivity analysis revealed similar significant effects of individual- and neighborhood-level poverty on the odds of doctor-diagnosed asthma. Neighborhood-level poverty did not significantly modify the observed association between individual-level poverty and Hispanic children's wheezing; however, greater neighborhood poverty tends to be more protective for poor (as opposed to non-poor) Hispanic children. These findings support a novel, multilevel understanding of seemingly paradoxical effects of economic deprivation on Hispanic health.

Can Economic Deprivation Protect Health? Paradoxical Multilevel Effects of Poverty on Hispanic Children’s Wheezing

PubMed Central

Collins, Timothy W.; Kim, Young-an; Grineski, Sara E.; Clark-Reyna, Stephanie

2014-01-01

Prior research suggests that economic deprivation has a generally negative influence on residents’ health. We employ hierarchical logistic regression modeling to test if economic deprivation presents respiratory health risks or benefits to Hispanic children living in the City of El Paso (Texas, USA) at neighborhood- and individual-levels, and whether individual-level health effects of economic deprivation vary based on neighborhood-level economic deprivation. Data come from the US Census Bureau and a population-based survey of El Paso schoolchildren. The dependent variable is children’s current wheezing, an established respiratory morbidity measure, which is appropriate for use with economically-deprived children with an increased likelihood of not receiving a doctor’s asthma diagnosis. Results reveal that economic deprivation (measured based on poverty status) at both neighborhood- and individual-levels is associated with reduced odds of wheezing for Hispanic children. A sensitivity analysis revealed similar significant effects of individual- and neighborhood-level poverty on the odds of doctor-diagnosed asthma. Neighborhood-level poverty did not significantly modify the observed association between individual-level poverty and Hispanic children’s wheezing; however, greater neighborhood poverty tends to be more protective for poor (as opposed to non-poor) Hispanic children. These findings support a novel, multilevel understanding of seemingly paradoxical effects of economic deprivation on Hispanic health. PMID:25101769

Multicultural adolescents between tradition and postmodernity: Dialogical Self Theory and the paradox of localization and globalization.

PubMed

van Meijl, Toon

2012-01-01

This chapter builds on Dialogical Self Theory to investigate the identity development of adolescents growing up in multicultural societies. Their cultural identity is not only compounded by the rapid cultural changes associated with globalization, but also by the paradoxical revival of cultural traditions which the large-scale compression of time and space has incited at local levels of society. Dialogical Self Theory, which is based on the metaphor of the self as a "society of mind," helps to understand the dilemmas of tradition and postmodernity, of localization and globalization, within the self of individual youngsters. Copyright © 2012 Wiley Periodicals, Inc., A Wiley Company.

Mathematics of the Bulgarian Electoral System

NASA Astrophysics Data System (ADS)

Konstantinov, Mihail M.; Pelova, Galina B.; Boneva, Juliana K.

2009-11-01

In this paper we consider the mathematical aspects of the Bulgarian proportional electoral systems used since 1990. They are variants of a proportional system at a nationwide level with 4-percent barrier such that the party seats are personified from a number of regional party lists. This system is unique in the world electoral practice and may lead to severe inter-party distortions. These distortions although formally correct are hardly accepted by the public and by local party activists in particular. Methods to overcome these difficulties as well as the status-quo of the problem are considered. Finally new paradoxes are studied which are generalizations of the well known paradoxes for the plain proportional systems.

Paradoxical reaction to antituberculosis therapy in a patient with lupus vulgaris.

PubMed

Santesteban, R; Bonaut, B; Córdoba, A; Yanguas, I

2015-03-01

Patients receiving treatment for tuberculosis may experience an unexpected deterioration of their disease; this is known as a paradoxical reaction. We present the case of a 59-year-old man with lupus vulgaris who experienced a paradoxical deterioration of cutaneous lesions after starting antituberculosis therapy. The reaction was self-limiting; the lesions gradually improved, and the final outcome was very good. Paradoxical reactions are well-known in patients with human immunodeficiency virus (HIV) infection who start antiretroviral therapy, but they can also occur in non-HIV-infected patients with tuberculosis who start antituberculosis therapy. In the literature reviewed, paradoxical reactions involving skin lesions were described in patients with miliary tuberculosis. The case we report is the first of a paradoxical reaction in lupus vulgaris. The increasing frequency of tuberculosis in Spain could lead to a rise in the number of paradoxical reactions. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

From the BMI paradox to the obesity paradox: the obesity-mortality association in coronary heart disease.

PubMed

Antonopoulos, A S; Oikonomou, E K; Antoniades, C; Tousoulis, D

2016-10-01

Despite a strong association between body weight and mortality in the general population, clinical evidence suggests better clinical outcome of overweight or obese individuals with established coronary heart disease. This finding has been termed the 'obesity paradox', but its existence remains a point of debate, because it is mostly observed when body mass index (BMI) is used to define obesity. Inherent limitations of BMI as an index of adiposity, as well as methodological biases and the presence of confounding factors, may account for the observed findings of clinical studies. In this review, our aim is to present the data that support the presence of a BMI paradox in coronary heart disease and then explore whether next to a BMI paradox a true obesity paradox exists as well. We conclude by attempting to link the obesity paradox notion to available translational research data supporting a 'healthy', protective adipose tissue phenotype. © 2016 World Obesity. © 2016 World Obesity.

Paradoxical arthritis occurring during anti-TNF in patients with inflammatory bowel disease: histological and immunological features of a complex synovitis.

PubMed

Alivernini, Stefano; Pugliese, Daniela; Tolusso, Barbara; Bui, Laura; Petricca, Luca; Guidi, Luisa; Mirone, Luisa; Rapaccini, Gian Ludovico; Federico, Francesco; Ferraccioli, Gianfranco; Armuzzi, Alessandro; Gremese, Elisa

2018-01-01

Paradoxical arthritis under tumour necrosis factor inhibitor (TNF-i) for inflammatory bowel disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial tissue (ST) and colonic mucosa (CM) tissue in patients with IBD developing paradoxical arthritis under TNF-i. Patients with IBD without history of coexisting joint involvement who developed arthritis under TNF-i were enrolled. Each patient underwent ST biopsy and ileocolonoscopy with CM biopsies. ST and CM paired samples were stained through immunohistochemistry (IHC) for CD68, CD21, CD20, CD3 and CD117. Clinical and immunological parameters (anticitrullinated peptides antibodies (ACPA)-immunoglobulin (Ig)M/IgA rheumatoid factor (RF)) were collected. Psoriatic arthritis (PsA) and ACPA/IgM-RF/IgA-RF negative rheumatoid arthritis (RA) were enrolled as comparison. 10 patients with IBD (age 46.0±9.7 years, 13.2±9.9 years of disease duration, 2.5±1.6 years of TNF-i exposure, six with Crohn's disease and four with ulcerative colitis, respectively) were studied. At ST level, IHC revealed that patients with IBD with paradoxical arthritis showed more similar histological findings in terms of synovial CD68 + , CD21 + , CD20 + , CD3 + and CD117 + cells compared with PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing the CM specimens, patients with IBD showed the presence of CD68 + , CD3 + , CD117 + and CD20 + cells in 100%, 70%, 60% and 50% of cases, respectively, despite endoscopic remission. Finally, addition of conventional disease-modifying antirheumatic drugs and switch to ustekinumab were more effective than swapping into different TNF-i in patients with IBD with paradoxical arthritis. Patients with IBD may develop histologically proven synovitis during TNF-i, comparable to PsA. The inhibition of inflammatory pathways alternative to TNF (IL12/1L23) may be an effective therapeutic option for severe paradoxical articular manifestations.

Paradoxical arthritis occurring during anti-TNF in patients with inflammatory bowel disease: histological and immunological features of a complex synovitis

PubMed Central

Alivernini, Stefano; Pugliese, Daniela; Tolusso, Barbara; Bui, Laura; Petricca, Luca; Guidi, Luisa; Mirone, Luisa; Rapaccini, Gian Ludovico; Federico, Francesco; Ferraccioli, Gianfranco; Armuzzi, Alessandro; Gremese, Elisa

2018-01-01

Objective Paradoxical arthritis under tumour necrosis factor inhibitor (TNF-i) for inflammatory bowel disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial tissue (ST) and colonic mucosa (CM) tissue in patients with IBD developing paradoxical arthritis under TNF-i. Methods Patients with IBD without history of coexisting joint involvement who developed arthritis under TNF-i were enrolled. Each patient underwent ST biopsy and ileocolonoscopy with CM biopsies. ST and CM paired samples were stained through immunohistochemistry (IHC) for CD68, CD21, CD20, CD3 and CD117. Clinical and immunological parameters (anticitrullinated peptides antibodies (ACPA)-immunoglobulin (Ig)M/IgA rheumatoid factor (RF)) were collected. Psoriatic arthritis (PsA) and ACPA/IgM-RF/IgA-RF negative rheumatoid arthritis (RA) were enrolled as comparison. Results 10 patients with IBD (age 46.0±9.7 years, 13.2±9.9 years of disease duration, 2.5±1.6 years of TNF-i exposure, six with Crohn’s disease and four with ulcerative colitis, respectively) were studied. At ST level, IHC revealed that patients with IBD with paradoxical arthritis showed more similar histological findings in terms of synovial CD68+, CD21+, CD20+, CD3+ and CD117+ cells compared with PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing the CM specimens, patients with IBD showed the presence of CD68+, CD3+, CD117+ and CD20+ cells in 100%, 70%, 60% and 50% of cases, respectively, despite endoscopic remission. Finally, addition of conventional disease-modifying antirheumatic drugs and switch to ustekinumab were more effective than swapping into different TNF-i in patients with IBD with paradoxical arthritis. Conclusion Patients with IBD may develop histologically proven synovitis during TNF-i, comparable to PsA. The inhibition of inflammatory pathways alternative to TNF (IL12/1L23) may be an effective therapeutic option for severe paradoxical articular manifestations. PMID:29657833

Numerical and Experimental study of secondary flows in a rotating two-phase flow: the tea leaf paradox

NASA Astrophysics Data System (ADS)

Calderer, Antoni; Neal, Douglas; Prevost, Richard; Mayrhofer, Arno; Lawrenz, Alan; Foss, John; Sotiropoulos, Fotis

2015-11-01

Secondary flows in a rotating flow in a cylinder, resulting in the so called ``tea leaf paradox'', are fundamental for understanding atmospheric pressure systems, developing techniques for separating red blood cells from the plasma, and even separating coagulated trub in the beer brewing process. We seek to gain deeper insights in this phenomenon by integrating numerical simulations and experiments. We employ the Curvilinear Immersed boundary method (CURVIB) of Calderer et al. (J. Comp. Physics 2014), which is a two-phase flow solver based on the level set method, to simulate rotating free-surface flow in a cylinder partially filled with water as in the tea leave paradox flow. We first demonstrate the validity of the numerical model by simulating a cylinder with a rotating base filled with a single fluid, obtaining results in excellent agreement with available experimental data. Then, we present results for the cylinder case with free surface, investigate the complex formation of secondary flow patterns, and show comparisons with new experimental data for this flow obtained by Lavision. Computational resources were provided by the Minnesota Supercomputing Institute.

Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.

PubMed

Furuhashi, Masato; Matsumoto, Megumi; Hiramitsu, Shinya; Omori, Akina; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junnichi; Miura, Tetsuji

2016-01-01

Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2. UMIN-CTR Clinical Trial UMIN000018151.

Bistability and Biofilm Formation in Bacillus subtilis

PubMed Central

Chai, Yunrong; Chu, Frances; Kolter, Roberto; Losick, Richard

2008-01-01

Summary Biofilms of Bacillus subtilis consist of long chains of cells that are held together in bundles by an extracellular matrix of exopolysaccharide and the protein TasA. The exopolysaccharide is produced by enzymes encoded by the epsA-O operon and the gene encoding TasA is located in the yqxM-sipW-tasA operon. Both operons are under the control of the repressor SinR. Derepression is mediated by the antirepressor SinI, which binds to SinR with a 1:1 stoichiometry. Paradoxically, in medium promoting derepression of the matrix operons, the overall concentration of SinR in the culture greatly exceeded that of SinI. We show that under biofilm-promoting conditions sinI, which is under the control of the response regulator Spo0A, was expressed only in a small subpopulation of cells, whereas sinR was expressed in almost all cells. Activation of Spo0A is known to be subject to a bistable switch, and we infer that SinI reaches levels sufficient to trigger matrix production only in the subpopulation of cells in which Spo0A is active. Additionally, evidence suggests that sinI is expressed at intermediate, but not low or high, levels of Spo0A activity, which may explain why certain nutritional conditions are more effective in promoting biofilm formation than others. PMID:18047568

Generalized Hardy's Paradox

NASA Astrophysics Data System (ADS)

Jiang, Shu-Han; Xu, Zhen-Peng; Su, Hong-Yi; Pati, Arun Kumar; Chen, Jing-Ling

2018-01-01

Here, we present the most general framework for n -particle Hardy's paradoxes, which include Hardy's original one and Cereceda's extension as special cases. Remarkably, for any n ≥3 , we demonstrate that there always exist generalized paradoxes (with the success probability as high as 1 /2n -1) that are stronger than the previous ones in showing the conflict of quantum mechanics with local realism. An experimental proposal to observe the stronger paradox is also presented for the case of three qubits. Furthermore, from these paradoxes we can construct the most general Hardy's inequalities, which enable us to detect Bell's nonlocality for more quantum states.

Pennsylvanian carbonate buildups, Paradox basin: Increasing reserves in heterogeneous, shallow-shelf reservoirs

USGS Publications Warehouse

Montgomery, S.L.; Chidsey, T.C.; Eby, D.E.; Lorenz, D.M.; Culham, W.E.

1999-01-01

Productive carbonate buildups of Pennsylvanian age in the southern Paradox basin, Utah, contain up to 200 million bbl remaining oil potentially recoverable by enhanced recovery methods. These buildups comprise over 100 satellite fields to the giant Greater Aneth field, where secondary recovery operations thus far have been concentrated. Several types of satellite buildups exist and produce oil from the Desert Creek zone of the Paradox Formation. Many of the relevant fields have undergone early abandonment; wells in Desert Creek carbonate mounds commonly produce at very high initial rates (>1000 bbl/day) and then suffer precipitous declines. An important new study focused on the detailed characterization of five separate reservoirs has resulted in significant information relevant to their future redevelopment. Completed assessment of Anasazi field suggests that phylloid algal mounds, the major productive buildup type in this area, consist of ten separate lithotypes and can be described in terms of a two-level reservoir system with an underlying high-permeability mound-core interval overlain by a lower permeability but volumetrically larger supramound (mound capping) interval. Reservoir simulations and related performance predictions indicate that CO2 flooding of these reservoirs should have considerable success in recovering remaining oil reserves.Productive carbonate buildups of Pennsylvanian age in the southern Paradox basin, Utah, contain up to 200 million bbl remaining oil potentially recoverable by enhanced recovery methods. These buildups comprise over 100 satellite fields to the giant Greater Aneth field, where secondary recovery operations thus far have been concentrated. Several types of satellite buildups exist and produce oil from the Desert Creek zone of the Paradox Formation. Many of the relevant fields have undergone early abandonment; wells in Desert Creek carbonate mounds commonly produce at very high initial rates (>1000 bbl/day) and then suffer precipitous declines. An important new study focused on the detailed characterization of five separate reservoirs has resulted in significant information relevant to their future redevelopment. Completed assessment of Anasazi field suggests that phylloid algal mounds, the major productive buildup type in this area, consist of ten separate lithotypes and can be described in terms of a two-level reservoir system with an underlying high-permeability mound-core interval overlain by a lower permeability but volumetrically larger supramound (mound capping) interval. Reservoir simulations and related performance predictions indicate that CO2 flooding of these reservoirs should have considerable success in recovering remaining oil reserves.

Paradoxical aortic stenosis: A systematic review.

PubMed

Cavaca, Rita; Teixeira, Rogério; Vieira, Maria João; Gonçalves, Lino

2017-04-01

Aortic stenosis (AS) is a complex systemic valvular and vascular disease with a high prevalence in developed countries. The new entity "paradoxical low-flow, low-gradient aortic stenosis" refers to cases in which patients have severe AS based on assessment of aortic valve area (AVA) (≤1 cm 2 ) or indexed AVA (≤0.6 cm 2 /m 2 ), but paradoxically have a low mean transvalvular gradient (<40 mmHg) and a low stroke volume index (≤35 ml/m 2 ), despite preserved left ventricular ejection fraction (≥50%). A search was carried out in the PubMed database on paradoxical AS for the period 2007-2014. A total of 57 articles were included for this review. The prevalence of paradoxical AS ranged from 3% to 35% of the population with severe degenerative AS. It was more frequent in females and in older patients. Paradoxical AS was associated with characteristic left ventricular remodeling as well as an increase in systemic arterial stiffness. It was noted that there may be errors and inaccuracies in the calculation of AVA by the continuity equation, which could erroneously suggest the paradoxical phenotype. There are new diagnostic methods to facilitate the study of AS, such as aortic valve calcium score, valvuloarterial impedance and the longitudinal mechanics of the left ventricle. With regard to its natural history, it is not clear whether paradoxical AS corresponds to an advance stage of the disease or if paradoxical AS patients have a distinct phenotype with specific characteristics. Valve replacement, either surgical or percutaneous, may be indicated in patients with severe and symptomatic paradoxical AS. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Unveiling consumer's privacy paradox behaviour in an economic exchange.

PubMed

Motiwalla, Luvai F; Li, Xiao-Bai

2016-01-01

Privacy paradox is of great interest to IS researchers and firms gathering personal information. It has been studied from social, behavioural, and economic perspectives independently. However, prior research has not examined the degrees of influence these perspectives contribute to the privacy paradox problem. We combine both economic and behavioural perspectives in our study of the privacy paradox with a price valuation of personal information through an economic experiment combined with a behavioural study on privacy paradox. Our goal is to reveal more insights on the privacy paradox through economic valuation on personal information. Results indicate that general privacy concerns or individual disclosure concerns do not have a significant influence on the price valuation of personal information. Instead, prior disclosure behaviour in specific scenario, like with healthcare providers or social networks, is a better indicator of consumer price valuations.

Unveiling consumer’s privacy paradox behaviour in an economic exchange

PubMed Central

Li, Xiao-Bai

2015-01-01

Privacy paradox is of great interest to IS researchers and firms gathering personal information. It has been studied from social, behavioural, and economic perspectives independently. However, prior research has not examined the degrees of influence these perspectives contribute to the privacy paradox problem. We combine both economic and behavioural perspectives in our study of the privacy paradox with a price valuation of personal information through an economic experiment combined with a behavioural study on privacy paradox. Our goal is to reveal more insights on the privacy paradox through economic valuation on personal information. Results indicate that general privacy concerns or individual disclosure concerns do not have a significant influence on the price valuation of personal information. Instead, prior disclosure behaviour in specific scenario, like with healthcare providers or social networks, is a better indicator of consumer price valuations. PMID:27708687

The three paradoxes of patient flow: an explanatory case study.

PubMed

Kreindler, Sara A

2017-07-12

Health systems in many jurisdictions struggle to reduce Emergency Department congestion and improve patient flow across the continuum of care. Flow is often described as a systemic issue requiring a "system approach"; however, the implications of this idea remain poorly understood. Focusing on a Canadian regional health system whose flow problems have been particularly intractable, this study sought to determine what system-level flaws impede healthcare organizations from improving flow. This study drew primarily on qualitative data from in-depth interviews with 62 senior, middle and departmental managers representing the Region, its programs and sites; quantitative analysis of key flow indicators (1999-2012) and review of ~700 documents furnished important context. Examination of the interview data revealed that the most striking feature of the dataset was contradiction; accordingly, a technique of dialectical analysis was developed to examine observed contradictions at successively deeper levels. Analysis uncovered three paradoxes: "Many Small Successes and One Big Failure" (initiatives improve parts of the system but fail to fix underlying system constraints); "Your Innovation Is My Aggravation" (local innovation clashes with regional integration); and most critically, "Your Order Is My Chaos" (rules that improve service organization for my patients create obstacles for yours). This last emerges when some entities (sites/hospitals) define their patients in terms of their location in the system, while others (regional programs) define them in terms of their needs/characteristics. As accountability for improving flow was distributed among groups that thus variously defined their patients, local efforts achieved little for the overall system, and often clashed with each other. These paradoxes are indicative of a fundamental antagonism between the system's parts and the whole. An accretion of flow initiatives in all parts of the system will never add up to a system approach, and may indeed perpetuate the paradoxes. What is needed is a coherent strategy of defining patient populations by needs, analyzing their entire trajectories of care, and developing consistent processes to better meet those needs.

An Acid Hydrocarbon: A Chemical Paradox

ERIC Educational Resources Information Center

Burke, Jeffrey T.

2004-01-01

The chemical paradox of cyclopentadiene, a hydrocarbon, producing bubbles like a Bronsted acid is observed. The explanation that it is the comparative thermodynamic constancy of the fragrant cyclopentadienyl anion, which produces the powerful effect, resolves the paradox.

NR2A- and NR2B-NMDA receptors and drebrin within postsynaptic spines of the hippocampus correlate with hunger-evoked exercise.

PubMed

Chen, Yi-Wen; Actor-Engel, Hannah; Sherpa, Ang Doma; Klingensmith, Lauren; Chowdhury, Tara G; Aoki, Chiye

2017-07-01

Hunger evokes foraging. This innate response can be quantified as voluntary wheel running following food restriction (FR). Paradoxically, imposing severe FR evokes voluntary FR, as some animals choose to run rather than eat, even during limited periods of food availability. This phenomenon, called activity-based anorexia (ABA), has been used to identify brain changes associated with FR and excessive exercise (EX), two core symptoms of anorexia nervosa (AN), and to explore neurobiological bases of AN vulnerability. Previously, we showed a strong positive correlation between suppression of FR-evoked hyperactivity, i.e., ABA resilience, and levels of extra-synaptic GABA receptors in stratum radiatum (SR) of hippocampal CA1. Here, we tested for the converse: whether animals with enhanced expression of NMDA receptors (NMDARs) exhibit greater levels of FR-evoked hyperactivity, i.e., ABA vulnerability. Four groups of animals were assessed for NMDAR levels at CA1 spines: (1) ABA, in which 4 days of FR was combined with wheel access to allow voluntary EX; (2) FR only; (3) EX only; and (4) control (CON) that experienced neither EX nor FR. Electron microscopy revealed that synaptic NR2A-NMDARs and NR2B-NMDARs levels are significantly elevated, relative to CONs'. Individuals' ABA severity, based on weight loss, correlated with synaptic NR2B-NMDAR levels. ABA resilience, quantified as suppression of hyperactivity, correlated strongly with reserve pools of NR2A-NMDARs in spine cytoplasm. NR2A- and NR2B-NMDAR measurements correlated with spinous prevalence of an F-actin binding protein, drebrin, suggesting that drebrin enables insertion of NR2B-NMDAR to and retention of NR2A-NMDARs away from synaptic membranes, together influencing ABA vulnerability.

Consequences of placing an intramolecular crosslink in myosin S1

PubMed Central

Konno, Kunihiko; Ue, Kathleen; Khoroshev, Mikhail; Martinez, Hugo; Ray, Bruce; Morales, Manuel F.

2000-01-01

This paper describes the placement of a crosslinking agent (dibromobimane) between two thiols (Cys-522 and Cys-707) of a fragment, “S1,” of the motor protein, myosin. It turns out that fastening the first anchor of the crosslinker is easy and rapid, but fastening the second anchor (Cys-522) is very temperature dependent, taking 30 min at room temperature but about a week on ice. Moreover, crystallography taken at 4°C would seem to predict that the linkage is impossible, because the span of the crosslinking agent is much less than the interthiol distance. The simplest resolution of this seeming paradox is that structural fluctuations of the protein render the linkage increasingly likely as the temperature increases. Also, measurements of the affinity of MgADP for the protein, as well as the magnetic resonance of the P-atoms of the ADP once emplaced, suggest that binding the first reagent anchor to Cys-707 initiates an influence that travels to the rather distant ADP-binding site, and it is speculated what this “path of influence” might be. PMID:10677484

Resistance of Akt kinases to dephosphorylation through ATP-dependent conformational plasticity.

PubMed

Chan, Tung O; Zhang, Jin; Rodeck, Ulrich; Pascal, John M; Armen, Roger S; Spring, Maureen; Dumitru, Calin D; Myers, Valerie; Li, Xue; Cheung, Joseph Y; Feldman, Arthur M

2011-11-15

Phosphorylation of a threonine residue (T308 in Akt1) in the activation loop of Akt kinases is a prerequisite for deregulated Akt activity frequently observed in neoplasia. Akt phosphorylation in vivo is balanced by the opposite activities of kinases and phosphatases. Here we describe that targeting Akt kinase to the cell membrane markedly reduced sensitivity of phosphorylated Akt to dephosphorylation by protein phosphatase 2A. This effect was amplified by occupancy of the ATP binding pocket by either ATP or ATP-competitive inhibitors. Mutational analysis revealed that R273 in Akt1 and the corresponding R274 in Akt2 are essential for shielding T308 in the activation loop against dephosphorylation. Thus, occupancy of the nucleotide binding pocket of Akt kinases enables intramolecular interactions that restrict phosphatase access and sustain Akt phosphorylation. This mechanism provides an explanation for the "paradoxical" Akt hyperphosphorylation induced by ATP-competitive inhibitor, A-443654. The lack of phosphatase resistance further contributes insight into the mechanism by which the human Akt2 R274H missense mutation may cause autosomal-dominant diabetes mellitus.

Paradoxical roles of hydrogen in electrochemical performance of graphene: High rate capacity and atomistic origins

DOE PAGES

Ye, Jianchao C.; Ong, Mitchell T.; Heo, Tae Wook; ...

2015-11-05

Atomic hydrogen exists ubiquitously in graphene materials made by chemical methods. Yet determining the effect of hydrogen on the electrochemical performance of graphene remains a significant challenge. Here we report the experimental observations of high rate capacity in hydrogen-treated 3-dimensional (3D) graphene nanofoam electrodes for lithium ion batteries. Structural and electronic characterization suggests that defect sites and hydrogen play synergistic roles in disrupting sp 2 graphene to facilitate fast lithium transport and reversible surface binding, as evidenced by the fast charge-transfer kinetics and increased capacitive contribution in hydrogen-treated 3D graphene. In concert with experiments, multiscale calculations reveal that defect complexesmore » in graphene are prerequisite for low-temperature hydrogenation, and that the hydrogenation of defective or functionalized sites at strained domain boundaries plays a beneficial role in improving rate capacity by opening gaps to facilitate easier Li penetration. Additional reversible capacity is provided by enhanced lithium binding near hydrogen-terminated edge sites. Furthermore, these findings provide qualitative insights in helping the design of graphene-based materials for high-power electrodes.« less

Managing the Paradox of Control: The Case of Ground-Up Implementation of Active Learning in Singapore's Primary Schools

ERIC Educational Resources Information Center

Lim-Ratnam, Christina; Atencio, Matthew; Lee, Christine Kim-Eng

2016-01-01

The Singaporean education system has recently shifted emphasis from being highly centralised and standardised towards one that aims to promote innovation and autonomy at the school level. Yet, the concomitant move towards a more decentralised and flexible curriculum enacted and controlled at the local level has not been straightforward.…

Geometric description of modular and weak values in discrete quantum systems using the Majorana representation

NASA Astrophysics Data System (ADS)

Cormann, Mirko; Caudano, Yves

2017-07-01

We express modular and weak values of observables of three- and higher-level quantum systems in their polar form. The Majorana representation of N-level systems in terms of symmetric states of N  -  1 qubits provides us with a description on the Bloch sphere. With this geometric approach, we find that modular and weak values of observables of N-level quantum systems can be factored in N  -  1 contributions. Their modulus is determined by the product of N  -  1 ratios involving projection probabilities between qubits, while their argument is deduced from a sum of N  -  1 solid angles on the Bloch sphere. These theoretical results allow us to study the geometric origin of the quantum phase discontinuity around singularities of weak values in three-level systems. We also analyze the three-box paradox (Aharonov and Vaidman 1991 J. Phys. A: Math. Gen. 24 2315-28) from the point of view of a bipartite quantum system. In the Majorana representation of this paradox, an observer comes to opposite conclusions about the entanglement state of the particles that were successfully pre- and postselected.

Paradoxical physiological responses to propranolol in a Rett syndrome patient: a case report.

PubMed

Santosh, P J; Bell, L; Lievesley, K; Singh, J; Fiori, F

2016-11-29

Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT. The prototypical beta blocker propranolol has been used to manage sympathetic hyperactivity in patients with RTT. A 13 year old girl with RTT was referred to the Centre for Interventional Paediatric Psychopharmacology and Rare Diseases (CIPPRD), South London and Maudsley NHS Foundation Trust. Her clinical picture included disordered breathing with concomitant hyperventilation and apnoea, epilepsy, scoliosis, no QT prolongation (QT/QTc [372/467 ms on automated electrocardiogram [ECG], but manually calculated to be 440 ms]), no cardiac abnormalities (PR interval: 104 ms, QRS duration: 78 ms), and generalised anxiety disorder (ICD-10-CM Diagnosis Code F41.1). She was also constipated and was fed via percutaneous endoscopic gastrostomy (PEG). To manage the dysautonomia, propranolol was given (5 mg and 10 mg) and in parallel her physiological parameters, including heart rate, skin temperature and skin transpiration, were monitored continuously for 24 h as she went about her activities of daily living. Whilst her skin temperature increased and skin transpiration decreased, unexpectedly there was a significant paradoxical increase in the patient's average heart rate following propranolol treatment. Here, we present a unique case of a paradoxical increase in heart rate response following propranolol treatment for managing dysautonomia in a child with RTT. Further studies are warranted to better understand the underlying dysautonomia in patients with RTT and the impact this might have on treatment strategies in rare disorders such as RTT.

Sheet-like assemblies of spherical particles with point-symmetrical patches.

PubMed

Mani, Ethayaraja; Sanz, Eduardo; Roy, Soumyajit; Dijkstra, Marjolein; Groenewold, Jan; Kegel, Willem K

2012-04-14

We report a computational study on the spontaneous self-assembly of spherical particles into two-dimensional crystals. The experimental observation of such structures stabilized by spherical objects appeared paradoxical so far. We implement patchy interactions with the patches point-symmetrically (icosahedral and cubic) arranged on the surface of the particle. In these conditions, preference for self-assembly into sheet-like structures is observed. We explain our findings in terms of the inherent symmetry of the patches and the competition between binding energy and vibrational entropy. The simulation results explain why hollow spherical shells observed in some Keplerate-type polyoxometalates (POM) appear. Our results also provide an explanation for the experimentally observed layer-by-layer growth of apoferritin--a quasi-spherical protein.

Differential regulation by ATP versus ADP further links CaMKII aggregation to ischemic conditions

PubMed Central

Vest, Rebekah S.; O’Leary, Heather; Bayer, K. Ulrich

2009-01-01

CaMKII, a major mediator of synaptic plasticity, forms extra-synaptic clusters under ischemic conditions. This study further supports self-aggregation of CaMKII holoenzymes as the underlying mechanism. Aggregation in vitro was promoted by mimicking ischemic conditions: low pH (6.8 or less), Ca2+ (and calmodulin), and low ATP and/or high ADP concentration. Mutational analysis showed that high ATP prevented aggregation by a mechanism involving T286 auto-phosphorylation, and indicated requirement for nucleotide binding but not auto-phosphorylation also for extra-synaptic clustering within neurons. These results clarify a previously apparent paradox in the nucleotide and phosphorylation requirement of aggregation, and support a mechanism that involves inter-holoenzyme T286-region/T-site interaction. PMID:19840793

Psychological tasks associated with divorce: Eat, Pray, Love (2010), An Unmarried Woman (1978), and Kramer vs. Kramer (1979).

PubMed

Mandelbaum, Toni

2011-06-01

The dependency paradox (Feeney) states that independence actually can result from being in a nurturing relationship. Those who divorce often have the opposite notion that independence will occur without a relationship. The movies Eat, Pray, Love, An Unmarried Woman, and Kramer vs. Kramer examine divorce from different angles. The protagonists in all three movies grow through the process of divorce, each achieving a level of autonomy that seemed unattainable within their marriage. This paper aims to explore the concept of divorce in light of the dependency paradox by examining the self-differentiation achieved and the consequences of such independence for both the individual and, in Kramer vs. Kramer, for the child involved.

The paradox of cognitive flexibility in autism

PubMed Central

Geurts, Hilde M.; Corbett, Blythe; Solomon, Marjorie

2017-01-01

We present an overview of current literature addressing cognitive flexibility in autism spectrum disorders. Based on recent studies at multiple sites, using diverse methods and participants of different autism subtypes, ages and cognitive levels, no consistent evidence for cognitive flexibility deficits was found. Researchers and clinicians assume that inflexible everyday behaviors in autism are directly related to cognitive flexibility deficits as assessed by clinical and experimental measures. However, there is a large gap between the day-to-day behavioral flexibility and that measured with these cognitive flexibility tasks. To advance the field, experimental measures must evolve to reflect mechanistic models of flexibility deficits. Moreover, ecologically valid measures are required to be able to resolve the paradox between cognitive and behavioral inflexibility. PMID:19138551

Simpson's Paradox: Examples.

PubMed

Wang, Bokai; Wu, Pan; Kwan, Brian; Tu, Xin M; Feng, Changyong

2018-04-25

Simpson's paradox is very prevalent in many areas. It characterizes the inconsistency between the conditional and marginal interpretations of the data. In this paper, we illustrate through some examples how the Simpson's paradox can happen in continuous, categorical, and time-to-event data.

Epidemiology of Myocardial Infarction Caused by Presumed Paradoxical Embolism via a Patent Foramen Ovale.

PubMed

Kleber, Franz X; Hauschild, Telse; Schulz, Antonia; Winkelmann, Anne; Bruch, Leonhard

2017-09-25

Despite several negative prospective randomized trials on the efficacy of patent foramen ovale (PFO) occlusion, the discussion on indications is ongoing. Because the incidence of paradoxical coronary embolism through a PFO is unknown, we investigated the risk of paradoxical embolic myocardial infarction over a period of 13 years.Methods and Results:We conducted a retrospective and a prospective study. In the former, we searched the hospital database of a tertiary referral center for cases of acute myocardial infarction (AMI) during the past 10 years and screened them for possible paradoxical MIs. On this basis we started a prospective evaluation over 39 months in another tertiary referral center. All patients with AMI and normal coronary arteries were screened for PFO and if no other reason for the AMI could be found, the case was judged as presumed paradoxical embolism. In the retrospective analysis we found 22 cases (0.45%) of presumed paradoxical coronary artery embolism under 4,848 AMI. In the prospective study there were 11 presumed paradoxical coronary artery embolisms among 1,654 patients with AMI, representing an incidence of 0.67%. Our findings demonstrated that well below 1% of AMIs are caused by paradoxical embolism via an interatrial communication. Although this percentage appears low, it is not a negligible number of patients based on the huge number of MIs occurring in the industrialized world.

The intelligence paradox; will ET get the metabolic syndrome? Lessons from and for Earth.

PubMed

Nunn, Alistair V W; Guy, Geoffrey W; Bell, Jimmy D

2014-01-01

Mankind is facing an unprecedented health challenge in the current pandemic of obesity and diabetes. We propose that this is the inevitable (and predictable) consequence of the evolution of intelligence, which itself could be an expression of life being an information system driven by entropy. Because of its ability to make life more adaptable and robust, intelligence evolved as an efficient adaptive response to the stresses arising from an ever-changing environment. These adaptive responses are encapsulated by the epiphenomena of "hormesis", a phenomenon we believe to be central to the evolution of intelligence and essential for the maintenance of optimal physiological function and health. Thus, as intelligence evolved, it would eventually reach a cognitive level with the ability to control its environment through technology and have the ability remove all stressors. In effect, it would act to remove the very hormetic factors that had driven its evolution. Mankind may have reached this point, creating an environmental utopia that has reduced the very stimuli necessary for optimal health and the evolution of intelligence - "the intelligence paradox". One of the hallmarks of this paradox is of course the rising incidence in obesity, diabetes and the metabolic syndrome. This leads to the conclusion that wherever life evolves, here on earth or in another part of the galaxy, the "intelligence paradox" would be the inevitable side-effect of the evolution of intelligence. ET may not need to just "phone home" but may also need to "phone the local gym". This suggests another possible reason to explain Fermi's paradox; Enrico Fermi, the famous physicist, suggested in the 1950s that if extra-terrestrial intelligence was so prevalent, which was a common belief at the time, then where was it? Our suggestion is that if advanced life has got going elsewhere in our galaxy, it can't afford to explore the galaxy because it has to pay its healthcare costs.

Ca2+ paradox injury mediated through TRPC channels in mouse ventricular myocytes

PubMed Central

Kojima, Akiko; Kitagawa, Hirotoshi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Nosaka, Shuichi

2010-01-01

BACKGROUND AND PURPOSE The Ca2+ paradox is an important phenomenon associated with Ca2+ overload-mediated cellular injury in myocardium. The present study was undertaken to elucidate molecular and cellular mechanisms for the development of the Ca2+ paradox. EXPERIMENTAL APPROACH Fluorescence imaging was performed on fluo-3 loaded quiescent mouse ventricular myocytes using confocal laser scanning microscope. KEY RESULTS The Ca2+ paradox was readily evoked by restoration of the extracellular Ca2+ following 10–20 min of nominally Ca2+-free superfusion. The Ca2+ paradox was significantly reduced by blockers of transient receptor potential canonical (TRPC) channels (2-aminoethoxydiphenyl borate, Gd3+, La3+) and anti-TRPC1 antibody. The sarcoplasmic reticulum (SR) Ca2+ content, assessed by caffeine application, gradually declined during Ca2+-free superfusion, which was further accelerated by metabolic inhibition. Block of SR Ca2+ leak by tetracaine prevented Ca2+ paradox. The Na+/Ca2+ exchange (NCX) blocker KB-R7943 significantly inhibited Ca2+ paradox when applied throughout superfusion period, but had little effect when added for a period of 3 min before and during Ca2+ restoration. The SR Ca2+ content was better preserved during Ca2+ depletion by KB-R7943. Immunocytochemistry confirmed the expression of TRPC1, in addition to TRPC3 and TRPC4, in mouse ventricular myocytes. CONCLUSIONS AND IMPLICATIONS These results provide evidence that (i) the Ca2+ paradox is primarily mediated by Ca2+ entry through TRPC (probably TRPC1) channels that are presumably activated by SR Ca2+ depletion; and (ii) reverse mode NCX contributes little to the Ca2+ paradox, whereas inhibition of NCX during Ca2+ depletion improves SR Ca2+ loading, and is associated with reduced incidence of Ca2+ paradox in mouse ventricular myocytes. PMID:20718730

Responsibility for Curriculum Evaluation in Centralized Systems.

ERIC Educational Resources Information Center

Deschamp, Phil; McGaw, Barry

1979-01-01

While responsibility for curriculum development in Australia is devolving to the local level, the state systems, in the name of accountability, are retaining responsibility for curriculum evaluation. This article examines the curriculum centralization/decentralization patterns in Australia's states, points out the paradoxes in such systems, and…

How Much Does a Half-Kilogram of Water "Weigh"?

ERIC Educational Resources Information Center

Koumaras, Panagiotis; Pierratos, Theodoros

2015-01-01

Many educators have utilized the phenomenon of the so-called "hydrostatic paradox" to actively engage students in classroom instructional activities related to hydrostatic equilibrium. Various approaches requiring different levels of mathematical knowledge have been proposed in the literature to provide students clear explanations of…

Physical and chemical stratigraphy suggest small or absent glacioeustatic variation during formation of the Paradox Basin cyclothems

NASA Astrophysics Data System (ADS)

Dyer, Blake; Maloof, Adam C.

2015-06-01

The Paradox Basin cyclothems previously have been interpreted as Milankovitch style glacial-interglacial cycles from the Late Paleozoic Ice Age, but an unambiguous test for a glacioeustatic origin has not been conducted. A high resolution coupled chemical and physical stratigraphic analysis of two outcrop sections and three core segments provides new evidence that supports either minor sea level change of several meters or an autocyclic mechanism for parasequence formation. High amplitude sea level change is ruled out by the scale of thin top-negative isotopic meteoric diagenesis trends associated with parasequence tops and subaerial exposure fabrics. Isotopic gradients from shelf (light) to basin (heavy) indicate that parasequences are deposited diachronously, with isotopes of more distal sections recording increased basin restriction. These results support the idea that the late Pennsylvanian was a prolonged period of relatively static eustasy, agreeing with recent studies in the western USA. The methods provide a new set of tools and context for extracting environmental information from cyclic upward shallowing carbonate parasequences.

The "Paradox of Interdisciplinarity" in Australian Research Governance

ERIC Educational Resources Information Center

Woelert, Peter; Millar, Victoria

2013-01-01

This paper identifies what can be called the "paradox of interdisciplinarity" (Weingart 2000) in Australian higher education research governance and explores some of its constitutive dimensions. In the Australian context, the paradox of interdisciplinarity primarily concerns the proliferation of a programmatic discourse of…

The Simpson's paradox unraveled

PubMed Central

Hernán, Miguel A; Clayton, David; Keiding, Niels

2011-01-01

Background In a famous article, Simpson described a hypothetical data example that led to apparently paradoxical results. Methods We make the causal structure of Simpson's example explicit. Results We show how the paradox disappears when the statistical analysis is appropriately guided by subject-matter knowledge. We also review previous explanations of Simpson's paradox that attributed it to two distinct phenomena: confounding and non-collapsibility. Conclusion Analytical errors may occur when the problem is stripped of its causal context and analyzed merely in statistical terms. PMID:21454324

No information or horizon paradoxes for Th. Smiths

NASA Astrophysics Data System (ADS)

Maes, Christian

2015-10-01

The Statistical mechanician in the street (our Th. Smiths) must be surprised upon hearing popular versions of some of today's most discussed paradoxes in astronomy and cosmology. In fact, rather standard reminders of the meaning of thermal probabilities in statistical mechanics appear to answer the horizon problem (one of the major motivations for inflation theory) and the information paradox (related to black hole physics), at least as they are usually presented. Still the paradoxes point to interesting gaps in our statistical understanding of (quantum) gravitational effects.

Greenberger-Horne-Zeilinger paradoxes from qudit graph states.

PubMed

Tang, Weidong; Yu, Sixia; Oh, C H

2013-03-08

One fascinating way of revealing quantum nonlocality is the all-versus-nothing test due to Greenberger, Horne, and Zeilinger (GHZ) known as the GHZ paradox. So far genuine multipartite and multilevel GHZ paradoxes are known to exist only in systems containing an odd number of particles. Here we shall construct GHZ paradoxes for an arbitrary number (greater than 3) of particles with the help of qudit graph states on a special kind of graphs, called GHZ graphs. Furthermore, based on the GHZ paradox arising from a GHZ graph, we derive a Bell inequality with two d-outcome observables for each observer, whose maximal violation attained by the corresponding graph state, and a Kochen-Specker inequality testing the quantum contextuality in a state-independent fashion.

Molecular interference of fibrin’s divalent polymerization mechanism enables modulation of multiscale material properties

PubMed Central

Brown, Ashley C.; Baker, Stephen; Douglas, Alison; Keating, Mark; Alvarez-Elizondo, Martha; Botvinick, Elliot; Guthold, Martin; Barker, Thomas H.

2015-01-01

Protein based polymers provide an exciting and complex landscape for tunable natural biomaterials through modulation of molecular level interactions. Here we demonstrate the ability to modify protein polymer structural and mechanical properties at multiple length scales by molecular ‘interference’ of fibrin’s native polymerization mechanism. We have previously reported that engagement of fibrin’s polymerization ‘hole b’, also known as ‘b-pockets’, through PEGylated complimentary ‘knob B’ mimics can increase fibrin network porosity but also, somewhat paradoxically, increase network stiffness. Here, we explore the possible mechanistic underpinning of this phenomenon through characterization of the effects of knob B-fibrin interaction at multiple length scales from molecular to bulk polymer. Despite its weak monovalent binding affinity for fibrin, addition of both knob B and PEGylated knob B at concentrations near the binding coefficient, Kd, increased fibrin network porosity, consistent with the reported role of knob B-hole b interactions in promoting lateral growth of fibrin fibers. Addition of PEGylated knob B decreases the extensibility of single fibrin fibers at concentrations near its Kd but increases extensibility of fibers at concentrations above its Kd. The data suggest this bimodal behavior is due to the individual contributions knob B, which decreases fiber extensibility, and PEG, which increase fiber extensibility. Taken together with laser trap-based microrheological and bulk rheological analyses of fibrin polymers, our data strongly suggests that hole b engagement increases in single fiber stiffness that translates to higher storage moduli of fibrin polymers despite their increased porosity. These data point to possible strategies for tuning fibrin polymer mechanical properties through modulation of single fiber mechanics. PMID:25725552

Zeno Meets Modern Science

NASA Astrophysics Data System (ADS)

Silagadze, Z. K.

2005-10-01

``No one has ever touched Zeno without refuting him''. We will not refute Zeno in this paper. Instead we review some unexpected encounters of Zeno with modern science. The paper begins with a brief biography of Zeno of Elea followed by his famous paradoxes of motion. Reflections on continuity of space and time lead us to Banach and Tarski and to their celebrated paradox, which is in fact not a paradox at all but a strict mathematical theorem, although very counterintuitive. Quantum mechanics brings another flavour in Zeno paradoxes. Quantum Zeno and anti-Zeno effects are really paradoxical but now experimental facts. Then we discuss supertasks and bifurcated supertasks. The concept of localisation leads us to Newton and Wigner and to interesting phenomenon of quantum revivals. At last we note that the paradoxical idea of timeless universe, defended by Zeno and Parmenides at ancient times, is still alive in quantum gravity. The list of references that follows is necessarily incomplete but we hope it will assist interested reader to fill in details.

Implementing Parrondo's paradox with two-coin quantum walks

NASA Astrophysics Data System (ADS)

Rajendran, Jishnu; Benjamin, Colin

2018-02-01

Parrondo's paradox is ubiquitous in games, ratchets and random walks. The apparent paradox, devised by J. M. R. Parrondo, that two losing games A and B can produce a winning outcome has been adapted in many physical and biological systems to explain their working. However, proposals on demonstrating Parrondo's paradox using quantum walks failed for a large number of steps. In this work, we show that instead of a single coin if we consider a two-coin initial state which may or may not be entangled, we can observe a genuine Parrondo's paradox with quantum walks. Furthermore, we focus on reasons for this and pin down the asymmetry in initial two-coin state or asymmetry in shift operator, either of which is necessary for observing a genuine Parrondo's paradox. We extend our work to a three-coin initial state too with similar results. The implications of our work for observing quantum ratchet-like behaviour using quantum walks are also discussed.

Implementing Parrondo’s paradox with two-coin quantum walks

PubMed Central

Rajendran, Jishnu

2018-01-01

Parrondo’s paradox is ubiquitous in games, ratchets and random walks. The apparent paradox, devised by J. M. R. Parrondo, that two losing games A and B can produce a winning outcome has been adapted in many physical and biological systems to explain their working. However, proposals on demonstrating Parrondo’s paradox using quantum walks failed for a large number of steps. In this work, we show that instead of a single coin if we consider a two-coin initial state which may or may not be entangled, we can observe a genuine Parrondo’s paradox with quantum walks. Furthermore, we focus on reasons for this and pin down the asymmetry in initial two-coin state or asymmetry in shift operator, either of which is necessary for observing a genuine Parrondo’s paradox. We extend our work to a three-coin initial state too with similar results. The implications of our work for observing quantum ratchet-like behaviour using quantum walks are also discussed. PMID:29515873

The Role of Field Artillery in Counterinsurgency Operations

DTIC Science & Technology

2006-06-16

muscle and bone fiber of the officer and noncommissioned officer corps of our Army a level of experience that is unprecedented. ( TVT 22-147 2002, Meigs...Department of Defense. . 2002. TVT 22-147, Armed peacekeepers in Bosnia: The paradoxical mission. Fort Leavenworth, KS: Department of Defense

The Peer Influence Paradox: Friendship Quality and Deviancy Training Within Male Adolescent Friendships.

ERIC Educational Resources Information Center

Poulin, Francois; Dishion, Thomas J.; Haas, Eric

1999-01-01

Tested hypothesis that primary-influence processes in adolescent friendships are social interactional and that quality of friendship has little to do with development of delinquent behavior. Found that antisocial boys showed poor-quality friendships and low levels of relationship quality. (Author)

Navigating Instructional Dialectics: Empirical Exploration of Paradox in Teaching

ERIC Educational Resources Information Center

Thompson, Blair; Rudick, C. Kyle; Kerssen-Griep, Jeff; Golsan, Kathryn

2018-01-01

Navigating contradiction represents an integral part of the teaching process. While educational literature has discussed the paradoxes that teachers experience in the classroom, minimal empirical research has analyzed the strategies teachers employ to address these paradoxes. Using relational dialectics as a theoretical framework for understanding…

Barn and Pole Paradox: Revisited

ERIC Educational Resources Information Center

Cacioppo, Robert; Gangopadhyaya, Asim

2012-01-01

Paradoxes have played great instructive roles in many cultures. They provide an excellent paradigm for teaching concepts that require deep reflection. In this article, the authors present two different paradoxes related to the length contraction in special relativity and explain their resolution. They hope that these two Gedanken experiments and…

Characterization of auxin-binding proteins from zucchini plasma membrane

NASA Technical Reports Server (NTRS)

Hicks, G. R.; Rice, M. S.; Lomax, T. L.

1993-01-01

We have previously identified two auxin-binding polypeptides in plasma membrane (PM) preparations from zucchini (Cucurbita pepo L.) (Hicks et al. 1989, Proc. Natl. Acad. Sci. USA 86, 4948-4952). These polypeptides have molecular weights of 40 kDa and 42 kDa and label specifically with the photoaffinity auxin analog 5-N3-7-3H-IAA (azido-IAA). Azido-IAA permits both the covalent and radioactive tagging of auxin-binding proteins and has allowed us to characterize further the 40-kDa and 42-kDa polypeptides, including the nature of their attachment to the PM, their relationship to each other, and their potential function. The azido-IAA-labeled polypeptides remain in the pelleted membrane fraction following high-salt and detergent washes, which indicates a tight and possibly integral association with the PM. Two-dimensional electrophoresis of partially purified azido-IAA-labeled protein demonstrates that, in addition to the major isoforms of the 40-kDa and 42-kDa polypeptides, which possess isoelectric points (pIs) of 8.2 and 7.2, respectively, several less abundant isoforms that display unique pIs are apparent at both molecular masses. Tryptic and chymotryptic digestion of the auxin-binding proteins indicates that the 40-kDa and 42-kDa polypeptides are closely related or are modifications of the same polypeptide. Phase extraction with the nonionic detergent Triton X-114 results in partitioning of the azido-IAA-labeled polypeptides into the aqueous (hydrophilic) phase. This apparently paradoxical behavior is also exhibited by certain integral membrane proteins that aggregate to form channels. The results of gel filtration indicate that the auxin-binding proteins do indeed aggregate strongly and that the polypeptides associate to form a dimer or multimeric complex in vivo. These characteristics are consistent with the hypothesis that the 40-kDa and 42-kDa polypeptides are subunits of a multimeric integral membrane protein which has an auxin-binding site, and which may possess transporter or channel function.

Characterization of auxin-binding proteins from zucchini plasma membrane.

PubMed

Hicks, G R; Rice, M S; Lomax, T L

1993-01-01

We have previously identified two auxin-binding polypeptides in plasma membrane (PM) preparations from zucchini (Cucurbita pepo L.) (Hicks et al. 1989, Proc. Natl. Acad. Sci. USA 86, 4948-4952). These polypeptides have molecular weights of 40 kDa and 42 kDa and label specifically with the photoaffinity auxin analog 5-N3-7-3H-IAA (azido-IAA). Azido-IAA permits both the covalent and radioactive tagging of auxin-binding proteins and has allowed us to characterize further the 40-kDa and 42-kDa polypeptides, including the nature of their attachment to the PM, their relationship to each other, and their potential function. The azido-IAA-labeled polypeptides remain in the pelleted membrane fraction following high-salt and detergent washes, which indicates a tight and possibly integral association with the PM. Two-dimensional electrophoresis of partially purified azido-IAA-labeled protein demonstrates that, in addition to the major isoforms of the 40-kDa and 42-kDa polypeptides, which possess isoelectric points (pIs) of 8.2 and 7.2, respectively, several less abundant isoforms that display unique pIs are apparent at both molecular masses. Tryptic and chymotryptic digestion of the auxin-binding proteins indicates that the 40-kDa and 42-kDa polypeptides are closely related or are modifications of the same polypeptide. Phase extraction with the nonionic detergent Triton X-114 results in partitioning of the azido-IAA-labeled polypeptides into the aqueous (hydrophilic) phase. This apparently paradoxical behavior is also exhibited by certain integral membrane proteins that aggregate to form channels. The results of gel filtration indicate that the auxin-binding proteins do indeed aggregate strongly and that the polypeptides associate to form a dimer or multimeric complex in vivo. These characteristics are consistent with the hypothesis that the 40-kDa and 42-kDa polypeptides are subunits of a multimeric integral membrane protein which has an auxin-binding site, and which may possess transporter or channel function.

Identification of the binding sites for ubiquinone and inhibitors in the Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae by photoaffinity labeling

PubMed Central

Ito, Takeshi; Ninokura, Satoshi; Kitazumi, Yuki; Mezic, Katherine G.; Cress, Brady F.; Koffas, Mattheos A. G.; Morgan, Joel E.; Barquera, Blanca; Miyoshi, Hideto

2017-01-01

The Na+-pumping NADH-quinone oxidoreductase (Na+-NQR) is the first enzyme of the respiratory chain and the main ion transporter in many marine and pathogenic bacteria, including Vibrio cholerae. The V. cholerae Na+-NQR has been extensively studied, but its binding sites for ubiquinone and inhibitors remain controversial. Here, using a photoreactive ubiquinone PUQ-3 as well as two aurachin-type inhibitors [125I]PAD-1 and [125I]PAD-2 and photoaffinity labeling experiments on the isolated enzyme, we demonstrate that the ubiquinone ring binds to the NqrA subunit in the regions Leu-32–Met-39 and Phe-131–Lys-138, encompassing the rear wall of a predicted ubiquinone-binding cavity. The quinolone ring and alkyl side chain of aurachin bound to the NqrB subunit in the regions Arg-43–Lys-54 and Trp-23–Gly-89, respectively. These results indicate that the binding sites for ubiquinone and aurachin-type inhibitors are in close proximity but do not overlap one another. Unexpectedly, although the inhibitory effects of PAD-1 and PAD-2 were almost completely abolished by certain mutations in NqrB (i.e. G140A and E144C), the binding reactivities of [125I]PAD-1 and [125I]PAD-2 to the mutated enzymes were unchanged compared with those of the wild-type enzyme. We also found that photoaffinity labeling by [125I]PAD-1 and [125I]PAD-2, rather than being competitively suppressed in the presence of other inhibitors, is enhanced under some experimental conditions. To explain these apparently paradoxical results, we propose models for the catalytic reaction of Na+-NQR and its interactions with inhibitors on the basis of the biochemical and biophysical results reported here and in previous work. PMID:28298441

Antifreeze proteins govern the precipitation of trehalose in a freezing-avoiding insect at low temperature.

PubMed

Wen, Xin; Wang, Sen; Duman, John G; Arifin, Josh Fnu; Juwita, Vonny; Goddard, William A; Rios, Alejandra; Liu, Fan; Kim, Soo-Kyung; Abrol, Ravinder; DeVries, Arthur L; Henling, Lawrence M

2016-06-14

The remarkable adaptive strategies of insects to extreme environments are linked to the biochemical compounds in their body fluids. Trehalose, a versatile sugar molecule, can accumulate to high levels in freeze-tolerant and freeze-avoiding insects, functioning as a cryoprotectant and a supercooling agent. Antifreeze proteins (AFPs), known to protect organisms from freezing by lowering the freezing temperature and deferring the growth of ice, are present at high levels in some freeze-avoiding insects in winter, and yet, paradoxically are found in some freeze-tolerant insects. Here, we report a previously unidentified role for AFPs in effectively inhibiting trehalose precipitation in the hemolymph (or blood) of overwintering beetle larvae. We determine the trehalose level (29.6 ± 0.6 mg/mL) in the larval hemolymph of a beetle, Dendroides canadensis, and demonstrate that the hemolymph AFPs are crucial for inhibiting trehalose crystallization, whereas the presence of trehalose also enhances the antifreeze activity of AFPs. To dissect the molecular mechanism, we examine the molecular recognition between AFP and trehalose crystal interfaces using molecular dynamics simulations. The theory corroborates the experiments and shows preferential strong binding of the AFP to the fast growing surfaces of the sugar crystal. This newly uncovered role for AFPs may help explain the long-speculated role of AFPs in freeze-tolerant species. We propose that the presence of high levels of molecules important for survival but prone to precipitation in poikilotherms (their body temperature can vary considerably) needs a companion mechanism to prevent the precipitation and here present, to our knowledge, the first example. Such a combination of trehalose and AFPs also provides a novel approach for cold protection and for trehalose crystallization inhibition in industrial applications.

Antifreeze proteins govern the precipitation of trehalose in a freezing-avoiding insect at low temperature

PubMed Central

Wen, Xin; Wang, Sen; Duman, John G.; Arifin, Josh Fnu; Juwita, Vonny; Goddard, William A.; Rios, Alejandra; Liu, Fan; Kim, Soo-Kyung; Abrol, Ravinder; DeVries, Arthur L.; Henling, Lawrence M.

2016-01-01

The remarkable adaptive strategies of insects to extreme environments are linked to the biochemical compounds in their body fluids. Trehalose, a versatile sugar molecule, can accumulate to high levels in freeze-tolerant and freeze-avoiding insects, functioning as a cryoprotectant and a supercooling agent. Antifreeze proteins (AFPs), known to protect organisms from freezing by lowering the freezing temperature and deferring the growth of ice, are present at high levels in some freeze-avoiding insects in winter, and yet, paradoxically are found in some freeze-tolerant insects. Here, we report a previously unidentified role for AFPs in effectively inhibiting trehalose precipitation in the hemolymph (or blood) of overwintering beetle larvae. We determine the trehalose level (29.6 ± 0.6 mg/mL) in the larval hemolymph of a beetle, Dendroides canadensis, and demonstrate that the hemolymph AFPs are crucial for inhibiting trehalose crystallization, whereas the presence of trehalose also enhances the antifreeze activity of AFPs. To dissect the molecular mechanism, we examine the molecular recognition between AFP and trehalose crystal interfaces using molecular dynamics simulations. The theory corroborates the experiments and shows preferential strong binding of the AFP to the fast growing surfaces of the sugar crystal. This newly uncovered role for AFPs may help explain the long-speculated role of AFPs in freeze-tolerant species. We propose that the presence of high levels of molecules important for survival but prone to precipitation in poikilotherms (their body temperature can vary considerably) needs a companion mechanism to prevent the precipitation and here present, to our knowledge, the first example. Such a combination of trehalose and AFPs also provides a novel approach for cold protection and for trehalose crystallization inhibition in industrial applications. PMID:27226297

The Chinese Classroom Paradox: A Cross-Cultural Comparison of Teacher Controlling Behaviors

ERIC Educational Resources Information Center

Zhou, Ning; Lam, Shui-Fong; Chan, Kam Chi

2012-01-01

Chinese classrooms present an intriguing paradox to the claim of self-determination theory that autonomy facilitates learning. Chinese teachers appear to be controlling, but Chinese students do not have poor academic performance in international comparisons. The present study addressed this paradox by examining the cultural differences in…

New Paradoxes of Risky Decision Making

ERIC Educational Resources Information Center

Birnbaum, Michael H.

2008-01-01

During the last 25 years, prospect theory and its successor, cumulative prospect theory, replaced expected utility as the dominant descriptive theories of risky decision making. Although these models account for the original Allais paradoxes, 11 new paradoxes show where prospect theories lead to self-contradiction or systematic false predictions.…

Virtue Acquisition: The Paradox of Striving

ERIC Educational Resources Information Center

Snow, Nancy

2016-01-01

Aristotelian-inspired accounts of virtue acquisition stress guided practice and habituated action to develop virtue. This emphasis on action can lead to the "paradox of striving". The paradox occurs when we try too hard to act well and thereby spoil our efforts. I identify four forms of striving--forcing, impulsivity, overthinking, and…

A new transport phenomenon in nanostructures: a mesoscopic analog of the Braess paradox encountered in road networks

PubMed Central

2012-01-01

The Braess paradox, known for traffic and other classical networks, lies in the fact that adding a new route to a congested network in an attempt to relieve congestion can degrade counterintuitively the overall network performance. Recently, we have extended the concept of the Braess paradox to semiconductor mesoscopic networks, whose transport properties are governed by quantum physics. In this paper, we demonstrate theoretically that, alike in classical systems, congestion plays a key role in the occurrence of a Braess paradox in mesoscopic networks. PMID:22913510

Paradoxical response preceding control of Scedosporium apiospermum mycetoma with posaconazole treatment.

PubMed

Béraud, Guillaume; Desbois, Nicole; Coyo, Caroline; Quist, Danièle; Rozé, Benoit; Savorit, Luc; Cabié, André

2015-01-01

Mycetoma is a chronic granulomatous infection that is difficult to treat, notably when due to fungi such as Scedosporium apiospermum. Recent antifungal agents could be an option, but cases are rarely reported, and none with posaconazole. Paradoxical responses, defined as initial clinical worsening despite appropriate treatment, are common in tuberculosis but rare in deep mycoses in non-immunocompromised hosts. Hence, paradoxical responses in context other than mycobacterial infection in an immunocompromised host could provide insights into the pathophysiology and the optimal strategy for treatment. We report the first case of a mycetoma caused by S. apiospermum with bone involvement treated with posaconazole, and the paradoxical response observed at the beginning of the treatment. As with mycobacterial infections, a paradoxical response in deep mycosis could represent the earliest marker of therapeutic efficacy.

Patent foramen ovale and paradoxical embolization: a historical perspective.

PubMed

Lippmann, H; Rafferty, T

1993-01-01

The use of transesophageal echocardiography for intraoperative management of critically ill patients allows for routine evaluation of foramen ovale patency. The high prevalence of preoperatively unrecognized flow-patency of this structure has led investigators to emphasize the potential for paradoxical embolization in any patient undergoing anesthesia. This perspective led us to research earliest documentation of paradoxical embolization through a patent foramen ovale as a historical issue with present day relevance. This report examines the 1877 text of Julius Cohnheim in which he described a fatal case of paradoxical embolization to the middle meningeal artery. The 1880 manuscript of Moritz Litten documenting paradoxical embolization to the lower extremity is also presented. Both translations, to our knowledge, represent the first such representations of both the original 1877 edition of Cohnheim's work and Litten's journal article.

Parrondo's games based on complex networks and the paradoxical effect.

PubMed

Ye, Ye; Wang, Lu; Xie, Nenggang

2013-01-01

Parrondo's games were first constructed using a simple tossing scenario, which demonstrates the following paradoxical situation: in sequences of games, a winning expectation may be obtained by playing the games in a random order, although each game (game A or game B) in the sequence may result in losing when played individually. The available Parrondo's games based on the spatial niche (the neighboring environment) are applied in the regular networks. The neighbors of each node are the same in the regular graphs, whereas they are different in the complex networks. Here, Parrondo's model based on complex networks is proposed, and a structure of game B applied in arbitrary topologies is constructed. The results confirm that Parrondo's paradox occurs. Moreover, the size of the region of the parameter space that elicits Parrondo's paradox depends on the heterogeneity of the degree distributions of the networks. The higher heterogeneity yields a larger region of the parameter space where the strong paradox occurs. In addition, we use scale-free networks to show that the network size has no significant influence on the region of the parameter space where the strong or weak Parrondo's paradox occurs. The region of the parameter space where the strong Parrondo's paradox occurs reduces slightly when the average degree of the network increases.

The effect of smoking on lung cancer: ethnic differences and the smoking paradox

PubMed Central

2016-01-01

The objectives of this review were to determine whether the smoking paradox still exists and to summarize possible explanations for the smoking paradox. Based on published data, we compared the risk of cigarette smoking for lung cancer in Western and Asian countries. We extracted data from the relevant studies about annual tobacco consumption, lung cancer mortality rates according to smoking status from each country, and possible explanations for the smoking paradox. A significantly greater risk of lung cancer death was found among current smokers in Asian countries than among nonsmokers, with relative risks (RRs) of 4.0 to 4.6 for Koreans, 3.7 to 5.1 for Japanese, and 2.4 to 6.5 for Chinese. Although a significantly greater risk of lung cancer was present among current smokers in Asian countries, the RRs in Asian countries were much lower than those reported in Western countries (range, 9.4 to 23.2). Possible explanations for the smoking paradox included epidemiologic characteristics, such as the smoking amount, age at smoking initiation, and the use of filtered or mild tobacco. The smoking paradox definitely exists, but may be explained by major epidemiologic characteristics. Therefore, the smoking paradox should not be interpreted as indicating that tobacco is safer or less harmful for Asians. PMID:28092929

The fermi paradox is neither Fermi's nor a paradox.

PubMed

Gray, Robert H

2015-03-01

The so-called Fermi paradox claims that if technological life existed anywhere else, we would see evidence of its visits to Earth--and since we do not, such life does not exist, or some special explanation is needed. Enrico Fermi, however, never published anything on this topic. On the one occasion he is known to have mentioned it, he asked "Where is everybody?"--apparently suggesting that we do not see extraterrestrials on Earth because interstellar travel may not be feasible, but not suggesting that intelligent extraterrestrial life does not exist or suggesting its absence is paradoxical. The claim "they are not here; therefore they do not exist" was first published by Michael Hart, claiming that interstellar travel and colonization of the Galaxy would be inevitable if intelligent extraterrestrial life existed, and taking its absence here as proof that it does not exist anywhere. The Fermi paradox appears to originate in Hart's argument, not Fermi's question. Clarifying the origin of these ideas is important, because the Fermi paradox is seen by some as an authoritative objection to searching for evidence of extraterrestrial intelligence--cited in the U.S. Congress as a reason for killing NASA's SETI program on one occasion. But evidence indicates that it misrepresents Fermi's views, misappropriates his authority, deprives the actual authors of credit, and is not a valid paradox.

A case at last for age-phased reduction in equity.

PubMed Central

Samuelson, P A

1989-01-01

Maximizing expected utility over a lifetime leads one who has constant relative risk aversion and faces random-walk securities returns to be "myopic" and hold the same fraction of portfolio in equities early and late in life--a defiance of folk wisdom and casual introspection. By assuming one needs to assure at retirement a minimum ("subsistence") level of wealth, the present analysis deduces a pattern of greater risk-taking when young than when old. When a subsistence minimum is needed at every period of life, the rentier paradoxically is least risk tolerant in youth--the Robert C. Merton paradox that traces to the decline with age of the present discounted value of the subsistence-consumption requirements. Conversely, the decline with age of capitalized human capital reverses the Merton effect. PMID:2813438

Paradoxical topiramate-induced hyperphagia successfully treated with phentermine in a woman with migraine.

PubMed

Johnson, Jacinta L; Rolan, Paul E

2015-08-01

We report a 49-year-old female migraineur who experienced paradoxical hyperphagia and concurrent intrusive food thoughts leading to rapid weight gain and a substantial increase in waist circumference. A significant reduction in migraine frequency was also observed during topiramate treatment, a widely used migraine prophylactic agent which is generally associated with weight loss. Withdrawal of topiramate saw appetite return to baseline levels, however, migraine frequency was again increased. Topiramate was reinitiated in combination with phentermine, a drug indicated for weight management, without reoccurrence of adverse effects. Migraine control was maintained and progressive weight loss ensued. Combination treatment with phentermine may be a useful strategy should other patients experience this adverse reaction while gaining therapeutic anti-migraine benefit from topiramate. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Paradox of Decentralizing Schools: Lessons from Business, Government, and the Catholic Church.

ERIC Educational Resources Information Center

Murphy, Jerome T.

1989-01-01

By the year 2000, school decentralization could become another unfortunate, ineffectual pendulum swing. According to this article, a dynamic, ever-changing system of decentralization and centralization balances the benefits of local administrative autonomy with the pursuit of unified goals and helps each leadership level understand its…

Beneficial and paradoxical roles of selenium at nutritional levels of intake in healthspan and longevity

USDA-ARS?s Scientific Manuscript database

Accumulation of damage to the genome and macromolecules is a hallmark of aging, age-associated degeneration, and genome instability syndromes. Although the processes of aging are irreversible, they can be modulated by genome maintenance pathways and environmental factors such as diet. Selenium (Se) ...

Mind Your p's and Alphas.

ERIC Educational Resources Information Center

Stallings, William M.

In the educational research literature alpha, the a priori level of significance, and p, the a posteriori probability of obtaining a test statistic of at least a certain value when the null hypothesis is true, are often confused. Explanations for this confusion are offered. Paradoxically, alpha retains a prominent place in textbook discussions of…

The Gross and Net Effects of Primary School Denomination on Pupil Performance

ERIC Educational Resources Information Center

Driessen, Geert; Agirdag, Orhan; Merry, Michael S.

2016-01-01

Notwithstanding dramatically low levels of professed religiosity in Western Europe, the religious school sector continues to thrive. One explanation for this paradox is that nowadays parents choose religious schools primarily for their higher academic reputation. Empirical evidence for this presumed denominational advantage is mixed. We examine…

Discriminatory Air Pollution

ERIC Educational Resources Information Center

McCaull, Julian

1976-01-01

Described are the patterns of air pollution in certain large urban areas. Persons in poverty, in occupations below the management or professional level, in low-rent districts, and in black population are most heavily exposed to air pollution. Pollution paradoxically is largely produced by high energy consuming middle-and upper-class households.…

The Paradox of Children and Life Satisfaction

ERIC Educational Resources Information Center

Becchetti, Leonardo; Ricca, Elena Giachin; Pelloni, Alessandra

2013-01-01

Empirical analyses of the determinants of life satisfaction routinely include the number of children as one of the socio demographic controls, without explicitly considering that, for a given household income, more children imply a lower level of income per family member. The variable "number of children" then often attracts a negative…

The Politics of Gender Segregation and Women's Access to Higher Education in the Islamic Republic of Iran: The Interplay of Repression and Resistance

ERIC Educational Resources Information Center

Rezai-Rashti, Goli M.

2015-01-01

One of the significant achievements of the Islamic Republic of Iran has been the increasing access of women to all levels of education. This paper focuses on women's access to higher education and its unexpected and paradoxical outcomes. Today women in Iran represent over 60% of university students at the undergraduate level. Against the dominant…

Paradox Lost? No, Paradox Found! Reply to Tomasello and Akhtar (2003).

ERIC Educational Resources Information Center

Naigles, Letitia R.

2003-01-01

Asserts that the posited paradox between infancy and toddlerhood language was not eliminated by Tomasello and Akhtar's appeal to infants' robust statistical learning abilities. Maintains that scrutiny of their studies supports the resolution that abstracting linguistic form is easy for infants and that toddlers find it difficult to integrate…

Killing Mosquitoes and Keeping Practice: Teacher Education as Sustaining Paradox

ERIC Educational Resources Information Center

Keiser, David Lee

2013-01-01

The moral and ethical charge of teaching and teacher education includes sustaining equanimity and paradox, and maintaining poise amongst contradicting policies and interests. This paper draws upon the wisdom of the Tao Te Ching to address some paradoxes in education and teacher preparation. Specifically, the article looks at four chapters of the…

The Role of Cognitive Disposition in Re-Examining the Privacy Paradox: A Neuroscience Study

ERIC Educational Resources Information Center

Mohammed, Zareef

2017-01-01

The privacy paradox is a phenomenon whereby individuals continue to disclose their personal information, contrary to their claim of concerns for the privacy of their personal information. This study investigated the privacy paradox to better understand individuals' decisions to disclose or withhold their personal information. The study argued that…

CROWN GALL INCIDENCE: SEEDLING PARADOX WALNUT ROOTSTOCK VERSUS OWN-ROOTED ENGLISH WALNUT TREES

USDA-ARS?s Scientific Manuscript database

Seedling Paradox (Juglans hindsii x J. regia) has been the rootstock of choice for English walnut in California because of its vigor and greater tolerance of wet soil conditions. However, seedling Paradox rootstock is highly susceptible to crown gall, a disease caused by the soil-borne bacterium Agr...

The Power of Why: Engaging the Goal Paradox in Program Evaluation

ERIC Educational Resources Information Center

Friedman, Victor J.; Rothman, Jay; Withers, Bill

2006-01-01

Clearly defined and measurable goals are commonly considered prerequisites for effective evaluation. Goal setting, however, presents a paradox to evaluators because it takes place at the interface of rationality and values. The objective of this article is to demonstrate a method for unlocking this paradox by making goal setting a process of…

What Do Police Academy Instructors and STEM Teachers Have in Common? The "Mission Paradox"

ERIC Educational Resources Information Center

Even Zahav, Anat; Shahar, Sigalit; Hazzan, Orit

2016-01-01

This article presents the "Mission Paradox," shared by two public sector organizations in Israel: the police training system and the post-primary STEM education system. The "Mission Paradox" was identified in data analysis of two doctoral studies, which implemented a qualitative methodology. The study's purpose was to analyze…

An Applet for the Investigation of Simpson's Paradox

ERIC Educational Resources Information Center

Schneiter, Kady; Symanzik, Jurgen

2013-01-01

This article describes an applet that facilitates investigation of Simpson's Paradox in the context of a number of real and hypothetical data sets. The applet builds on the Baker-Kramer graphical representation for Simpson's Paradox. The implementation and use of the applet are explained. This is followed by a description of how the applet has…

Yule-Simpson's Paradox in Research

ERIC Educational Resources Information Center

Goltz, Heather Honore; Smith, Matthew Lee

2010-01-01

Yule (1903) and Simpson (1951) described a statistical paradox that occurs when data is aggregated. In such situations, aggregated data may reveal a trend that directly contrasts those of sub-groups trends. In fact, the aggregate data trends may even be opposite in direction of sub-group trends. To reveal Yule-Simpson's paradox (YSP)-type…

Biochemical pharmacology of paradoxical sleep

PubMed Central

Gaillard, J. -M.

1983-01-01

1 The role of noradrenergic cells in the regulation of paradoxical sleep is still controversial, and experimental data have given rise to contradictory interpretations. 2 Early investigations focused primarily on chemical neurotransmissions. However, the process of information transmission between cells involves many other factors, and the cell surface is an important site for transduction of messages into modifications of the activity of postsynaptic cells. 3 α-adrenoceptors are believed to play an important role in the control of wakefulness and paradoxical sleep. Experimental evidence suggests that physiological modulation of receptor sensitivity, possibly by specific neuro-modulators, may be a key mechanism in synaptic transmission. 4 In the investigation of the mechanisms involved in paradoxical sleep regulation, lesions of the locus coeruleus have given equivocal results. Collateral inhibition, probably mediated by α2-adrenoceptors, appears to be a powerful mechanism. The exact temporal relationship between noradrenergic cell activation and paradoxical sleep production is not established, but 5-HT appears to be involved. Differences between paradoxical sleep and waking may be related to a physiological modulation of α2-adrenoceptor sensitivity. PMID:6140943

Aristotle Meets Zeno: Psychophysiological Evidence

PubMed Central

Papageorgiou, Charalabos; Stachtea, Xanthi; Papageorgiou, Panos; Alexandridis, Antonio T.

2016-01-01

This study, a tribute to Aristotle's 2400 years, used a juxtaposition of valid Aristotelian arguments to the paradoxes formulated by Zeno the Eleatic, in order to investigate the electrophysiological correlates of attentional and /or memory processing effects in the course of deductive reasoning. Participants undertook reasoning tasks based on visually presented arguments which were either (a) valid (Aristotelian) statements or (b) paradoxes. We compared brain activation patterns while participants maintained the premises / conclusions of either the valid statements or the paradoxes in working memory (WM). Event-related brain potentials (ERPs), specifically the P300 component of ERPs, were recorded during the WM phase, during which participants were required to draw a logical conclusion regarding the correctness of the valid syllogisms or the paradoxes. During the processing of paradoxes, results demonstrated a more positive event-related potential deflection (P300) across frontal regions, whereas processing of valid statements was associated with noticeable P300 amplitudes across parieto-occipital regions. These findings suggest that paradoxes mobilize frontal attention mechanisms, while valid deduction promotes parieto-occipital activity associated with attention and/or subsequent memory processing. PMID:28033333

Aristotle Meets Zeno: Psychophysiological Evidence.

PubMed

Papageorgiou, Charalabos; Stachtea, Xanthi; Papageorgiou, Panos; Alexandridis, Antonio T; Tsaltas, Eleftheria; Angelopoulos, Elias

2016-01-01

This study, a tribute to Aristotle's 2400 years, used a juxtaposition of valid Aristotelian arguments to the paradoxes formulated by Zeno the Eleatic, in order to investigate the electrophysiological correlates of attentional and /or memory processing effects in the course of deductive reasoning. Participants undertook reasoning tasks based on visually presented arguments which were either (a) valid (Aristotelian) statements or (b) paradoxes. We compared brain activation patterns while participants maintained the premises / conclusions of either the valid statements or the paradoxes in working memory (WM). Event-related brain potentials (ERPs), specifically the P300 component of ERPs, were recorded during the WM phase, during which participants were required to draw a logical conclusion regarding the correctness of the valid syllogisms or the paradoxes. During the processing of paradoxes, results demonstrated a more positive event-related potential deflection (P300) across frontal regions, whereas processing of valid statements was associated with noticeable P300 amplitudes across parieto-occipital regions. These findings suggest that paradoxes mobilize frontal attention mechanisms, while valid deduction promotes parieto-occipital activity associated with attention and/or subsequent memory processing.

Desire versus Efficacy in Smokers’ Paradoxical Reactions to Pictorial Health Warnings for Cigarettes

PubMed Central

Romer, Daniel; Peters, Ellen; Strasser, Andrew A.; Langleben, Daniel

2013-01-01

Pictorial health warnings on cigarette packs create aversive emotional reactions to smoking and induce thoughts about quitting; however, contrary to models of health behavior change, they do not appear to alter intentions to quit smoking. We propose and test a novel model of intention to quit an addictive habit such as smoking (the efficacy-desire model) that can explain this paradoxical effect. At the core of the model is the prediction that self-efficacy and desire to quit an addictive habit are inversely related. We tested the model in an online experiment that randomly exposed smokers (N = 3297) to a cigarette pack with one of three increasing levels of warning intensity. The results supported the model’s prediction that despite the effects of warnings on aversion to smoking, intention to quit smoking is an inverted U-shape function of the smoker’s self-efficacy for quitting. In addition, smokers with greater (lesser) quit efficacy relative to smoking efficacy increase (decrease) intentions to quit. The findings show that previous failures to observe effects of pictorial warning labels on quit intentions can be explained by the contradictory individual differences that warnings produce. Thus, the model explains the paradoxical finding that quit intentions do not change at the population level, even though smokers recognize the implications of warnings. The model suggests that pictorial warnings are effective for smokers with stronger quit-efficacy beliefs and provides guidance for how cigarette warnings and tobacco control strategies can be designed to help smokers quit. PMID:23383006

Negative affect and drinking drivers: a review and conceptual model linking dissonance, efficacy and negative affect to risk and motivation for change.

PubMed

Wells-Parker, Elisabeth; Mann, Robert E; Dill, Patricia L; Stoduto, Gina; Shuggi, Rania; Cross, Ginger W

2009-05-01

This review summarizes evidence on negative affect among drinking drivers. Elevations in negative affect, including depressed mood, anxiety and hostility, have long been noted in convicted drinking drivers, and recent evidence suggests an association between negative affect and driving after drinking in the general population. Previous efforts to understand the significance of this negative affective state have ranged from suggestions that it may play a causal role in drinking driving to suggestions that it may interfere with response to treatment and remedial interventions. Recent studies have uncovered an important paradox involving negative affect among convicted drinking drivers (hereafter DUI offenders). DUI offenders with high levels of negative affect recidivated more frequently following a DUI program than did those reporting no or minimal negative affect. However, when a brief supportive motivational intervention was added to the program, offenders with high negative affect levels showed lower recidivism rates than did those with no or minimal negative affect. The review includes studies from the general literature on alcohol treatment in which the same negative affect paradox was reported. In an attempt to understand this paradox, we present a conceptual model involving well-established psychological processes, with a focus on salient discrepancy, the crucial component of cognitive dissonance. In this model, negative affect plays an important role in motivating both continued high-risk drinking as well as therapeutic change. This model suggests that links between motivational states and negative affective processes may be more complex than previously thought. Implications for intervention with DUI offenders are discussed.

Fluoxetine disrupts motivation and GABAergic signaling in adolescent female hamsters.

PubMed

Shannonhouse, John L; DuBois, Dustin W; Fincher, Annette S; Vela, Alejandra M; Henry, Morgan M; Wellman, Paul J; Frye, Gerald D; Morgan, Caurnel

2016-08-01

Initial antidepressant treatment can paradoxically worsen symptoms in depressed adolescents by undetermined mechanisms. Interestingly, antidepressants modulate GABAA receptors, which mediate paradoxical effects of other therapeutic drugs, particularly in females. Although the neuroanatomic site of action for this paradox is unknown, elevated GABAA receptor signaling in the nucleus accumbens can disrupt motivation. We assessed fluoxetine's effects on motivated behaviors in pubescent female hamsters - anhedonia in the reward investigational preference (RIP) test as well as anxiety in the anxiety-related feeding/exploration conflict (AFEC) test. We also assessed accumbal signaling by RT-PCR and electrophysiology. Fluoxetine initially worsened motivated behaviors at puberty, relative to adulthood. It also failed to improve these behaviors as pubescent hamsters transitioned into adulthood. Low accumbal mRNA levels of multiple GABAA receptor subunits and GABA-synthesizing enzyme, GAD67, assessed by RT-PCR, suggested low GABAergic tone at puberty. Nonetheless, rapid fluoxetine-induced reductions of α5GABAA receptor and BDNF mRNA levels at puberty were consistent with age-related differences in GABAergic responses to fluoxetine and disruption of the motivational state. Whole-cell patch clamping of accumbal slices also suggested low GABAergic tone by the low amplitude of miniature inhibitory postsynaptic currents (mIPSCs) at puberty. It also confirmed age-related differences in GABAergic responses to fluoxetine. Specifically, fluoxetine potentiated mIPSC amplitude and frequency at puberty, but attenuated the amplitude during adulthood. These results implicate GABAergic tone and GABAA receptor plasticity in adverse motivational responses and resistance to fluoxetine during adolescence. Copyright © 2016 Elsevier Inc. All rights reserved.

Proteasomal interaction as a critical activity modulator of the human constitutive androstane receptor

PubMed Central

Chen, Tao; Laurenzana, Elizabeth M.; Coslo, Denise M.; Chen, Fengming; Omiecinski, Curtis J.

2014-01-01

The CAR (constitutive androstane receptor; NR1I3) is a critical xenobiotic sensor that regulates xenobiotic metabolism, drug clearance, energy and lipid homoeostasis, cell proliferation and development. Although constitutively active, in hepatocytes CAR is normally held quiescent through a tethering mechanism in the cytosol, anchored to a protein complex that includes several components, including heat-shock protein 90. Release and subsequent nuclear translocation of CAR is triggered through either direct binding to ligand activators such as CITCO {6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime} or through indirect chemical activation, such as with PB (phenobarbital). In the present study, we demonstrate that proteasomal inhibition markedly disrupts CAR function, repressing CAR nuclear trafficking, disrupting CAR’s interaction with nuclear co-activators and inhibiting induction of CAR target gene responses in human primary hepatocytes following treatment with either PB or CITCO. Paradoxically, these effects occur following accumulation of ubiquitinated hCAR (human CAR). Furthermore, a non-proteolytic function was indicated by its interaction with a SUG1 (suppressor for Gal1), a subunit of the 26S proteasome. Taken together, these data demonstrate that the proteasome complex functions at multiple levels to regulate the functional biology of hCAR activity. PMID:24224465

Paradoxical Personality and Academic Achievement in College Students From Buenos Aires

PubMed Central

Freiberg Hoffmann, Agustín; Fernández Liporace, María Mercedes

2015-01-01

This paper presents a study on paradoxical personality, defined as a distinctive feature in creative persons, developed with 350 college students from Buenos Aires. Goals aimed at describing and analysing possible significant differences of paradoxical traits in students from diverse majors representing seven different fields of study, and examining the relationship between each bipolar trait and academic achievement. The sample was composed of 7 groups (n = 50 by group) representing fields of study typically offered in public universities, Biology, Computer Science, Engineering, Law, Nutrition, Psychology, and History of Art. Analyses by career provided descriptive information about students of these majors, concerning their paradoxical personality profiles. Correlational studies verified significant associations between academic achievement and most paradoxical traits in majors such as Computer Science, Nutrition and Psychology. Results are discussed regarding practical outcomes and teaching programs. PMID:27247680

Towards an Einstein-Podolsky-Rosen paradox between two macroscopic atomic ensembles at room temperature

NASA Astrophysics Data System (ADS)

He, Q. Y.; Reid, M. D.

2013-06-01

Experiments have reported the entanglement of two spatially separated macroscopic atomic ensembles at room temperature (Krauter et al 2011 Phys. Rev. Lett. 107 080503; Julsgaard et al 2001 Nature 413 400). We show how an Einstein-Podolsky-Rosen (EPR) paradox is realizable with this experiment. Our proposed test involves violation of an inferred Heisenberg uncertainty principle, which is a sufficient condition for an EPR paradox. This is a stronger test of nonlocality than entanglement. Our proposal would enable the first definitive confirmation of quantum EPR paradox correlations between two macroscopic objects at room temperature. This is a necessary intermediate step towards a nonlocal experiment with causal measurement separations. As well as having fundamental significance, the realization of an atomic EPR paradox could provide a resource for novel applications in quantum technology.

'Bedside assessment' of acute hantavirus infections and their possible classification into the spectrum of haemophagocytic syndromes.

PubMed

Clement, J; Colson, P; Saegeman, V; Lagrou, K; Van Ranst, M

2016-07-01

Hantavirus infections, recently renamed 'hantavirus fever' (HTVF), belong to the most common but also most underestimated zoonoses in the world. A small number of reports described the so-called 'lipid paradox' in HTVF, i.e. the striking contrast between a very low serum total cholesterol and/or high-density lipoprotein cholesterol (HDLc), and a paradoxical concomitant hypertriglyceridaemia. In a prospective study, with patients being their own control after illness, we wanted to verify if this quick and easy 'bedside test' was robust enough to warrant a preliminary diagnosis of acute kidney injury (AKI) caused by HTVF. The study cohort consisted of 58 Belgian cases (mean age 44 years), admitted with varying degrees of AKI and of thrombocytopaenia, both characteristic for presumptive HTVF. All cases were sero-confirmed as having acute HTVF. At or shortly after hospital admission, a significant (p < 0.001) decrease of total cholesterol and HDLc was found in comparison with normalised levels in the same cohort, quantified a few days after spontaneous AKI recovery. Conversely, fasting triglyceride levels during HTVF infection were significantly (p < 0.001) higher during illness than after recovery. This 'lipid paradox' was most outspoken in severe HTVF cases, often accompanying, or even predicting, major kidney or lung complications. Thus, this 'bedside assessment' seems to hold even promise for presumptive diagnosis of more severe so-called 'hantavirus cardio-pulmonary syndrome' (HCPS) cases, mostly described hitherto in the New World. In more severe AKI cases, the mean total cholesterol was significantly lower (p = 0.02) than in milder cases, i.e. cases with peak serum creatinine levels of < 1.5 mg/dL. Thrombocytopaenia, generally accepted as the severity index in HTVF, appeared, moreover, significantly correlated with serum levels of total cholesterol (R = 0.52, p < 0.001) and with serum levels of HDLc (R = 0.45, p < 0.01). A link with the novel clinical entity of haemophagocytic syndromes, also characterised by manifest hypertriglyceridaemia, is discussed.

Role of aberrant striatal dopamine D1 receptor/cAMP/protein kinase A/DARPP32 signaling in the paradoxical calming effect of amphetamine.

PubMed

Napolitano, Francesco; Bonito-Oliva, Alessandra; Federici, Mauro; Carta, Manolo; Errico, Francesco; Magara, Salvatore; Martella, Giuseppina; Nisticò, Robert; Centonze, Diego; Pisani, Antonio; Gu, Howard H; Mercuri, Nicola B; Usiello, Alessandro

2010-08-18

Attention deficit/hyperactivity disorder (ADHD) is characterized by inattention, impulsivity, and motor hyperactivity. Several lines of research support a crucial role for the dopamine transporter (DAT) gene in this psychiatric disease. Consistently, the most commonly prescribed medications in ADHD treatment are stimulant drugs, known to preferentially act on DAT. Recently, a knock-in mouse [DAT-cocaine insensitive (DAT-CI)] has been generated carrying a cocaine-insensitive DAT that is functional but with reduced dopamine uptake function. DAT-CI mutants display enhanced striatal extracellular dopamine levels and basal motor hyperactivity. Herein, we showed that DAT-CI animals present higher striatal dopamine turnover, altered basal phosphorylation state of dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP32) at Thr75 residue, but preserved D(2) receptor (D(2)R) function. However, although we demonstrated that striatal D(1) receptor (D(1)R) is physiologically responsive under basal conditions, its stimulus-induced activation strikingly resulted in paradoxical electrophysiological, behavioral, and biochemical responses. Indeed, in DAT-CI animals, (1) striatal LTP was completely disrupted, (2) R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) treatment induced paradoxical motor calming effects, and (3) SKF 81297 administration failed to increase cAMP/protein kinase A (PKA)/DARPP32 signaling. Such biochemical alteration selectively affected dopamine D(1)Rs since haloperidol, by blocking the tonic inhibition of D(2)R, unmasked a normal activation of striatal adenosine A(2A) receptor-mediated cAMP/PKA/DARPP32 cascade in mutants. Most importantly, our studies highlighted that amphetamine, nomifensine, and bupropion, through increased striatal dopaminergic transmission, are able to revert motor hyperactivity of DAT-CI animals. Overall, our results suggest that the paradoxical motor calming effect induced by these drugs in DAT-CI mutants depends on selective aberrant phasic activation of D(1)R/cAMP/PKA/DARPP32 signaling in response to increased striatal extracellular dopamine levels.

A simple explanation of the classic hydrostatic paradox

NASA Astrophysics Data System (ADS)

Kontomaris, Stylianos-Vasileios; Malamou, Anna

2016-07-01

An interesting problem in fluid mechanics, with significant educational importance, is the classic hydrostatic paradox. The hydrostatic paradox states the fact that in different shaped containers, with the same base area, which are filled with a liquid of the same height, the applied force by the liquid on the base of each container is exactly the same. However, if the shape of the container is different, the amount of the liquid (and as a consequence the weight) can greatly vary. In this paper, a simple explanation of the hydrostatic paradox, specifically designed and implemented for educational purposes regarding secondary education, is provided.

Introducing the Levinthal's Protein Folding Paradox and Its Solution

ERIC Educational Resources Information Center

Martínez, Leandro

2014-01-01

The protein folding (Levinthal's) paradox states that it would not be possible in a physically meaningful time to a protein to reach the native (functional) conformation by a random search of the enormously large number of possible structures. This paradox has been solved: it was shown that small biases toward the native conformation result…

Bolzano's Approach to the Paradoxes of Infinity: Implications for Teaching

ERIC Educational Resources Information Center

Waldegg, Guillermina

2005-01-01

In this paper we analyze excerpts of "Paradoxes of the Infinite", the posthumous work of Bernard Bolzano (1781-1848), in order to show that Georg Cantor's (1845-1918) approach to the problem of defining actual mathematical infinity is not the most natural. In fact, Bolzano's approach to the paradoxes of infinity is more intuitive, while remaining…

The Use of Paradoxical Intention in the Treatment of Panic Attacks.

ERIC Educational Resources Information Center

Dattilio, Frank M.

1987-01-01

Discusses the counseling use of paradoxical intention, in which clients are told to perform responses that seem incompatible with the goal for which they are seeking help. The use of paradoxical intention in the treatment of panic attacks is described and a case example is included. The nature and implementation of the technique are discussed.…

Ethics and Social Justice within the New DEEL: Addressing the Paradox of Control/Democracy

ERIC Educational Resources Information Center

Shapiro, Joan Poliner

2006-01-01

This paper addresses the ethical and social justice implications of an educational movement called, The New DEEL (Democratic Ethical Educational Leadership). In particular, this paper emphasizes the ethical underpinnings of this movement by focusing on the paradox in the form of the dyad of control/democracy. This important paradox is developed…

(Information) Paradox Regained? A Brief Comment on Maudlin on Black Hole Information Loss

NASA Astrophysics Data System (ADS)

Manchak, J. B.; Weatherall, James Owen

2018-04-01

We discuss some recent work by Tim Maudlin concerning Black Hole Information Loss. We argue, contra Maudlin, that there is a paradox, in the straightforward sense that there are propositions that appear true, but which are incompatible with one another. We discuss the significance of the paradox and Maudlin's response to it.

Two Paradoxes of the "Seller's Market" of Chinese Higher Education

ERIC Educational Resources Information Center

Huang, J.

2005-01-01

In recent years, two "paradoxes" have emerged in the "seller's market" of Chinese higher education. One is a strong demand for buying educational services and a weak demand for consumption; a second is the coexistence of an entry to the seller's market and an exit point from the buyer's market. These two "paradoxes"…

Shade Tolerance of Festuca paradoxa Desv., a Cool-Season Grass Native to North America

Treesearch

Nadia Navarrete-Tindall; Larry Mechlin; J. W. Van Sambeek

2003-01-01

Paradox grass (Festuca paradoxa Desv.) is a native cool-season grass found in prairies and forest openings. Paradox grass has not been included in tree plantings. To determine paradox grass adaptation to shaded environmmts, we established a pot experiment in the shade laboratory at the University of Missouri Horticulture and Agroforestry Research...

Facing Paradox Everyday: A Heideggerian Approach to the Ethics of Teaching

ERIC Educational Resources Information Center

d'Agnese, Vasco

2016-01-01

In this paper, I wish to offer insight into the role of paradox in teaching. I will do so by analyzing teachers' everyday work, taking a qualitative approach and constructing a small-scale empirical study. Philosophically, my attempt is framed by Heidegger's thought. Drawing from research data, I argue the following: (a) paradoxes and dilemmas are…

A Simple Explanation of the Classic Hydrostatic Paradox

ERIC Educational Resources Information Center

Kontomaris, Stylianos-Vasileios; Malamou, Anna

2016-01-01

An interesting problem in fluid mechanics, with significant educational importance, is the classic hydrostatic paradox. The hydrostatic paradox states the fact that in different shaped containers, with the same base area, which are filled with a liquid of the same height, the applied force by the liquid on the base of each container is exactly the…

Ebselen induces mitochondrial permeability transition because of its interaction with adenine nucleotide translocase.

PubMed

Pavón, Natalia; Correa, Francisco; Buelna-Chontal, Mabel; Hernández-Esquivel, Luz; Chávez, Edmundo

2015-10-15

Mitochondrial permeability transition is a process established through massive Ca(2+) load in addition to an inducer reagent. Ebselen (Ebs), an antioxidant seleno compound, has been introduced as a reagent which inhibits mitochondrial dysfunction induced by permeability transition. Paradoxically enough, it has been shown that Ebs may also be able to induce the opening of the mitochondrial non-selective pores. This study was performed with the purpose of establishing the membrane system involved in Ebs-induced pore opening. Permeability transition was appraised by analyzing the following: i) matrix Ca(2+) release, and mitochondrial swelling, ii) efflux of cytochrome c, and iii) the inhibition of superoxide dismutase. All of these adverse reactions were inhibited by N-ethylmaleimide and cyclosporin A. At concentrations from 5 to 20 μM, we found that Ebs induces non-specific membrane permeability. Remarkably, Ebs blocks the binding of the fluorescent reagent eosin-5-maleimide to the thiol groups of the adenine nucleotide translocase. Based on the above, it is tempting to hypothesize that Ebs induces pore opening through its binding to the ADP/ATP carrier. Copyright © 2015 Elsevier Inc. All rights reserved.

Insulin signalling mechanisms for triacylglycerol storage.

PubMed

Czech, M P; Tencerova, M; Pedersen, D J; Aouadi, M

2013-05-01

Insulin signalling is uniquely required for storing energy as fat in humans. While de novo synthesis of fatty acids and triacylglycerol occurs mostly in liver, adipose tissue is the primary site for triacylglycerol storage. Insulin signalling mechanisms in adipose tissue that stimulate hydrolysis of circulating triacylglycerol, uptake of the released fatty acids and their conversion to triacylglycerol are poorly understood. New findings include (1) activation of DNA-dependent protein kinase to stimulate upstream stimulatory factor (USF)1/USF2 heterodimers, enhancing the lipogenic transcription factor sterol regulatory element binding protein 1c (SREBP1c); (2) stimulation of fatty acid synthase through AMP kinase modulation; (3) mobilisation of lipid droplet proteins to promote retention of triacylglycerol; and (4) upregulation of a novel carbohydrate response element binding protein β isoform that potently stimulates transcription of lipogenic enzymes. Additionally, insulin signalling through mammalian target of rapamycin to activate transcription and processing of SREBP1c described in liver may apply to adipose tissue. Paradoxically, insulin resistance in obesity and type 2 diabetes is associated with increased triacylglycerol synthesis in liver, while it is decreased in adipose tissue. This and other mysteries about insulin signalling and insulin resistance in adipose tissue make this topic especially fertile for future research.

Immune reconstitution inflammatory syndrome associated with toxoplasmic encephalitis in HIV-infected patients.

PubMed

van Bilsen, Ward P H; van den Berg, Charlotte H S B; Rijnders, Bart J A; Brinkman, Kees; Mulder, Jan W; Gelinck, Luc B S; Hoepelman, Andy I M; Wit, Ferdinand W N M; van de Beek, Diederik; Prins, Jan M

2017-06-19

To investigate the incidence and risk factors of immune reconstitution inflammatory syndrome (IRIS) associated with toxoplasmic encephalitis (TE) in patients starting combination antiretroviral therapy (cART). A historical multicenter cohort study. We included all HIV-infected patients diagnosed with toxoplasmic encephalitis in six Dutch hospitals between 1996 and 2016. Diagnosis of TE-IRIS was made using predefined IRIS criteria. We distinguished paradoxical TE-IRIS (worsening of underlying treated infection) from unmasking TE-IRIS (unmasking of subclinical infection after start of cART). We compared CD4 cell count, plasma viral load and timing of cART initiation between patients with and without paradoxical TE-IRIS. A total of 211 toxoplasmic encephalitis cases were included. Among 143 cases at risk for paradoxical TE-IRIS, we identified five cases of paradoxical TE-IRIS (3.5%). In six other cases, we could not differentiate paradoxical TE-IRIS from recurrence of disease due to inadequate secondary Toxoplasma prophylaxis. There was no difference in time between start of toxoplasmic encephalitis treatment and cART initiation for patients who did or did not develop paradoxical TE-IRIS (P = 0.50). Within the group of 2228 patients who started cART while having a CD4 cell count below 200 × 10 cells/l and receiving adequate primary prophylaxis, we identified eight cases of unmasking TE-IRIS (0.36%). Unmasking TE-IRIS could not be differentiated from a newly occurring toxoplasmic encephalitis in six other patients, as they were not receiving adequate primary prophylaxis against Toxoplasma. Unmasking TE-IRIS was rare in this cohort, whereas paradoxical TE-IRIS did occur more often. We found no relationship between the timing of cART initiation and the occurrence of paradoxical TE-IRIS.

Quantum Bayesian networks with application to games displaying Parrondo's paradox

NASA Astrophysics Data System (ADS)

Pejic, Michael

Bayesian networks and their accompanying graphical models are widely used for prediction and analysis across many disciplines. We will reformulate these in terms of linear maps. This reformulation will suggest a natural extension, which we will show is equivalent to standard textbook quantum mechanics. Therefore, this extension will be termed quantum. However, the term quantum should not be taken to imply this extension is necessarily only of utility in situations traditionally thought of as in the domain of quantum mechanics. In principle, it may be employed in any modelling situation, say forecasting the weather or the stock market---it is up to experiment to determine if this extension is useful in practice. Even restricting to the domain of quantum mechanics, with this new formulation the advantages of Bayesian networks can be maintained for models incorporating quantum and mixed classical-quantum behavior. The use of these will be illustrated by various basic examples. Parrondo's paradox refers to the situation where two, multi-round games with a fixed winning criteria, both with probability greater than one-half for one player to win, are combined. Using a possibly biased coin to determine the rule to employ for each round, paradoxically, the previously losing player now wins the combined game with probabilitygreater than one-half. Using the extended Bayesian networks, we will formulate and analyze classical observed, classical hidden, and quantum versions of a game that displays this paradox, finding bounds for the discrepancy from naive expectations for the occurrence of the paradox. A quantum paradox inspired by Parrondo's paradox will also be analyzed. We will prove a bound for the discrepancy from naive expectations for this paradox as well. Games involving quantum walks that achieve this bound will be presented.

The paradox of strategic environmental assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bidstrup, Morten, E-mail: bidstrup@plan.aau.dk; Hansen, Anne Merrild, E-mail: merrild@plan.aau.dk

Strategic Environmental Assessment (SEA) is a tool that can facilitate sustainable development and improve decision-making by introducing environmental concern early in planning processes. However, various international studies conclude that current planning practice is not taking full advantage of the tool, and we therefore define the paradox of SEA as the methodological ambiguity of non-strategic SEA. This article explores causality through at three-step case study on aggregates extraction planning in Denmark, which consists of a document analysis; a questionnaire survey and follow-up communication with key planners. Though the environmental reports on one hand largely lack strategic considerations, practitioners express an inherentmore » will for strategy and reveal that their SEAs in fact have been an integrated part of the planning process. Institutional context is found to be the most significant barrier for a strategy and this suggests that non-strategic planning setups can prove more important than non-strategic planning in SEA practice. Planners may try to execute strategy within the confinements of SEA-restricted planning contexts; however, such efforts can be overlooked if evaluated by a narrow criterion for strategy formation. Consequently, the paradox may also spark from challenged documentation. These findings contribute to the common understanding of SEA quality; however, further research is needed on how to communicate and influence the strategic options which arguably remain inside non-strategic planning realities. - Highlights: • International studies conclude that SEAs are not strategic. = The paradox of SEA. • Even on the highest managerial level, some contexts do not leave room for strategy. • Non-strategic SEA can derive from challenged documentation. • Descriptive and emergent strategy formation can, in practice, be deemed non-strategic.« less

A direct thrombin inhibitor suppresses protein C activation and factor Va degradation in human plasma: Possible mechanisms of paradoxical enhancement of thrombin generation.

PubMed

Kamisato, Chikako; Furugohri, Taketoshi; Morishima, Yoshiyuki

2016-05-01

We have demonstrated that antithrombin (AT)-independent thrombin inhibitors paradoxically increase thrombin generation (TG) in human plasma in a thrombomodulin (TM)- and protein C (PC)-dependent manner. We determined the effects of AT-independent thrombin inhibitors on the negative-feedback system, activation of PC and production and degradation of factor Va (FVa), as possible mechanisms underlying the paradoxical enhancement of TG. TG in human plasma containing 10nM TM was assayed by means of the calibrated automated thrombography. As an index of PC activation, plasma concentration of activated PC-PC inhibitor complex (aPC-PCI) was measured. The amounts of FVa heavy chain and its degradation product (FVa(307-506)) were examined by western blotting. AT-independent thrombin inhibitors, melagatran and dabigatran (both at 25-600nM) and 3-30μg/ml active site-blocked thrombin (IIai), increased peak levels of TG. Melagatran, dabigatran and IIai significantly decreased plasma concentration of aPC-PCI complex at 25nM or more, 75nM or more, and 10 and 30μg/ml, respectively. Melagatran (300nM) significantly increased FVa and decreased FVa(307-506). In contrast, a direct factor Xa inhibitor edoxaban preferentially inhibited thrombin generation (≥25nM), and higher concentrations were required to inhibit PC activation (≥150nM) and FVa degradation (300nM). The present study suggests that the inhibitions of protein C activation and subsequent degradation of FVa and increase in FVa by antithrombin-independent thrombin inhibitors may contribute to the paradoxical TG enhancement, and edoxaban may inhibit PC activation and FVa degradation as a result of TG suppression. Copyright © 2016 Elsevier Ltd. All rights reserved.

The evolution of health status and chronic conditions in Catalonia, 1994-2006: the paradox of health revisited using the Blinder - Oaxaca decomposition.

PubMed

García-Altés, Anna; Pinilla, Jaime; Ortún, Vicente

2011-05-23

The paradox of health refers to the improvement in objective measures of health and the increase in the reported prevalence of chronic conditions. The objective of this paper is to test the paradox of health in Catalonia from 1994 to 2006. Longitudinal cross-sectional study using the Catalonia Health Interview Survey of 1994 and 2006. The approach used was the three-fold Blinder - Oaxaca decomposition, separating the part of the differential in mean visual analogue scale value (VAS) due to group differences in the predictors (prevalence effect), due to differences in the coefficients (severity effect), and an interaction term. Variables included were the VAS value, education level, labour status, marital status, all common chronic conditions over the two cross-sections, and a variable for non-common chronic conditions and other conditions. Sample weights have been applied. Results show that there is an increase in mean VAS for men aged 15-44, and a decrease in mean VAS for women aged 65-74 and 75 and more. The increase in mean VAS for men aged 15-44 could be explained by a decrease in the severity effect, which offsets the increase in the prevalence effect. The decrease in mean VAS for women aged 65-74 and 75 and more could be explained by an increase in the prevalence effect, which does not offset the decrease in the severity effect. The results of the present analysis corroborate the paradox of health hypothesis for the population of Catalonia, and highlight the need to be careful when measuring population health over time, as well as their usefulness to detect population's perceptions.

The evolution of health status and chronic conditions in Catalonia, 1994-2006: the paradox of health revisited using the Blinder - Oaxaca decomposition

PubMed Central

2011-01-01

Background The paradox of health refers to the improvement in objective measures of health and the increase in the reported prevalence of chronic conditions. The objective of this paper is to test the paradox of health in Catalonia from 1994 to 2006. Methods Longitudinal cross-sectional study using the Catalonia Health Interview Survey of 1994 and 2006. The approach used was the three-fold Blinder - Oaxaca decomposition, separating the part of the differential in mean visual analogue scale value (VAS) due to group differences in the predictors (prevalence effect), due to differences in the coefficients (severity effect), and an interaction term. Variables included were the VAS value, education level, labour status, marital status, all common chronic conditions over the two cross-sections, and a variable for non-common chronic conditions and other conditions. Sample weights have been applied. Results Results show that there is an increase in mean VAS for men aged 15-44, and a decrease in mean VAS for women aged 65-74 and 75 and more. The increase in mean VAS for men aged 15-44 could be explained by a decrease in the severity effect, which offsets the increase in the prevalence effect. The decrease in mean VAS for women aged 65-74 and 75 and more could be explained by an increase in the prevalence effect, which does not offset the decrease in the severity effect. Conclusions The results of the present analysis corroborate the paradox of health hypothesis for the population of Catalonia, and highlight the need to be careful when measuring population health over time, as well as their usefulness to detect population's perceptions. PMID:21605384

TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis.

PubMed

Conrad, Curdin; Di Domizio, Jeremy; Mylonas, Alessio; Belkhodja, Cyrine; Demaria, Olivier; Navarini, Alexander A; Lapointe, Anne-Karine; French, Lars E; Vernez, Maxime; Gilliet, Michel

2018-01-02

Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2-5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced T-cell numbers, when compared to classical psoriasis. Anti-TNF treatment prolongs type I interferon production by pDCs through inhibition of their maturation. The resulting type I interferon overexpression is responsible for the skin phenotype of paradoxical psoriasis, which, unlike classical psoriasis, is independent of T cells. These findings indicate that paradoxical psoriasis represents an ongoing overactive innate inflammatory process, driven by pDC-derived type I interferon that does not lead to T-cell autoimmunity.

Solution of Supplee's submarine paradox through special and general relativity

NASA Astrophysics Data System (ADS)

Vieira, R. S.

2016-12-01

In 1989 Supplee described an apparent relativistic paradox on which a submarine seems to sink to observers at rest within the ocean, but it rather seems to float in the submarine proper frame. In this letter, we show that the paradox arises from a misuse of the Archimedes principle in the relativistic case. Considering first the special relativity, we show that any relativistic force field can be written in the Lorentz form, so that it can always be decomposed into a static (electric-like) and a dynamic (magnetic-like) part. These gravitomagnetic effects provide a relativistic formulation of Archimedes principle, from which the paradox is explained. Besides, if the curved spacetime on the vicinity of the Earth is taken into account, we show that the gravitational force exerted by the Earth on a moving body must increase with the speed of the body. The submarine paradox is then analyzed again with this speed-dependent gravitational force.

Stokes paradox in electronic Fermi liquids

NASA Astrophysics Data System (ADS)

Lucas, Andrew

2017-03-01

The Stokes paradox is the statement that in a viscous two-dimensional fluid, the "linear response" problem of fluid flow around an obstacle is ill posed. We present a simple consequence of this paradox in the hydrodynamic regime of a Fermi liquid of electrons in two-dimensional metals. Using hydrodynamics and kinetic theory, we estimate the contribution of a single cylindrical obstacle to the global electrical resistance of a material, within linear response. Momentum relaxation, present in any realistic electron liquid, resolves the classical paradox. Nonetheless, this paradox imprints itself in the resistance, which can be parametrically larger than predicted by Ohmic transport theory. We find a remarkably rich set of behaviors, depending on whether or not the quasiparticle dynamics in the Fermi liquid should be treated as diffusive, hydrodynamic, or ballistic on the length scale of the obstacle. We argue that all three types of behavior are observable in present day experiments.

Structure-function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination.

PubMed

Zhao, Liang; Ng, Ee Ting; Davidson, Tara-Lynne; Longmuss, Enya; Urschitz, Johann; Elston, Marlee; Moisyadi, Stefan; Bowles, Josephine; Koopman, Peter

2014-08-12

The mammalian sex-determining factor SRY comprises a conserved high-mobility group (HMG) box DNA-binding domain and poorly conserved regions outside the HMG box. Mouse Sry is unusual in that it includes a C-terminal polyglutamine (polyQ) tract that is absent in nonrodent SRY proteins, and yet, paradoxically, is essential for male sex determination. To dissect the molecular functions of this domain, we generated a series of Sry mutants, and studied their biochemical properties in cell lines and transgenic mouse embryos. Sry protein lacking the polyQ domain was unstable, due to proteasomal degradation. Replacing this domain with irrelevant sequences stabilized the protein but failed to restore Sry's ability to up-regulate its key target gene SRY-box 9 (Sox9) and its sex-determining function in vivo. These functions were restored only when a VP16 transactivation domain was substituted. We conclude that the polyQ domain has important roles in protein stabilization and transcriptional activation, both of which are essential for male sex determination in mice. Our data disprove the hypothesis that the conserved HMG box domain is the only functional domain of Sry, and highlight an evolutionary paradox whereby mouse Sry has evolved a novel bifunctional module to activate Sox9 directly, whereas SRY proteins in other taxa, including humans, seem to lack this ability, presumably making them dependent on partner proteins(s) to provide this function.

Administration of riluzole to the basolateral amygdala facilitates fear extinction in rats.

PubMed

Sugiyama, Azusa; Yamada, Misa; Saitoh, Akiyoshi; Oka, Jun-Ichiro; Yamada, Mitsuhiko

2018-01-15

A general understanding exists that inhibition of glutamatergic neurotransmission in the basolateral amygdala (BLA) impairs fear extinction in rodents. Surprisingly, we recently found that systemic administration of riluzole, which has been shown to inhibit the glutamatergic system, facilitates extinction learning in rats with a preconditioned contextual fear response. However, the mechanisms underlying this paradoxical effect of riluzole remain unclear. In this study, adult male Wistar rats were bilaterally cannulated in the BLA to examine the effects of intra-BLA administration of riluzole. We also compared the effects of riluzole with those of d-cycloserine, a partial agonist at the glycine-binding region of the N-methyl-d-aspartate (NMDA) receptor. In this study, intra-BLA administration of either riluzole or d-cycloserine facilitated extinction learning of contextual fear in conditioned rats. In addition, both riluzole and d-cycloserine enhanced the acquisition of recognition memory in the same model. However, intra-BLA injections of riluzole, but not d-cycloserine, had a potent anxiolytic-like effect when investigated using an elevated plus-maze test. Our findings suggest that riluzole-induced facilitation of extinction learning in rats with a preconditioned contextual fear reflects an indirect effect, resulting from the intra-BLA administration of the drug, and might not be directly related to inhibition of glutamatergic signaling. Further research is needed to clarify the mechanisms underlying the paradoxical effect of riluzole on fear extinction learning observed in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

Does life satisfaction change in old age: results from an 8-year longitudinal study.

PubMed

Gana, Kamel; Bailly, Nathalie; Saada, Yaël; Joulain, Michèle; Alaphilippe, Daniel

2013-07-01

The unexpected positive relationship between aging and happiness was called "the paradox of well-being," which is still a matter of debate. This study examined longitudinal change in life satisfaction (LS) in older adults. LS was assessed with the satisfaction with life scale, in a sample of individuals (N = 899; aged 62-95 years, at first occasion; M = 72.73, SD = 5.68) for a period of 8 years (5 waves of data). A multiple indicator (e.g., second order) growth modeling was used to assess change in LS. Findings from both unconditional and conditional model (in which time-invariant, i.e., age, gender, and education, and time-varying, i.e., self-perceived health, covariates were incorporated in the model) indicated a linear increase in LS for the 8-year period. As expected, the results showed significant random variation in both intercept and slope, indicating that participants start at different levels and change at different rates. Our findings contribute to the debate concerning the paradox of well-being, which calls for explanation. There are few theories that provide some explanation (e.g., the socioemotional selectivity theory). However, to enhance researchers' understanding of developmental changes that contribute to the paradox of well-being, a more integrative theoretical model is needed.

Psychological stress declines rapidly from age 50 in the United States: Yet another well-being paradox.

PubMed

Stone, Arthur A; Schneider, Stefan; Broderick, Joan E

2017-12-01

Although there is evidence that evaluative subjective well-being (e.g., life satisfaction) shows a U-shaped pattern with highest satisfaction in the youngest and oldest years and lowest in the middle years of adulthood, much less is known about experiential well-being. We explore a negative indicator of experiential well-being (perceived stress), examine its association with age, and explore possible determinants of the age pattern. Using Gallup-Healthways survey data of over 1.5 million U.S. respondents, we analyzed a question asking about stress yesterday and demographic determinants of the pattern. To confirm this pattern, data on stress was analyzed from the American Time Use Survey and data on distress was analyzed from the Health and Retirement Survey. We show that ratings of daily, perceived stressfulness yield a paradox, with high levels from the 20's through about age 50, followed by a precipitous decline through the 70's. Data from the other two surveys confirmed the age pattern for stress. Regressions with the Gallup-Healthways data statistically controlled several third-variables, yet none substantially altered the pattern. We argue that this new experiential well-being pattern informs us about aging in the US and the "paradox" calls out for explanation. Copyright © 2017 Elsevier Inc. All rights reserved.

Low incidence of paradoxical reductions in HDL-C levels in dyslipidemic patients treated with fenofibrate alone or in combination with ezetimibe or ezetimibe/simvastatin

PubMed Central

2011-01-01

Background Fibrates have been reported to cause paradoxical decreases in HDL-C in certain patients. Design and methods This post-hoc analysis explored the frequency/magnitude of HDL-C reductions in a pooled database of mixed dyslipidemic patients (LDL-C:3.4-5.7 mmol/L;TG:1.7-5.7 mmol/L) receiving placebo (PBO), fenofibrate (FENO), ezetimibe plus FENO (EZE+FENO), or EZE/simvastatin plus FENO (EZE/SIMVA+FENO) for 12 weeks. Results PBO-treated patients had the highest incidence of HDL-C reductions from baseline (45%) compared with patients taking FENO (14%), EZE+FENO (9%), or EZE/SIMVA+FENO (9%). Reductions <30% reflected natural variability since the largest reduction in HDL-C approached 30% in the PBO group. Only 3 patients exhibited HDL-C reductions ≥30% (i.e., 2 patients in the FENO group and 1 in the EZE+FENO group). There were no differences in demographic/biochemical characteristics between patients with and without HDL-C reductions. Conclusions The incidence of paradoxical HDL-C reductions was low in mixed dyslipidemic patients receiving FENO alone or combined with EZE or EZE/SIMVA. Trial registrations Clinicaltrials.gov: NCT00092560 and NCT00092573 PMID:22087637

Software Support Measurement and Estimating for Oracle Database Applications Using Mark II Function Points

DTIC Science & Technology

1992-12-01

36 V.33. Coe ncint of De minstioi ........................ 37 V3A. F-Raio .................................... 37 V3.5... de ations. Instructions ae defined as lines of code or card images. Thus, a line containin two or mome souce statements counts as one instruction; a...understand the productivity paradox, recall de concept of virtual machines. When a higher level machine groups ogether many instructm of a lower level

Neural Mechanisms Underlying Paradoxical Performance for Monetary Incentives Are Driven by Loss Aversion

PubMed Central

Chib, Vikram S.; De Martino, Benedetto; Shimojo, Shinsuke; O'Doherty, John P.

2012-01-01

Summary Employers often make payment contingent on performance in order to motivate workers. We used fMRI with a novel incentivized skill task to examine the neural processes underlying behavioral responses to performance-based pay. We found that individuals' performance increased with increasing incentives; however, very high incentive levels led to the paradoxical consequence of worse performance. Between initial incentive presentation and task execution, striatal activity rapidly switched between activation and deactivation in response to increasing incentives. Critically, decrements in performance and striatal deactivations were directly predicted by an independent measure of behavioral loss aversion. These results suggest that incentives associated with successful task performance are initially encoded as a potential gain; however, when actually performing a task, individuals encode the potential loss that would arise from failure. PMID:22578508

Underachievement and the Quest for Dignity

ERIC Educational Resources Information Center

Delisle, Jim

2009-01-01

Here's a statement that might seem the epitome of paradox: Underachievement has little to do with curriculum. Sure, curriculum is the stuff of school, the glue that bonds together one grade level to the next, but when it comes to the so-called underachiever's unwillingness to complete schoolwork and assignments, there is something far greater at…

Building a School Leadership Programme: An American Paradox of Autonomy and Accountability

ERIC Educational Resources Information Center

Reyes-Guerra, Daniel; Russo, Marianne R.; Bogotch, Ira E.; Vásquez-Colina, Maria D.

2014-01-01

School districts within the USA face ever-decreasing autonomy in rendering decisions regarding instruction, curriculum and the leading and managing of schools at the local level due to the ever-increasing accountability measures implemented by district, state and federal governments. This study investigates a joint university-school district…

Education Provision to Nomadic Pastoralists: A Literature Review. IDS Working Paper.

ERIC Educational Resources Information Center

Kratli, Saverio

Educationally, pastoralists appear to be a paradox. From the perspective of official education, they are a complete failure, scoring badly in terms of enrollment, achievement, attainment, and gender balance. However, pastoralists are far from being unskilled. Their daily lives require them to perform tasks involving high levels of individual and…

Evolution and Ontogeny of Stress Response to Social Challenges in the Human Child

ERIC Educational Resources Information Center

Flinn, Mark V.

2006-01-01

The stress response systems of the human child are highly sensitive to social challenges. Because stress hormones can have negative developmental and health consequences, this presents an evolutionary paradox: Why would natural selection have favored mechanisms that elevate stress hormone levels in response to psychosocial stimuli? Two…

Schooling in Mexico: Staying In or Dropping Out.

ERIC Educational Resources Information Center

Martin, Christopher J.

Although a recent Mexican survey found that schooling was the public institution that inspired the most confidence, Mexican government figures for the past decade reveal high dropout rates, particularly at the primary level. This book casts light on this paradox by detailing various social relationships of schooling in two elementary schools in a…

"Macho Men" and Preventive Health Care: Implications for Older Men in Different Social Classes

ERIC Educational Resources Information Center

Springer, Kristen W.; Mouzon, Dawne M.

2011-01-01

The gender paradox in mortality--where men die earlier than women despite having more socioeconomic resources--may be partly explained by men's lower levels of preventive health care. Stereotypical notions of masculinity reduce preventive health care; however, the relationship between masculinity, socioeconomic status (SES), and preventive health…

"Unapologetic and Unafraid": Immigrant Youth Come out from the Shadows

ERIC Educational Resources Information Center

Seif, Hinda

2011-01-01

Young immigrants are challenging the boundaries of citizenship and insisting on their human rights. This chapter examines the civic lives of immigrant youth through the case of Latina/os, exploring the paradox of their apparent low civic education and engagement levels and remarkable participation in recent protests. After an overview of…

Suggestopedia and Soviet Sleep-Learning.

ERIC Educational Resources Information Center

Bancroft, W. Jane

This paper examines the parallels between suggestopedia and Soviet sleep-learning for learning foreign languages. Both systems are based on the idea that the acquisition of information can occur in states below the optimal level of consciousness. Hypnopedia makes use of the period of paradoxical or light sleep that usually occurs just as one is…

Negotiating Subject Hierarchies: Neo-Liberal Influences on the Comprehensive Curriculum of Ireland

ERIC Educational Resources Information Center

Lynch, Raymond; McGarr, Oliver

2016-01-01

This article critically examines the relationship between recent educational policy and the advancement of second-level subject hierarchies in Ireland. The paradox of promoting an individual subject by means of the matriculation system, while also calling for a broad and balanced curriculum, is questioned. The apparent retreat from a commitment to…

Community-Based Prevention Using Simple, Low-Cost, Evidence-Based Kernels and Behavior Vaccines

ERIC Educational Resources Information Center

Embry, Dennis D.

2004-01-01

A paradox exists in community prevention of violence and drugs. Good research now exists on evidence-based programs, yet extensive expenditures on prevention have not produced community-level results. Various multiproblems are quite prevalent in the United States, such as violence, Attention Deficit Hyperactivity Disorder (ADHD), conduct problems,…

LES Is More: (When Evaluating Training)

ERIC Educational Resources Information Center

Ward, Sarah; Parkin, Godfrey; Medsker, Karen

2006-01-01

How paradoxical that evaluation, the main purpose of which is to establish value, often seems to return to the lowest value of anything that people do! Too commonly, in the authors' experience, evaluation is avoided or paid as little attention as possible. Due to its typically unloved nature, evaluation can be trapped in a low-level, minimalist…

The War with Words: Structure and Transcendence. Approaches to Semiotics Series No. 12.

ERIC Educational Resources Information Center

Shands, Harley C.

Semiotic research increasingly reveals the basic importance of structure at all levels of genetic, linguistic, and social process. The paradox that structure not only liberates but also imprisons has been familiar to members of many different cultures, and the search for personal release in transcendent states of feeling contrapuntally illuminates…

Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits

PubMed Central

Acosta-Alvear, Diego; Cho, Min Y; Wild, Thomas; Buchholz, Tonia J; Lerner, Alana G; Simakova, Olga; Hahn, Jamie; Korde, Neha; Landgren, Ola; Maric, Irina; Choudhary, Chunaram; Walter, Peter; Weissman, Jonathan S; Kampmann, Martin

2015-01-01

Hallmarks of cancer, including rapid growth and aneuploidy, can result in non-oncogene addiction to the proteostasis network that can be exploited clinically. The defining example is the exquisite sensitivity of multiple myeloma (MM) to 20S proteasome inhibitors, such as carfilzomib. However, MM patients invariably acquire resistance to these drugs. Using a next-generation shRNA platform, we found that proteostasis factors, including chaperones and stress-response regulators, controlled the response to carfilzomib. Paradoxically, 19S proteasome regulator knockdown induced resistance to carfilzomib in MM and non-MM cells. 19S subunit knockdown did not affect the activity of the 20S subunits targeted by carfilzomib nor their inhibition by the drug, suggesting an alternative mechanism, such as the selective accumulation of protective factors. In MM patients, lower 19S levels predicted a diminished response to carfilzomib-based therapies. Together, our findings suggest that an understanding of network rewiring can inform development of new combination therapies to overcome drug resistance. DOI: http://dx.doi.org/10.7554/eLife.08153.001 PMID:26327694

The Age Prospective Memory Paradox: Young Adults May Not Give Their Best outside of the Lab

ERIC Educational Resources Information Center

Aberle, Ingo; Rendell, Peter G.; Rose, Nathan S.; McDaniel, Mark A.; Kliegel, Matthias

2010-01-01

Previous research has identified the age prospective memory paradox of age-related declines in laboratory settings in contrast to age benefits in naturalistic settings. Various factors are assumed to account for this paradox, yet empirical evidence on this issue is scarce. In 2 experiments, the present study examined the effect of task setting in…

Mathematical background of Parrondo's paradox

NASA Astrophysics Data System (ADS)

Behrends, Ehrhard

2004-05-01

Parrondo's paradox states that there are losing gambling games which, when being combined stochastically or in a suitable deterministic way, give rise to winning games. Here we investigate the probabilistic background. We show how the properties of the equilibrium distributions of the Markov chains under consideration give rise to the paradoxical behavior, and we provide methods how to find the best a priori strategies.

A Mosquito in the Classroom: Using the Cooperative Business Model to Foster Paradoxical Thinking in Management Education

ERIC Educational Resources Information Center

Audebrand, Luc K.; Camus, Annie; Michaud, Valérie

2017-01-01

Although the paradox perspective is gaining increasing attention among management scholars, most of us continue to struggle with addressing this challenging topic in the classroom, as it seems out of reach for many students. In this article, we describe a potentially beneficial way to approach paradoxical thinking in management education: teaching…

A joint analysis of the Drake equation and the Fermi paradox

NASA Astrophysics Data System (ADS)

Prantzos, Nikos

2013-07-01

I propose a unified framework for a joint analysis of the Drake equation and the Fermi paradox, which enables a simultaneous, quantitative study of both of them. The analysis is based on a simplified form of the Drake equation and on a fairly simple scheme for the colonization of the Milky Way. It appears that for sufficiently long-lived civilizations, colonization of the Galaxy is the only reasonable option to gain knowledge about other life forms. This argument allows one to define a region in the parameter space of the Drake equation, where the Fermi paradox definitely holds (`Strong Fermi paradox').

A quantum Rosetta Stone for the information paradox

NASA Astrophysics Data System (ADS)

Pando Zayas, Leopoldo A.

2014-11-01

The black hole information loss paradox epitomizes the contradictions between general relativity and quantum field theory. The AdS/conformal field theory (CFT) correspondence provides an implicit answer for the information loss paradox in black hole physics by equating a gravity theory with an explicitly unitary field theory. Gravitational collapse in asymptotically AdS spacetimes is generically turbulent. Given that the mechanism to read out the information about correlations functions in the field theory side is plagued by deterministic classical chaos, we argue that quantum chaos might provide the true Rosetta Stone for answering the information paradox in the context of the AdS/CFT correspondence.

A Comparative Study of Iron Uptake Mechanisms in Marine Microalgae: Iron Binding at the Cell Surface Is a Critical Step1[W][OA

PubMed Central

Sutak, Robert; Botebol, Hugo; Blaiseau, Pierre-Louis; Léger, Thibaut; Bouget, François-Yves; Camadro, Jean-Michel; Lesuisse, Emmanuel

2012-01-01

We investigated iron uptake mechanisms in five marine microalgae from different ecologically important phyla: the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana, the prasinophyceae Ostreococcus tauri and Micromonas pusilla, and the coccolithophore Emiliania huxleyi. Among these species, only the two diatoms were clearly able to reduce iron, via an inducible (P. tricornutum) or constitutive (T. pseudonana) ferrireductase system displaying characteristics similar to the yeast (Saccharomyces cerevisiae) flavohemoproteins proteins. Iron uptake mechanisms probably involve very different components according to the species, but the species we studied shared common features. Regardless of the presence and/or induction of a ferrireductase system, all the species were able to take up both ferric and ferrous iron, and iron reduction was not a prerequisite for uptake. Iron uptake decreased with increasing the affinity constants of iron-ligand complexes and with increasing ligand-iron ratios. Therefore, at least one step of the iron uptake mechanism involves a thermodynamically controlled process. Another step escapes to simple thermodynamic rules and involves specific and strong binding of ferric as well as ferrous iron at the cell surface before uptake of iron. Binding was paradoxically increased in iron-rich conditions, whereas uptake per se was induced in all species only after prolonged iron deprivation. We sought cell proteins loaded with iron following iron uptake. One such protein in O. tauri may be ferritin, and in P. tricornutum, Isip1 may be involved. We conclude that the species we studied have uptake systems for both ferric and ferrous iron, both involving specific iron binding at the cell surface. PMID:23033141

Substrate-Induced Facilitated Dissociation of the Competitive Inhibitor from the Active Site of O-Acetyl Serine Sulfhydrylase Reveals a Competitive-Allostery Mechanism.

PubMed

Singh, Appu Kumar; Ekka, Mary Krishna; Kaushik, Abhishek; Pandya, Vaibhav; Singh, Ravi P; Banerjee, Shrijita; Mittal, Monica; Singh, Vijay; Kumaran, S

2017-09-19

By classical competitive antagonism, a substrate and competitive inhibitor must bind mutually exclusively to the active site. The competitive inhibition of O-acetyl serine sulfhydrylase (OASS) by the C-terminus of serine acetyltransferase (SAT) presents a paradox, because the C-terminus of SAT binds to the active site of OASS with an affinity that is 4-6 log-fold (10 4 -10 6 ) greater than that of the substrate. Therefore, we employed multiple approaches to understand how the substrate gains access to the OASS active site under physiological conditions. Single-molecule and ensemble approaches showed that the active site-bound high-affinity competitive inhibitor is actively dissociated by the substrate, which is not consistent with classical views of competitive antagonism. We employed fast-flow kinetic approaches to demonstrate that substrate-mediated dissociation of full length SAT-OASS (cysteine regulatory complex) follows a noncanonical "facilitated dissociation" mechanism. To understand the mechanism by which the substrate induces inhibitor dissociation, we resolved the crystal structures of enzyme·inhibitor·substrate ternary complexes. Crystal structures reveal a competitive allosteric binding mechanism in which the substrate intrudes into the inhibitor-bound active site and disengages the inhibitor before occupying the site vacated by the inhibitor. In summary, here we reveal a new type of competitive allosteric binding mechanism by which one of the competitive antagonists facilitates the dissociation of the other. Together, our results indicate that "competitive allostery" is the general feature of noncanonical "facilitated/accelerated dissociation" mechanisms. Further understanding of the mechanistic framework of "competitive allosteric" mechanism may allow us to design a new family of "competitive allosteric drugs/small molecules" that will have improved selectivity and specificity as compared to their competitive and allosteric counterparts.

Changes in /sup 3/H-substance P receptor binding in the rat brain after kainic acid lesion of the corpus striatum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mantyh, P.W.; Hunt, S.P.

1986-06-01

Previous studies have indicated that the substantia nigra contains the highest concentration of substance P-like immunoreactivity (SPLI) in the brain. Paradoxically, it also appears to contain one of the lowest concentrations of substance P receptors in the brain. One possibility is that the massive amount of SPLI blocks the binding of the radioligand to the substance P receptor and/or down-regulates the number of substance P receptors present in this structure. Since greater than 95% of the SPLI within the substantia nigra originates from the corpus striatum, we have lesioned this area and measured the changes in substance P receptor concentrationmore » in the substantia nigra and other corpus striatal projection areas. A semiquantitative autoradiographic technique for measuring the binding of /sup 3/H-substance P to substance P receptors was used in conjunction with tritium-sensitive film. 3H-substance P binding was measured in both the corpus striatum and its projection areas after kainic acid lesion of the corpus striatum. At either 4 or 21 d after the lesion there was approximately a 90% loss of substance P receptors in the rostral striatum, a 74% loss in the globus pallidus, a 57% increase in receptor number in lamina I and II of the ipsilateral somatosensory cortex, and no apparent change in the number of receptors in the substantia nigra pars reticulata, superior colliculus, and central gray. These findings suggest that the low concentration of substance P receptors found within the substantia nigra is not due the massive SPLI innervation, since removal of greater than 95% of the SPLI had no measurable effect on the concentration of substance P receptors.« less

Stable coordination of the inhibitory Ca2+ ion at MIDAS in integrin CD11b/CD18 by an antibody-derived ligand aspartate: Implications for integrin regulation and structure-based drug design

PubMed Central

Mahalingam, Bhuvaneshwari; Ajroud, Kaouther; Alonso, Jose Luis; Anand, Saurabh; Adair, Brian; Horenstein, Alberto L; Malavasi, Fabio; Xiong, Jian-Ping; Arnaout, M. Amin

2011-01-01

A central feature of integrin interaction with physiologic ligands is the monodentate binding of a ligand carboxylate to a Mg2+ ion hexacoordinated at the metal-ion-dependent-adhesion site (MIDAS) in the integrin A-domain. This interaction stabilizes the A-domain in the high-affinity state, which is distinguished from the default low-affinity state by tertiary changes in the domain that culminate in cell adhesion. Small molecule ligand-mimetic integrin antagonists act as partial agonists, eliciting similar activating conformational changes in the A-domain, which has contributed to paradoxical adhesion and increased patient mortality in large clinical trials. As with other ligand-mimetic integrin antagonists, the function-blocking monoclonal antibody (mAb) 107 binds MIDAS of integrin CD11b/CD18 A-domain (CD11bA), but in contrast, it favors the inhibitory Ca2+ ion over Mg2+ at MIDAS. We determined the crystal structures of the Fab fragment of mAb 107 complexed to the low- and high-affinity states of CD11bA. Favored binding of Ca2+ at MIDAS is caused by the unusual symmetric bidentate ligation of a Fab-derived ligand Asp to a heptacoordinated MIDAS Ca2+. Binding of Fab 107 to CD11bA did not trigger the activating tertiary changes in the domain or in the full-length integrin. These data show that denticity of the ligand Asp/Glu can modify divalent cation selectivity at MIDAS and hence integrin function. Stabilizing the Ca2+ ion at MIDAS by bidentate ligation to a ligand Asp/Glu may provide one approach for designing pure integrin antagonists. PMID:22095715

Paradoxical anaerobism in desert pupfish.

PubMed

Heuton, Matt; Ayala, Luis; Burg, Chris; Dayton, Kyle; McKenna, Ken; Morante, Aldo; Puentedura, Georgina; Urbina, Natasha; Hillyard, Stanley; Steinberg, Spencer; van Breukelen, Frank

2015-12-01

In order to estimate metabolic demands of desert pupfish for conservation purposes, we measured oxygen consumption in fish acclimated to the ecologically relevant temperatures of 28 or 33°C. For these experiments, we used fish derived from a refuge population of Devils Hole pupfish (Cyprinodon diabolis). Measurement of routine oxygen consumption (V̇O2,routine) revealed some 33°C-acclimated fish (10% of 295 assayed fish) periodically exhibited periods of no measurable oxygen consumption despite available ambient oxygen tensions that were above the critical PO2. We call this phenomenon paradoxical anaerobism. The longest observed continuous bout with no oxygen consumption was 149 min, although typical bouts were much shorter. Fish maintained normal posture and ventilation rate (>230 ventilations per minute) during paradoxical anaerobism. Fish rarely demonstrated a compensatory increase in oxygen use following a period of paradoxical anaerobism. In contrast, only one out of 262 sampled fish acclimated at 28°C spontaneously demonstrated paradoxical anaerobism. Muscle lactate concentration was not elevated during periods of paradoxical anaerobism. However, the amount of ethanol released by the 33°C-acclimated fish was 7.3 times greater than that released by the 28°C acclimation group, suggesting ethanol may be used as an alternative end product of anaerobic metabolism. Exposure to exogenous ethanol, in concentrations as low as 0.1%, produced periods of paradoxical anaerobism even in 28°C-acclimated fish. © 2015. Published by The Company of Biologists Ltd.

Obesity Paradox in End-Stage Kidney Disease Patients

PubMed Central

Park, Jongha; Ahmadi, Seyed-Foad; Streja, Elani; Molnar, Miklos Z; Flegal, Katherine M.; Gillen, Daniel; Kovesdy, Csaba P.; Kalantar-Zadeh, Kamyar

2016-01-01

In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients with end-stage renal disease (ESRD), however, an “obesity paradox” or “reverse epidemiology” (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients.. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients. PMID:24438733

A Note on Explaining Away and Paradoxical Results in Multidimensional Item Response Theory. Research Report. ETS RR-12-13

ERIC Educational Resources Information Center

van Rijn, Peter W.; Rijmen, Frank

2012-01-01

Hooker and colleagues addressed a paradoxical situation that can arise in the application of multidimensional item response theory (MIRT) models to educational test data. We demonstrate that this MIRT paradox is an instance of the explaining-away phenomenon in Bayesian networks, and we attempt to enhance the understanding of MIRT models by placing…

Paradoxical vestibular syndrome in a dog from western Newfoundland infected with French heartworm (Angiostrongylus vasorum)

PubMed Central

Jang, Hye-Yeon; Parent, Joane M.; Hagen, Chris; Colwell, Emily; Rist, Paul M.; Murphy, Nicole; Burton, Shelley; Conboy, Gary

2016-01-01

A dog from western Newfoundland was presented with paradoxical vestibular syndrome. First-stage larvae of Angiostrongylus vasorum were detected on fecal examination. Treatment with milbemycin oxime resulted in resolution of signs. This is the first report of the spread of this parasite to western Newfoundland and of paradoxical vestibular syndrome in a dog infected with A. vasorum. PMID:27928171

Can Virtue Be Taught and How? Confucius on the Paradox of Moral Education

ERIC Educational Resources Information Center

Huang, Yong

2011-01-01

In this paper I shall first examine an apparent paradox in Confucius' view on whether everyone is perfectible through education: on the one hand, he states that education should be provided to all, on the other hand, he says that common people cannot be made to know things. To understand this apparent paradox, I shall argue that education for…

Obesity paradox in patients undergoing coronary intervention: A review

PubMed Central

Patel, Nirav; Elsaid, Ossama; Shenoy, Abhishek; Sharma, Abhishek; McFarlane, Samy I

2017-01-01

There is strong relationship exist between obesity and cardiovascular disease including coronary artery disease (CAD). However, better outcomes noted in obese patients undergoing percutaneous cardiovascular interventions for CAD, a phenomenon known as the obesity paradox. In this review, we performed extensive search for obesity paradox in obese patients undergoing percutaneous coronary intervention and discussed possible mechanism and disparities in different race and sex. PMID:29081905

Policy commercializing nonprofits in health: the history of a paradox from the 19th century to the ACA.

PubMed

Fox, Daniel M

2015-03-01

POLICY POINTS: Health policy in the United States has, for more than a century, simultaneously and paradoxically incentivized the growth as well as the commercialization of nonprofit organizations in the health sector. This policy paradox persists during the implementation of the Affordable Care Act of 2010. For more than a century, policy in the United States has incentivized both expansion in the number and size of tax-exempt nonprofit organizations in the health sector and their commercialization. The implementation of the Affordable Care Act of 2010 (ACA) began yet another chapter in the history of this policy paradox. This article explores the origin and persistence of the paradox using what many scholars call "interpretive social science." This methodology prioritizes history and contingency over formal theory and methods in order to present coherent and plausible narratives of events and explanations for them. These narratives are grounded in documents generated by participants in particular events, as well as conversations with them, observing them in action, and analysis of pertinent secondary sources. The methodology achieves validity and reliability by gathering information from multiple sources and making disciplined judgments about its coherence and correspondence with reality. A paradox with deep historical roots persists as a result of consensus about its value for both population health and the revenue of individuals and organizations in the health sector. Participants in this consensus include leaders of governance who have disagreed about many other issues. The paradox persists because of assumptions about the burden of disease and how to address it, as well as about the effects of biomedical science that is translated into professional education, practice, and the organization of services for the prevention, diagnosis, treatment, and management of illness. The policy paradox that has incentivized the growth and commercialization of nonprofits in the health sector since the late 19th century remains influential in health policy, especially for the allocation of resources. However, aspects of the implementation of the ACA may constrain some of the effects of the paradox. © 2015 Milbank Memorial Fund.

Policy Commercializing Nonprofits in Health: The History of a Paradox From the 19th Century to the ACA

PubMed Central

FOX, DANIEL M

2015-01-01

Policy Points: Health policy in the United States has, for more than a century, simultaneously and paradoxically incentivized the growth as well as the commercialization of nonprofit organizations in the health sector. This policy paradox persists during the implementation of the Affordable Care Act of 2010. Context For more than a century, policy in the United States has incentivized both expansion in the number and size of tax-exempt nonprofit organizations in the health sector and their commercialization. The implementation of the Affordable Care Act of 2010 (ACA) began yet another chapter in the history of this policy paradox. Methods This article explores the origin and persistence of the paradox using what many scholars call “interpretive social science.” This methodology prioritizes history and contingency over formal theory and methods in order to present coherent and plausible narratives of events and explanations for them. These narratives are grounded in documents generated by participants in particular events, as well as conversations with them, observing them in action, and analysis of pertinent secondary sources. The methodology achieves validity and reliability by gathering information from multiple sources and making disciplined judgments about its coherence and correspondence with reality. Findings A paradox with deep historical roots persists as a result of consensus about its value for both population health and the revenue of individuals and organizations in the health sector. Participants in this consensus include leaders of governance who have disagreed about many other issues. The paradox persists because of assumptions about the burden of disease and how to address it, as well as about the effects of biomedical science that is translated into professional education, practice, and the organization of services for the prevention, diagnosis, treatment, and management of illness. Conclusions The policy paradox that has incentivized the growth and commercialization of nonprofits in the health sector since the late 19th century remains influential in health policy, especially for the allocation of resources. However, aspects of the implementation of the ACA may constrain some of the effects of the paradox. PMID:25752354

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Jun-Ho; Ahn, Soon Kil; YOUAI Co., Ltd., Suwon-Si, Gyeonggi-Do 443-766

Highlights: Black-Right-Pointing-Pointer We recently discovered a potent and selective B-Raf inhibitor, UI-152. Black-Right-Pointing-Pointer UI-152 displayed a selective cytotoxicity toward v-Ha-ras transformed cells. Black-Right-Pointing-Pointer UI-152-induced growth inhibition was largely meditated by autophagy. Black-Right-Pointing-Pointer UI-152 induced paradoxical activation of Raf-1. -- Abstract: In human cancers, B-Raf is the most frequently mutated protein kinase in the MAPK signaling cascade, making it an important therapeutic target. We recently discovered a potent and selective B-Raf inhibitor, UI-152, by using a structure-based drug design strategy. In this study, we examined whether B-Raf inhibition by UI-152 may be an effective therapeutic strategy for eliminating cancer cells transformedmore » with v-Ha-ras (Ras-NIH 3T3). UI-152 displayed selective cytotoxicity toward Ras-NIH 3T3 cells while having little to no effect on non-transformed NIH 3T3 cells. We found that treatment with UI-152 markedly increased autophagy and, to a lesser extent, apoptosis. However, inhibition of autophagy by addition of 3-MA failed to reverse the cytotoxic effects of UI-152 on Ras-NIH 3T3 cells, demonstrating that apoptosis and autophagy can act as cooperative partners to induce growth inhibition in Ras-NIH 3T3 cells treated with UI-152. Most interestingly, cell responses to UI-152 appear to be paradoxical. Here, we showed that although UI-152 inhibited ERK, it induced B-Raf binding to Raf-1 as well as Raf-1 activation. This paradoxical activation of Raf-1 by UI-152 is likely to be coupled with the inhibition of the mTOR pathway, an intracellular signaling pathway involved in autophagy. We also showed for the first time that, in multi-drug resistant cells, the combination of UI-152 with verapamil significantly decreased cell proliferation and increased autophagy. Thus, our findings suggest that the inhibition of autophagy, in combination with UI-152, offers a more effective therapeutic strategy for v-Ha-ras-transformed cells harboring wild-type B-Raf.« less

Not a Simple Tether: Binding of Toxoplasma gondii AMA1 to RON2 during Invasion Protects AMA1 from Rhomboid-Mediated Cleavage and Leads to Dephosphorylation of Its Cytosolic Tail

PubMed Central

Krishnamurthy, Shruthi; Deng, Bin; del Rio, Roxana; Buchholz, Kerry R.; Treeck, Moritz; Urban, Siniša; Boothroyd, John; Lam, Ying-Wai

2016-01-01

ABSTRACT Apical membrane antigen 1 (AMA1) is a receptor protein on the surface of Toxoplasma gondii that plays a critical role in host cell invasion. The ligand to which T. gondii AMA1 (TgAMA1) binds, TgRON2, is secreted into the host cell membrane by the parasite during the early stages of invasion. The TgAMA1-TgRON2 complex forms the core of the “moving junction,” a ring-shaped zone of tight contact between the parasite and host cell membranes, through which the parasite pushes itself during invasion. Paradoxically, the parasite also expresses rhomboid proteases that constitutively cleave the TgAMA1 transmembrane domain. How can TgAMA1 function effectively in host cell binding if its extracellular domain is constantly shed from the parasite surface? We show here that when TgAMA1 binds the domain 3 (D3) peptide of TgRON2, its susceptibility to cleavage by rhomboid protease(s) is greatly reduced. This likely serves to maintain parasite-host cell binding at the moving junction, a hypothesis supported by data showing that parasites expressing a hypercleavable version of TgAMA1 invade less efficiently than wild-type parasites do. Treatment of parasites with the D3 peptide was also found to reduce phosphorylation of S527 on the cytoplasmic tail of TgAMA1, and parasites expressing a phosphomimetic S527D allele of TgAMA1 showed an invasion defect. Taken together, these data suggest that TgAMA1-TgRON2 interaction at the moving junction protects TgAMA1 molecules that are actively engaged in host cell penetration from rhomboid-mediated cleavage and generates an outside-in signal that leads to dephosphorylation of the TgAMA1 cytosolic tail. Both of these effects are required for maximally efficient host cell invasion. PMID:27624124

Professional paradox: identity formation in qualified doctors pursuing further training.

PubMed

Chan, Mercedes; Pratt, Dan; Poole, Gary; Sidhu, Ravi

2018-03-01

Many newly qualified specialists and subspecialists pursue additional training. Although their motivations are many, the pursuit of further training as an alternative to unemployment is an emerging trend. Paradoxically, doctors continue as trainees with a consultant's credentials, and without the guarantee of eventual employment. This study explores seven doctors' experiences, the effects of further training on their professional identity formation (PIF), and how these effects are reconciled on a personal and professional level. This phenomenological study involved interviews with seven qualified Canadian specialists (three were female) who pursued additional training in response to a lack of available positions in their respective specialties. Template analysis generated theoretical constructs of influences on their PIF, and characteristics of their lived experiences. Four themes shaped PIF: setting and context; language and communication; responsibilities and privileges; and participants' visions of their future selves. Professional identity formation (PIF) continued to develop in further training, but was inconsistently affirmed by participants' communities of practice. Four major themes characterised training experiences: prescription; managing multiple masters; limiting access to others and community ties; and constantly questioning the value of extra training. Qualified doctors traverse professional paradoxes as they seek further education with no guarantee of employment and provide consultant-level care as 'trainees'. An identity dissonance emerges that may continue until a clear identity is prescribed for them. Although disruptive to these doctors' PIF and personal and professional lives, the long-term effects of additional training are unknown. Its utility and influence on securing employment and future job satisfaction are areas for further research. © 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Experimental test of the irreducible four-qubit Greenberger-Horne-Zeilinger paradox

NASA Astrophysics Data System (ADS)

Su, Zu-En; Tang, Wei-Dong; Wu, Dian; Cai, Xin-Dong; Yang, Tao; Li, Li; Liu, Nai-Le; Lu, Chao-Yang; Żukowski, Marek; Pan, Jian-Wei

2017-03-01

The paradox of Greenberger-Horne-Zeilinger (GHZ) disproves directly the concept of EPR elements of reality, based on the EPR correlations, in an all-versus-nothing way. A three-qubit experimental demonstration of the GHZ paradox was achieved nearly 20 years ago, followed by demonstrations for more qubits. Still, the GHZ contradictions underlying the tests can be reduced to a three-qubit one. We show an irreducible four-qubit GHZ paradox, and report its experimental demonstration. The bound of a three-setting-per-party Bell-GHZ inequality is violated by 7 σ . The fidelity of the GHZ state was around 81 % , and an entanglement witness reveals a violation of the separability threshold by 19 σ .

The Paradox of Discrimination, the “Aloha Spirit,” and Symptoms of Depression in Hawai‘i

PubMed Central

Wongkaren, Turro S

2016-01-01

It remains to be determined whether the “aloha spirit” is a cultural resource that influences psychological well-being in Hawai‘i. Thus, the purpose of this study is to investigate whether the aloha spirit is associated with levels of psychological distress and the risk of depression, while taking into account various risk factors. Data for this study were drawn from an anonymous survey of undergraduate students (N = 1,028) at the University of Hawai‘i. Regression results revealed that having learned the aloha spirit was associated with significantly lower levels (b = −1.76; P < .01) of psychological distress and a reduced odds of depression (OR = .69; P < .01) over and above the effects of perceived discrimination, local identity, levels of ethnic identification, race/ethnicity, immigrant status, duration of residence in Hawai‘i, and other sociodemographic factors. In contrast, everyday discrimination was associated with significantly higher levels (b = 0.41; P < .001) of psychological distress and a greater odds of depression (OR = 1.08; P < .001). Together, these findings highlight the paradox of discrimination and the aloha spirit in Hawai‘i by documenting their distinct relationships with mental health. Overall, this study contributes to medical and public health research on mental health disparities during the transition to adulthood by delving into the social context of daily life in the understudied, multicultural location of Hawai‘i. PMID:26870601

The Paradox of Discrimination, the "Aloha Spirit," and Symptoms of Depression in Hawai'i.

PubMed

Mossakowski, Krysia N; Wongkaren, Turro S

2016-01-01

It remains to be determined whether the "aloha spirit" is a cultural resource that influences psychological well-being in Hawai'i. Thus, the purpose of this study is to investigate whether the aloha spirit is associated with levels of psychological distress and the risk of depression, while taking into account various risk factors. Data for this study were drawn from an anonymous survey of undergraduate students (N = 1,028) at the University of Hawai'i. Regression results revealed that having learned the aloha spirit was associated with significantly lower levels (b = -1.76; P < .01) of psychological distress and a reduced odds of depression (OR = .69; P < .01) over and above the effects of perceived discrimination, local identity, levels of ethnic identification, race/ethnicity, immigrant status, duration of residence in Hawai'i, and other sociodemographic factors. In contrast, everyday discrimination was associated with significantly higher levels (b = 0.41; P < .001) of psychological distress and a greater odds of depression (OR = 1.08; P < .001). Together, these findings highlight the paradox of discrimination and the aloha spirit in Hawai'i by documenting their distinct relationships with mental health. Overall, this study contributes to medical and public health research on mental health disparities during the transition to adulthood by delving into the social context of daily life in the understudied, multicultural location of Hawai'i.

Nomadic-colonial life strategies enable paradoxical survival and growth despite habitat destruction

PubMed Central

Tan, Zong Xuan; Cheong, Kang Hao

2017-01-01

Organisms often exhibit behavioral or phenotypic diversity to improve population fitness in the face of environmental variability. When each behavior or phenotype is individually maladaptive, alternating between these losing strategies can counter-intuitively result in population persistence–an outcome similar to the Parrondo’s paradox. Instead of the capital or history dependence that characterize traditional Parrondo games, most ecological models which exhibit such paradoxical behavior depend on the presence of exogenous environmental variation. Here we present a population model that exhibits Parrondo’s paradox through capital and history-dependent dynamics. Two sub-populations comprise our model: nomads, who live independently without competition or cooperation, and colonists, who engage in competition, cooperation, and long-term habitat destruction. Nomads and colonists may alternate behaviors in response to changes in the colonial habitat. Even when nomadism and colonialism individually lead to extinction, switching between these strategies at the appropriate moments can paradoxically enable both population persistence and long-term growth. DOI: http://dx.doi.org/10.7554/eLife.21673.001 PMID:28084993

[A case of tuberculous liver abscess developed during chemotherapy for tuberculous peritonitis as paradoxical response].

PubMed

Kim, Tae Kyung; Choi, Cheol Woong; Ha, Jong Kun; Jang, Hyung Ha; Park, Su Bum; Kim, Hyung Wook; Kang, Dae Hwan

2013-07-01

Tuberculous liver abscesses are rare. Paradoxical response in tuberculosis is common and occurred between 2 weeks and 12 weeks after anti-tuberculous medication. We report here a case of tuberculous liver abscess that developed in a paradoxical response during chemotherapy for tuberculous peritonitis in a 23-year-old male. He was hospitalized, complaining of ascites, epigastric pain. He was diagnosed tuberculous peritonitis by expiratory laparoscopic biopsy and took medication for tuberculosis. After 2 months, a hepatic lesion was detected with CT scan incidentally. Chronic granulomatous inflammation was seen in ultrasound-guided liver biopsy, and tuberculous liver abscess was diagnosed. It was considered as paradoxical response, rather than treatment failure or other else because clinical symptoms of peritoneal tuberculosis and CT scan improved. After continuing initial anti-tuberculous medication, he was successfully treated. Herein, we report a case of tuberculous liver abscess as paradoxical response while treating peritoneal tuberculosis without changing anti-tuberculous treatment regimen.

Obesity and the obesity paradox in heart failure.

PubMed

Gupta, Pritha P; Fonarow, Gregg C; Horwich, Tamara B

2015-02-01

Obesity has reached epidemic proportions in the general population and is associated with an increased risk for the development of new-onset heart failure (HF). However, in acute and chronic HF, overweight and mild to moderate obesity is associated with substantially improved survival compared with normal weight. This phenomenon has been termed the "obesity paradox" in HF. The majority of data pertaining to the obesity paradox identifies obesity with body mass index; however, the reliability of this method has been questioned. Newer studies have explored the use of other measures of body fat and body composition, including waist circumference, waist-to-hip ratio, skinfold thickness, and bioelectrical impedance analysis of body composition. The relationship between the obesity paradox and cardiorespiratory fitness in HF is also discussed in this review, and we explore the various potential explanations for the obesity paradox and summarize the current evidence and guidelines for intentional weight loss treatments for HF in the obese population. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Revisiting the 'Low BirthWeight paradox' using a model-based definition.

PubMed

Juárez, Sol; Ploubidis, George B; Clarke, Lynda

2014-01-01

Immigrant mothers in Spain have a lower risk of delivering Low BirthWeight (LBW) babies in comparison to Spaniards (LBW paradox). This study aimed at revisiting this finding by applying a model-based threshold as an alternative to the conventional definition of LBW. Vital information data from Madrid was used (2005-2006). LBW was defined in two ways (less than 2500g and Wilcox's proposal). Logistic and linear regression models were run. According to common definition of LBW (less than 2500g) there is evidence to support the LBW paradox in Spain. Nevertheless, when an alternative model-based definition of LBW is used, the paradox is only clearly present in mothers from the rest of Southern America, suggesting a possible methodological bias effect. In the future, any examination of the existence of the LBW paradox should incorporate model-based definitions of LBW in order to avoid methodological bias. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Paradoxical skin lesions induced by anti-TNF-α agents in SAPHO syndrome.

PubMed

Li, Chen; Wu, Xia; Cao, Yihan; Zeng, Yueping; Zhang, Weihong; Zhang, Shuo; Liu, Yuehua; Jin, Hongzhong; Zhang, Wen; Li, Li

2018-04-03

The objectives of the study were to characterize the clinical picture of paradoxical skin lesions in SAPHO patients treated with anti-TNF-α agents and to explore its pathogenesis. Patients treated with anti-TNF-α therapy were identified from a cohort of 164 SAPHO patients. The clinical data and skin biopsies were collected. The usage, efficacy, and side effects of anti-TNF-α therapy were recorded. Forty-one (25.0%) patients received anti-TNF-α therapy, of which seven (17.1%) developed paradoxical skin lesions after 1 to 14 infusions. Patients with such lesions were older at onset of skin lesions than those without (p = 0.034). Expression of TNF-α in palmoplantar pustulosis increased after anti-TNF-α therapy in the two examined patients with exacerbated skin lesions. Anti-TNF-α therapy induces paradoxical skin lesions in 17.1% SAPHO patients. Late onset of skin manifestations is associated with an increased risk of such lesions. The paradoxical elevation of TNF-α expression in lesions may contribute to this phenomenon.

Scrounging by foragers can resolve the paradox of enrichment

PubMed Central

2017-01-01

Theoretical models of predator–prey systems predict that sufficient enrichment of prey can generate large amplitude limit cycles, paradoxically causing a high risk of extinction (the paradox of enrichment). Although real ecological communities contain many gregarious species, whose foraging behaviour should be influenced by socially transmitted information, few theoretical studies have examined the possibility that social foraging might resolve this paradox. I considered a predator population in which individuals play the producer–scrounger foraging game in one-prey-one-predator and two-prey-one-predator systems. I analysed the stability of a coexisting equilibrium point in the one-prey system and that of non-equilibrium dynamics in the two-prey system. The results revealed that social foraging could stabilize both systems, and thereby resolve the paradox of enrichment when scrounging behaviour (i.e. kleptoparasitism) is prevalent in predators. This suggests a previously neglected mechanism underlying a powerful effect of group-living animals on the sustainability of ecological communities. PMID:28405371

Paradoxical Cerebral Fat Embolism in Revision Hip Surgery

PubMed Central

Piuzzi, Nicolás S.; Zanotti, Gerardo; Comba, Fernando M.; Buttaro, Martin A.; Piccaluga, Francisco

2014-01-01

The incidence of clinical fat embolism syndrome (FES) is low (<1%) whilst fat embolism (FE) of marrow fat appears to occur more often (Mellor and Soni (2001)). Paradoxical brain FE may occur in patients undergoing hip orthopedic surgery who have an undocumented patent foramen ovale (PFO). We report a case of an eighty-year-old male patient, who underwent a scheduled revision hip surgery suffering a paradoxical cerebral FE. PMID:25184065

A Computational Model for Observation in Quantum Mechanics.

DTIC Science & Technology

1987-03-16

Interferometer experiment ............. 17 2.3 The EPR Paradox experiment ................. 22 3 The Computational Model, an Overview 28 4 Implementation 34...40 4.4 Code for the EPR paradox experiment ............... 46 4.5 Code for the double slit interferometer experiment ..... .. 50 5 Conclusions 59 A...particle run counter to fact. The EPR paradox experiment (see section 2.3) is hard to resolve with this class of models, collectively called hidden

Brownian motion and gambling: from ratchets to paradoxical games

NASA Astrophysics Data System (ADS)

Parrondo, J. M. R.; Dinís, Luis

2004-02-01

Two losing gambling games, when alternated in a periodic or random fashion, can produce a winning game. This paradox has been inspired by certain physical systems capable of rectifying fluctuations: the so-called Brownian ratchets. In this paper we review this paradox, from Brownian ratchets to the most recent studies on collective games, providing some intuitive explanations of the unexpected phenomena that we will find along the way.

An experimental study of the Online Information Paradox: Does en-route information improve road network performance?

PubMed

Wijayaratna, Kasun P; Dixit, Vinayak V; Denant-Boemont, Laurent; Waller, S Travis

2017-01-01

This study investigates the empirical presence of a theoretical transportation paradox, defined as the "Online Information Paradox" (OIP). The paradox suggests that, for certain road networks, the provision of online information deteriorate travel conditions for all users of that network relative to the situation where no online information is provided to users. The analytical presence of the paradox was derived for a specific network structure by using two equilibrium models, the first being the Expected User Equilibrium (EUE) solution (no information scenario) and the other being the User Equilibrium with Recourse (UER) solution (with information scenario). An incentivised computerised route choice game was designed using the concepts of experimental economics and administered in a controlled laboratory environment to investigate the physical presence of the paradox. Aggregate statistics of path flows and Total System Travel Costs (TSTC) were used to compare the experimental results with the theoretical findings. A total of 12 groups of 12 participants completed the experiment and the OIP and the occurrence of the OIP being significant was observed in 11 of the 12 cases. Though information increased travel costs for users on average, it reduced the volatility of travel costs experienced in the no information scenario indicating that information can achieve a more reliable system. Further replications of similar experiments and more importantly field based identification of the phenomena will force transport professionals to be aware of the emergence of the paradox. In addition, studies such as this emphasise the need for the adoption of adaptive traffic assignment techniques to appropriately model the acquisition of information on a road network.

Evaluation of seismic reflection data in the Davis and Lavender Canyons study area, Paradox Basin, Utah. [Faults, folds, joints, and collapse structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitcho, C.A.; Wong, I.G.; Turcotte, F.T.

1986-08-01

Seismic reflection data purchased from petroleum industry brokers and acquired through group speculative surveys were interpreted for information on the regional subsurface geologic structure and stratigraphy within and surrounding the Davis and Lavender Canyons study area in the Paradox Basin of southeastern Utah. Structures of interest were faults, folds, joints, and collapse structures related to salt dissolution. The seismic reflection data were used to interpret stratigraphy by identifying continuous and discontinuous reflectors on the seismic profiles. Thickening and thinning of strata and possible areas of salt flowage or dissolution could be identified from the seismic data. Identifiable reflectors included themore » tops of the Precambrian and Mississippian, a distinctive interbed close to the middle of the Pennsylvanian Paradox salt formation (probably the interval between Salt Cycles 10 and 13), and near the top of the Paradox salt. Of the 56 faults identified from the seismic reflection interpretation, 33 trend northwest, west-northwest, or west, and most affect only the deeper part of the stratigraphic section. These faults are part of the deep structural system found throughout the Paradox Basin, including the fold and fault belt in the northeast part of the basin. The faults bound basement Precambrian blocks that experienced minor activity during Mississippian and early Pennsylvanian deposition, and showed major displacement during early Paradox salt deposition as the Paradox Basin subsided. Based on the seismic data, most of these faults appear to have an upward terminus between the top of the Mississippian and the salt interbed reflector.« less

Social Comparison and Confidence: When Thinking You're Better than Average Predicts Overconfidence (And when It Does Not)

ERIC Educational Resources Information Center

Larrick, Richard P.; Burson, Katherine A.; Soll, Jack B.

2007-01-01

A common social comparison bias--the better-than-average-effect--is frequently described as psychologically equivalent to the individual-level judgment bias known as overconfidence. However, research has found "Hard-easy" effects for each bias that yield a seemingly paradoxical reversal: Hard tasks tend to produce overconfidence but…

A Paradox in Physics Education in France

ERIC Educational Resources Information Center

Smigiel, Eddie; Sonntag, Michel

2013-01-01

This paper deals with the nature and the level of difficulty of teaching and learning physics in the first year of undergraduate engineering schools in France. Our case study is based on a survey regarding a classic and basic question in applied physics, and which was conducted with a group of second-year students in a post-baccalaureate 1…

Promise and Paradox: Measuring Students' Non-Cognitive Skills and the Impact of Schooling

ERIC Educational Resources Information Center

West, Martin R.; Kraft, Matthew A.; Finn, Amy S.; Martin, Rebecca E.; Duckworth, Angela L.; Gabrieli, Christopher F. O.; Gabrieli, John D. E.

2016-01-01

We used self-report surveys to gather information on a broad set of non-cognitive skills from 1,368 eighth graders. At the student level, scales measuring conscientiousness, self-control, grit, and growth mindset are positively correlated with attendance, behavior, and test-score gains between fourth grade and eighth grade. Conscientiousness,…

Cybernetic Serendipity: Behind the Paradox of Machine Assisted Art Lies a Boundless World of Creativity.

ERIC Educational Resources Information Center

Peterson, Dale

1984-01-01

Discusses the works of Darcy Gerbarg, Ruth Leavitt, David Em, Duane Palyka, and Harold Cohen, visual artists who work with computers to create art works by relying on standard hardware/software tools, using custom tools created for nonartistic tasks, manipulating images at the programing level, and programing creativity into computers themselves.…

First-Year College Student Affect and Alcohol Use: Paradoxical within-and between-Person Associations

ERIC Educational Resources Information Center

Rankin, Lela A.; Maggs, Jennifer L.

2006-01-01

Based on 10 weekly telephone interviews with first-year college students (N=202; 63% women; M=18.8 years, SD=0.4), within- and between-person associations of positive and negative affect with alcohol use were examined. Multi-level models confirmed hypothesized within-person associations between weekly positive affect and alcohol use: Higher…

Quantum Hilbert Hotel.

PubMed

Potoček, Václav; Miatto, Filippo M; Mirhosseini, Mohammad; Magaña-Loaiza, Omar S; Liapis, Andreas C; Oi, Daniel K L; Boyd, Robert W; Jeffers, John

2015-10-16

In 1924 David Hilbert conceived a paradoxical tale involving a hotel with an infinite number of rooms to illustrate some aspects of the mathematical notion of "infinity." In continuous-variable quantum mechanics we routinely make use of infinite state spaces: here we show that such a theoretical apparatus can accommodate an analog of Hilbert's hotel paradox. We devise a protocol that, mimicking what happens to the guests of the hotel, maps the amplitudes of an infinite eigenbasis to twice their original quantum number in a coherent and deterministic manner, producing infinitely many unoccupied levels in the process. We demonstrate the feasibility of the protocol by experimentally realizing it on the orbital angular momentum of a paraxial field. This new non-Gaussian operation may be exploited, for example, for enhancing the sensitivity of NOON states, for increasing the capacity of a channel, or for multiplexing multiple channels into a single one.

Vers une approche globale de l'évolution des HominidésTowards an all-round approach to Hominid evolution

NASA Astrophysics Data System (ADS)

Chaline, Jean

1998-03-01

Two models of diversification of the common ancestor of gorillas, chimpanzees and men can be proposed on the basis of the distribution of chromosomal rearrangements in extant species and reconsideration of the role played by climate. The small genetic divergence between chimpanzees and humans is greatly amplified at the morphological level, thus constituting the 'human paradox'. This paradox is resolved by the economical and flexible evolutionary mechanism of mutations in regulator genes and the heterochronies they control, which are the true internal clocks of evolution. Changes in cranial morphology are quantified and used to analyse and explain the steps in the transition from great ape to human morphology. By comparison at the various stages of development, it is suggested that from great apes to modern man numerous heterochronies have occured during ontogeny (hypermorphosis, hypomorphosis and post-displacements).

Salience driven value integration explains decision biases and preference reversal

PubMed Central

Tsetsos, Konstantinos; Chater, Nick; Usher, Marius

2012-01-01

Human choice behavior exhibits many paradoxical and challenging patterns. Traditional explanations focus on how values are represented, but little is known about how values are integrated. Here we outline a psychophysical task for value integration that can be used as a window on high-level, multiattribute decisions. Participants choose between alternative rapidly presented streams of numerical values. By controlling the temporal distribution of the values, we demonstrate that this process underlies many puzzling choice paradoxes, such as temporal, risk, and framing biases, as well as preference reversals. These phenomena can be explained by a simple mechanism based on the integration of values, weighted by their salience. The salience of a sampled value depends on its temporal order and momentary rank in the decision context, whereas the direction of the weighting is determined by the task framing. We show that many known choice anomalies may arise from the microstructure of the value integration process. PMID:22635271

The Gender-Equality Paradox in Science, Technology, Engineering, and Mathematics Education.

PubMed

Stoet, Gijsbert; Geary, David C

2018-04-01

The underrepresentation of girls and women in science, technology, engineering, and mathematics (STEM) fields is a continual concern for social scientists and policymakers. Using an international database on adolescent achievement in science, mathematics, and reading ( N = 472,242), we showed that girls performed similarly to or better than boys in science in two of every three countries, and in nearly all countries, more girls appeared capable of college-level STEM study than had enrolled. Paradoxically, the sex differences in the magnitude of relative academic strengths and pursuit of STEM degrees rose with increases in national gender equality. The gap between boys' science achievement and girls' reading achievement relative to their mean academic performance was near universal. These sex differences in academic strengths and attitudes toward science correlated with the STEM graduation gap. A mediation analysis suggested that life-quality pressures in less gender-equal countries promote girls' and women's engagement with STEM subjects.

The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids.

PubMed

Perez-Vizcaino, Francisco; Duarte, Juan; Santos-Buelga, Celestino

2012-07-01

Flavonoids have been proposed to exert beneficial effects in the prevention of a large number of diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. Paradoxically, despite the most representative flavonoid--quercetin--exerting biologically demonstrable systemic effects, it is not found in plasma after oral administration and its circulating metabolites show weak activity in vitro. The current available evidence indicates that quercetin is extensively metabolized into methylated and glucurono- and sulfo-conjugated metabolites, which are the plasma circulating forms; and glucurono-, but not sulfo-conjugates, can be hydrolyzed at the vascular level, yielding the parent aglycone which accumulates in tissues. Thus conjugation is a reversible process and, at least regarding the vasodilator and antihypertensive effects, the conjugation-deconjugation cycle appears to be an absolute requirement. Glucuronidated derivatives transport quercetin and its methylated form, and deliver to the tissues the free aglycone, which is the final effector. Copyright © 2012 Society of Chemical Industry.

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

PubMed

Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

2018-05-04

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Proteasome inhibitors alter levels of intracellular peptides in HEK293T and SH-SY5Y cells.

PubMed

Dasgupta, Sayani; Castro, Leandro M; Dulman, Russell; Yang, Ciyu; Schmidt, Marion; Ferro, Emer S; Fricker, Lloyd D

2014-01-01

The proteasome cleaves intracellular proteins into peptides. Earlier studies found that treatment of human embryonic kidney 293T (HEK293T) cells with epoxomicin (an irreversible proteasome inhibitor) generally caused a decrease in levels of intracellular peptides. However, bortezomib (an antitumor drug and proteasome inhibitor) caused an unexpected increase in the levels of most intracellular peptides in HEK293T and SH-SY5Y cells. To address this apparent paradox, quantitative peptidomics was used to study the effect of a variety of other proteasome inhibitors on peptide levels in HEK293T and SH-SY5Y cells. Inhibitors tested included carfilzomib, MG132, MG262, MLN2238, AM114, and clasto-Lactacystin β-lactone. Only MG262 caused a substantial elevation in peptide levels that was comparable to the effect of bortezomib, although carfilzomib and MLN2238 elevated the levels of some peptides. To explore off-target effects, the proteosome inhibitors were tested with various cellular peptidases. Bortezomib did not inhibit tripeptidyl peptidase 2 and only weakly inhibited cellular aminopeptidase activity, as did some of the other proteasome inhibitors. However, potent inhibitors of tripeptidyl peptidase 2 (butabindide) and cellular aminopeptidases (bestatin) did not substantially alter the peptidome, indicating that the increase in peptide levels due to proteasome inhibitors is not a result of peptidase inhibition. Although we cannot exclude other possibilities, we presume that the paradoxical increase in peptide levels upon treatment with bortezomib and other inhibitors is the result of allosteric effects of these compounds on the proteasome. Because intracellular peptides are likely to be functional, it is possible that some of the physiologic effects of bortezomib and carfilzomib arise from the perturbation of peptide levels inside the cell.

Proteasome Inhibitors Alter Levels of Intracellular Peptides in HEK293T and SH-SY5Y Cells

PubMed Central

Dasgupta, Sayani; Castro, Leandro M.; Dulman, Russell; Yang, Ciyu; Schmidt, Marion; Ferro, Emer S.; Fricker, Lloyd D.

2014-01-01

The proteasome cleaves intracellular proteins into peptides. Earlier studies found that treatment of human embryonic kidney 293T (HEK293T) cells with epoxomicin (an irreversible proteasome inhibitor) generally caused a decrease in levels of intracellular peptides. However, bortezomib (an antitumor drug and proteasome inhibitor) caused an unexpected increase in the levels of most intracellular peptides in HEK293T and SH-SY5Y cells. To address this apparent paradox, quantitative peptidomics was used to study the effect of a variety of other proteasome inhibitors on peptide levels in HEK293T and SH-SY5Y cells. Inhibitors tested included carfilzomib, MG132, MG262, MLN2238, AM114, and clasto-Lactacystin β-lactone. Only MG262 caused a substantial elevation in peptide levels that was comparable to the effect of bortezomib, although carfilzomib and MLN2238 elevated the levels of some peptides. To explore off-target effects, the proteosome inhibitors were tested with various cellular peptidases. Bortezomib did not inhibit tripeptidyl peptidase 2 and only weakly inhibited cellular aminopeptidase activity, as did some of the other proteasome inhibitors. However, potent inhibitors of tripeptidyl peptidase 2 (butabindide) and cellular aminopeptidases (bestatin) did not substantially alter the peptidome, indicating that the increase in peptide levels due to proteasome inhibitors is not a result of peptidase inhibition. Although we cannot exclude other possibilities, we presume that the paradoxical increase in peptide levels upon treatment with bortezomib and other inhibitors is the result of allosteric effects of these compounds on the proteasome. Because intracellular peptides are likely to be functional, it is possible that some of the physiologic effects of bortezomib and carfilzomib arise from the perturbation of peptide levels inside the cell. PMID:25079948

Quantum paradoxes, entanglement and their explanation on the basis of quantization of fields

NASA Astrophysics Data System (ADS)

Melkikh, A. V.

2017-01-01

Quantum entanglement is discussed as a consequence of the quantization of fields. The inclusion of quantum fields self-consistently explains some quantum paradoxes (EPR and Hardy’s paradox). The definition of entanglement was introduced, which depends on the maximum energy of the interaction of particles. The destruction of entanglement is caused by the creation and annihilation of particles. On this basis, an algorithm for quantum particle evolution was formulated.

A simple test of expected utility theory using professional traders.

PubMed

List, John A; Haigh, Michael S

2005-01-18

We compare behavior across students and professional traders from the Chicago Board of Trade in a classic Allais paradox experiment. Our experiment tests whether independence, a necessary condition in expected utility theory, is systematically violated. We find that both students and professionals exhibit some behavior consistent with the Allais paradox, but the data pattern does suggest that the trader population falls prey to the Allais paradox less frequently than the student population.

The core paradox.

NASA Technical Reports Server (NTRS)

Kennedy, G. C.; Higgins, G. H.

1973-01-01

Rebuttal of suggestions from various critics attempting to provide an escape from the seeming paradox originated by Higgins and Kennedy's (1971) proposed possibility that the liquid in the outer core was thermally stably stratified and that this stratification might prove a powerful inhibitor to circulation of the outer core fluid of the kind postulated for the generation of the earth's magnetic field. These suggestions are examined and shown to provide no reasonable escape from the core paradox.

Fault-tolerant Greenberger-Horne-Zeilinger paradox based on non-Abelian anyons.

PubMed

Deng, Dong-Ling; Wu, Chunfeng; Chen, Jing-Ling; Oh, C H

2010-08-06

We propose a scheme to test the Greenberger-Horne-Zeilinger paradox based on braidings of non-Abelian anyons, which are exotic quasiparticle excitations of topological states of matter. Because topological ordered states are robust against local perturbations, this scheme is in some sense "fault-tolerant" and might close the detection inefficiency loophole problem in previous experimental tests of the Greenberger-Horne-Zeilinger paradox. In turn, the construction of the Greenberger-Horne-Zeilinger paradox reveals the nonlocal property of non-Abelian anyons. Our results indicate that the non-Abelian fractional statistics is a pure quantum effect and cannot be described by local realistic theories. Finally, we present a possible experimental implementation of the scheme based on the anyonic interferometry technologies.

Black Hole Paradoxes

NASA Astrophysics Data System (ADS)

Joshi, Pankaj S.; Narayan, Ramesh

2016-10-01

We propose here that the well-known black hole paradoxes such as the information loss and teleological nature of the event horizon are restricted to a particular idealized case, which is the homogeneous dust collapse model. In this case, the event horizon, which defines the boundary of the black hole, forms initially, and the singularity in the interior of the black hole at a later time. We show that, in contrast, gravitational collapse from physically more realistic initial conditions typically leads to the scenario in which the event horizon and space-time singularity form simultaneously. We point out that this apparently simple modification can mitigate the causality and teleological paradoxes, and also lends support to two recently suggested solutions to the information paradox, namely, the ‘firewall’ and ‘classical chaos’ proposals.

IL-15 regulates Bcl-2 family members Bim and Mcl-1 through JAK/STAT and PI3K/AKT pathways in T cells.

PubMed

Shenoy, Aparna R; Kirschnek, Susanne; Häcker, Georg

2014-08-01

Maintenance of T cells is determined by their survival capacity, which is regulated by Bcl-2 proteins. Cytokines signalling through the common gamma chains such as IL-2, IL-7 and IL-15 are important for T-cell survival but how these cytokines determine the expression of Bcl-2-family proteins is not clear. We report signalling events of cytokines that regulate expression of two key Bcl-2 proteins, pro-apoptotic Bim and anti-apoptotic Mcl-1, in resting C57BL/6 mouse T cells. IL-2, IL-7 and IL-15 inhibited apoptosis but paradoxically induced the expression of Bim, countered by concomitant induction of Mcl-1. Bim induction by IL-15 was found at the mRNA and protein levels and depended on both JAK/STAT and PI3K signals. A new STAT5-binding site was identified in the Bim promoter, which was occupied by STAT5 upon IL-15 stimulation. Although it also depended on JAK/STAT- and PI3K signalling, Mcl-1 regulation was independent of Mcl-1 mRNA levels and of regulation of protein stability, suggesting translational regulation. Concurrent CD3 signals inhibited some of the IL-7 effect but not the IL-15 effect on Bcl-2 proteins. The data suggest that cytokines induce Bim and prime T cells for apoptosis, but also inhibit apoptosis by stabilising Mcl-1. Later downregulation of short-lived Mcl-1 may induce efficient, Bim-dependent apoptosis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Leptin levels in protracted critical illness: effects of growth hormone-secretagogues and thyrotropin-releasing hormone.

PubMed

Van den Berghe, G; Wouters, P; Carlsson, L; Baxter, R C; Bouillon, R; Bowers, C Y

1998-09-01

Prolonged critical illness is characterized by feeding-resistant wasting of protein, whereas reesterification, instead of oxidation of fatty acids, allows fat stores to accrue and associate with a low-activity status of the somatotropic and thyrotropic axis, which seems to be partly of hypothalamic origin. To further unravel this paradoxical metabolic condition, and in search of potential therapeutic strategies, we measured serum concentrations of leptin; studied the relationship with body mass index, insulin, cortisol, thyroid hormones, and somatomedins; and documented the effects of hypothalamic releasing factors, in particular, GH-secretagogues and TRH. Twenty adults, critically ill for several weeks and supported with normocaloric, continuously administered parenteral and/or enteral feeding, were studied for 45 h. They had been randomized to receive one of three combinations of peptide infusions, in random order: TRH (one day) and placebo (other day); TRH + GH-releasing peptide (GHRP)-2 and GHRP-2; TRH + GHRH + GHRP-2 and GHRH + GHRP-2. Peptide infusions were started after a 1-microgram/kg bolus at 0900 h and infused (1 microgram/kg.h) until 0600 h the next morning. Serum concentrations of leptin, insulin, cortisol, T4, T3, insulin-like growth factor (IGF)-I, IGF-binding protein-3 and the acid-labile subunit (ALS) were measured at 0900 h, 2100 h, and 0600 h on each of the 2 study days. Baseline leptin levels (mean +/- SEM: 12.4 +/- 2.1 micrograms/L) were independent of body mass index (25 +/- 1 kg/m2), insulin (18.6 +/- 2.9 microIU/mL), cortisol (504 +/- 43 mmol/L), and thyroid hormones (T4: 63 +/- 5 nmol/L, T3: 0.72 +/- 0.08 nmol/L) but correlated positively with circulating levels of IGF-I [86 +/- 6 micrograms/L, determination coefficient (R2) = 0.25] and ALS (7.2 +/- 0.6 mg/L, R2 = 0.32). Infusion of placebo or TRH had no effect on leptin. In contrast, GH-secretagogues elevated leptin levels within 12 h. Infusion of GHRP-2 alone induced a maximal leptin increase of +87% after 24 h, whereas GHRH + GHRP-2 elevated leptin by up to +157% after 24 h. The increase in leptin within 12 h was related (R2 = 0.58) to the substantial rise in insulin. After 45 h, and having reached a plateau, leptin was related to the increased IGF-I (R2 = 0.37). In conclusion, circulating leptin levels during protracted critical illness were linked to the activity state of the GH/IGF-I axis. Stimulating the GH/IGF-I axis with GH-secretagogues increased leptin levels within 12 h. Because leptin may stimulate oxidation of fatty acids, and because GH, IGF-I, and insulin have a protein-sparing effect, GH-secretagogue administration may be expected to result in increased utilization of fat as preferential substrate and to restore protein content in vital tissues and, consequently, has potential as a strategy to reverse the paradoxical metabolic condition of protracted critical illness.

Effects of sub-clinical psychosis and cognitive insight on psychological well-being: a structural equation model.

PubMed

Weintraub, Marc J; Weisman de Mamani, Amy

2015-03-30

Psychological well-being has been widely researched along the psychosis spectrum, and increased psychotic symptoms are generally associated with worse well-being. Additionally, the construct of insight has been extensively studied in schizophrenia. While having greater insight has many benefits for those with schizophrenia, a paradox exists in which greater insight is also associated with poorer psychological well-being. However, it is unclear whether the link between insight and poor well-being occurs only once serious psychopathology has been established, or whether this is a more universal process seen even at lower levels on the psychosis spectrum. We used a structural modeling approach in an ethnically diverse, non-clinical sample of 420 undergraduates to evaluate the association between sub-clinical psychosis, cognitive insight and psychological well-being. As hypothesized, results indicated that sub-clinical psychotic symptoms were negatively associated with psychological well-being. The insight paradox was also substantiated, as greater cognitive insight was associated with worse psychological well-being. However, cognitive insight did not moderate the association between symptoms and well-being. The link between sub-clinical psychotic symptoms and psychological well-being as well as the insight paradox appears to emerge even before reaching threshold for a psychotic disorder. Research and clinical implications are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Is There a Sex-Related Difference in the Obesity Paradox in Systolic Heart Failure? Sex-Related Difference in the Obesity Paradox.

PubMed

Hong, Soonchang; Lee, Ji Hyun; Kim, Kyung Min; Lee, Jun Won; Youn, Young Jin; Ahn, Min Soo; Ahn, Sung Gyun; Lee, Seung Hwan; Yoon, Junghan; Choe, Kyung Hoon; Yoo, Byung Su

2018-01-01

Obesity is often associated with better clinical outcomes in heart failure (HF). This so-called obesity paradox remains controversial. The aim of present study was to investigate the prognostic value of obesity in patients hospitalized for systolic HF. We performed a pooled analysis of data from two multicenter, observational HF studies. Patients hospitalized for systolic HF were eligible for the present study. We divided the subjects into two groups, a normal body mass index (BMI) group and a high BMI group. Study endpoints included all-cause mortality and any re-hospitalization within 1 year. We enrolled 3145 patients (male, 1824; female, 1321). The high BMI group was significantly associated with lower 1-year mortality rate [odds ratio (OR), 0.543; 95% confidence interval (CI), 0.355-0.832] after adjusting for age, hypertension, diabetes, ischemic HF, previous myocardial infarction, serum creatinine level, anemia, and ejection fraction in men. After adjustment for clinical characteristics, high BMI was not significantly associated with 1-year mortality (OR, 0.739; 95% CI, 0.450-1.216) or 1-year re-hospitalization (OR, 0.958; 95% CI, 0.696-1.319) in women. In pooled analysis of data from two Korean HF registries, the high BMI group was independently associated with lower 1-year mortality rate from systolic HF, especially in men. © Copyright: Yonsei University College of Medicine 2018

The Policy Maker's Anguish: Regulating Personal Data Behavior Between Paradoxes and Dilemmas

NASA Astrophysics Data System (ADS)

Compañó, Ramón; Lusoli, Wainer

Regulators in Europe and elsewhere are paying great attention to identity, privacy and trust in online and converging environments. Appropriate regulation of identity in a ubiquitous information environment is seen as one of the major drivers of the future Internet economy. Regulation of personal identity data has come to the fore including mapping conducted on digital personhood by the OECD; work on human rights and profiling by the Council of Europe andmajor studies by the European Commission with regard to self-regulation in the privacy market, electronic identity technical interoperability and enhanced safety for young people. These domains overlap onto an increasingly complex model of regulation of individuals' identity management, online and offline. This chapter argues that policy makers struggle to deal with issues concerning electronic identity, due to the apparently irrational and unpredictable behavior of users when engaging in online interactions involving identity management. Building on empirical survey evidence from four EU countries, we examine the first aspect in detail - citizens' management of identity in a digital environment. We build on data from a large scale (n = 5,265) online survey of attitudes to electronic identity among young Europeans (France, Germany, Spain, UK) conducted in August 2008. The survey asked questions about perceptions and acceptance of risks, general motivations, attitudes and behaviors concerning electronic identity. Four behavioral paradoxes are identified in the analysis: a privacy paradox (to date well known), but also a control paradox, a responsibility paradox and an awareness paradox. The chapter then examines the paradoxes in relation of three main policy dilemmas framing the debate on digital identity. The paper concludes by arguing for an expanded identity debate spanning policy circles and the engineering community.

A simple test of expected utility theory using professional traders

PubMed Central

List, John A.; Haigh, Michael S.

2005-01-01

We compare behavior across students and professional traders from the Chicago Board of Trade in a classic Allais paradox experiment. Our experiment tests whether independence, a necessary condition in expected utility theory, is systematically violated. We find that both students and professionals exhibit some behavior consistent with the Allais paradox, but the data pattern does suggest that the trader population falls prey to the Allais paradox less frequently than the student population. PMID:15634739

Comments on Surrogates measures and consistent surrogates (by Tyler VanderWeele)

DTIC Science & Technology

2013-03-01

as a criterion for “good” surrogate, why can’t we create a new, formal definition of “ surrogacy ” that (1) will automatically avoid the paradox and (2...requirement of avoiding the paradox could not, in itself, constitute a satisfactory definition of surrogacy . As with other paradoxes of causal...situation in practice. A treatment that has such a negative direct effect on outcome would rarely be a candidate for surrogacy analysis. In practice

Permanent tensions in organization.

PubMed

Jansson, Noora

2015-01-01

The purpose of this paper is to investigate the relationship between permanent tensions and organizational change. This study used paradox theory and a case study. The case organization is a public university hospital in Finland involving several stakeholders. The analysis suggests that the relationship between permanent tensions and organizational change is a paradox that is part of organizational reality. As an organization learns to live with its permanent tensions, the renewal paradox settles into equilibrium. When tensions are provoked, the paradox is disturbed until it finds a new balance. This flexible nature of the paradox is the force that keeps the different stakeholders simultaneously empowered to maintain their unique missions and cohesive in order to benefit from the larger synergy. This research suggests that identification and evaluation of each permanent tension within an organization is important when executing organizational change. The fact that certain tensions are permanent and cannot be solved may have an influence on how planned change initiatives are executed. The results show that permanent tensions may be harnessed for the benefit of an organizational change. This research demonstrates originality by offering an alternative view of tensions, a view which emphasizes not only their permanent and plural nature but their importance for enabling the organization to change at its own, non-disruptive pace. The research also proposes a new concept, the "renewal paradox", to enhance understanding of the relationship between permanent tensions and organizational change.

Obesity paradox and the heart: which indicator of obesity best describes this complex relationship?

PubMed

De Schutter, Alban; Lavie, Carl J; Patel, Dharmendrakumar A; Milani, Richard V

2013-09-01

Despite the detrimental effects of obesity on coronary heart disease (CHD) and heart failure, obesity is found to be paradoxically associated with improved survival in secondary care of CHD and heart failure. This 'obesity paradox' is an area of active research, and it might be the result of an inaccurate working definition of obesity, which is traditionally defined in terms of BMI. We reviewed the recent literature on the paradox and examined different anthropomorphic measurements and their association with prognosis in cardiovascular diseases. In CHD, obesity is associated with improved prognosis when defined by high BMI and body fat, independent of fat-free mass (FFM). High waist circumference seems to be associated with worse prognosis in some studies, but is associated with protection and an obesity paradox in those with poor cardiorespiratory fitness (CRF). In patients with heart failure, BMI, body fat and waist circumference, and possibly FFM, have been associated with improved survival. Despite these findings, intentional weight loss remains protective. In both CHD and heart failure, CRF seems to significantly impact the relationship between adiposity and subsequent prognosis, and an obesity paradox is only present with low CRF. Body composition, including waist circumference, body fat and FFM have a role in clinical practice. Emphasis should be placed on improving CRF, regardless of weight status. Intentional weight loss, particularly while maintaining FFM, should be encouraged in obese individuals.

Where Was Everybody? Olaf Stapledon and the Fermi Paradox

NASA Astrophysics Data System (ADS)

Baxter, S.

In 1948 Olaf Stapledon gave an address to the BIS in which he summarised his vision of mankind's cosmic future: `One can imagine some sort of cosmical community of worlds ...' One might ask, however, since the universe is vastly older than mankind, why races on other worlds have not already built such a community. This is a `Fermi Paradox' question. The Paradox is based on the observation that there has been time for extraterrestrial intelligence to arise and colonise the Galaxy many times over, yet we see no sign of such endeavours. In this paper Stapledon's novels are retrospectively analysed from the point of view of the Fermi Paradox. In Last and First Men (1930) humanity is forever isolated because life and mind are rare in the Galaxy, and interstellar distances are too large ever to be traversed. These are classic candidate Fermi `solutions'. The `solution' implicit in Star Maker (1937) might be criticised in that it posits that humanity lives at a special epoch, with the cosmically transforming development of interstellar travel occurring a `mere' ten billion years after mankind, in a universe supposedly ~200bn years old. Stapledon died in 1950, the year the Paradox was formulated, and was probably unaware of the Paradox. However to apply retrospectively Fermi thinking to Stapledon's cosmologies is to gain a new insight into the author's philosophy.

Length Paradox in Relativity

ERIC Educational Resources Information Center

Martins, Roberto de A.

1978-01-01

Describes a thought experiment using a general analysis approach with Lorentz transformations to show that the apparent self-contradictions of special relativity concerning the length-paradox are really non-existant. (GA)

Paradox lost. The latah problem revisited.

PubMed

Kenny, M G

1983-03-01

This paper examines the validity of Dr. R. C. Simons' resolution (Simons, R. C. The resolution of the latah paradox. J. Nerv. Ment. Dis., 168: 195-206, 1980) of the so-called latah paradox. Latah, a Malay condition precipitated by sudden fright and involving compulsive obscenity and mimesis, was found to be closely related to local cultural values; yet a paradox seems to arise from the fact that analogous conditions are reported from unrelated cultures. Simons accounts for this by proposing that latah and its kindred states are based on the universal human startle reflex and that latah is merely a culture-specific exploitation of a neurophysiological potential shared by humans and other animals. It is here argued that the evidence does not support such a view and that latah-like conditions are best considered in terms of their local meaning within their societies of origin; ethnographic material from Siberia is examined as a case in point. It is concluded that the "latah paradox" is illusory and that biomedical approaches to the question have seriously misread the nature of the phenomenon and potentially distort clinical practice in relation to it.

Salivary α-amylase, serum albumin, and myoglobin protect against DNA-damaging activities of ingested dietary agents in vitro

PubMed Central

Hossain, M. Zulfiquer; Patel, Kalpesh; Kern, Scott E.

2014-01-01

Potent DNA-damaging activities were seen in vitro from dietary chemicals found in coffee, tea, and liquid smoke. A survey of tea varieties confirmed genotoxic activity to be widespread. Constituent pyrogallol-like polyphenols (PLPs) such as epigallocatechin-3-gallate (EGCG), pyrogallol, and gallic acid were proposed as a major source of DNA-damaging activities, inducing DNA double-strand breaks in the p53R assay, a well characterized assay sensitive to DNA strand breaks, and comet assay. Paradoxically, their consumption does not lead to the kind of widespread cellular toxicity and acute disease that might be expected from genotoxic exposure. Existing physiological mechanisms could limit DNA damage from dietary injurants. Serum albumin and salivary α-amylase are known to bind EGCG. Salivary α-amylase, serum albumin, and myoglobin, but not salivary proline-rich proteins, reduced damage from tea, coffee, and PLPs, but did not inhibit damage from the chemotherapeutics etoposide and camptothecin. This represents a novel function for saliva in addition to its known functions including protection against tannins. Cell populations administered repeated pyrogallol exposures had abatement of measured DNA damage by two weeks, indicating an innate cellular adaptation. We suggest that layers of physiological protections may exist toward natural dietary products to which animals have had high-level exposure over evolution. PMID:24842839

Upregulation of LYAR induces neuroblastoma cell proliferation and survival.

PubMed

Sun, Yuting; Atmadibrata, Bernard; Yu, Denise; Wong, Matthew; Liu, Bing; Ho, Nicholas; Ling, Dora; Tee, Andrew E; Wang, Jenny; Mungrue, Imran N; Liu, Pei Y; Liu, Tao

2017-09-01

The N-Myc oncoprotein induces neuroblastoma by regulating gene transcription and consequently causing cell proliferation. Paradoxically, N-Myc is well known to induce apoptosis by upregulating pro-apoptosis genes, and it is not clear how N-Myc overexpressing neuroblastoma cells escape N-Myc-mediated apoptosis. The nuclear zinc finger protein LYAR has recently been shown to modulate gene expression by forming a protein complex with the protein arginine methyltransferase PRMT5. Here we showed that N-Myc upregulated LYAR gene expression by binding to its gene promoter. Genome-wide differential gene expression studies revealed that knocking down LYAR considerably upregulated the expression of oxidative stress genes including CHAC1, which depletes intracellular glutathione and induces oxidative stress. Although knocking down LYAR expression with siRNAs induced oxidative stress, neuroblastoma cell growth inhibition and apoptosis, co-treatment with the glutathione supplement N-acetyl-l-cysteine or co-transfection with CHAC1 siRNAs blocked the effect of LYAR siRNAs. Importantly, high levels of LYAR gene expression in human neuroblastoma tissues predicted poor event-free and overall survival in neuroblastoma patients, independent of the best current markers for poor prognosis. Taken together, our data suggest that LYAR induces proliferation and promotes survival of neuroblastoma cells by repressing the expression of oxidative stress genes such as CHAC1 and suppressing oxidative stress, and identify LYAR as a novel co-factor in N-Myc oncogenesis.

Salivary α-amylase, serum albumin, and myoglobin protect against DNA-damaging activities of ingested dietary agents in vitro.

PubMed

Hossain, M Zulfiquer; Patel, Kalpesh; Kern, Scott E

2014-08-01

Potent DNA-damaging activities were seen in vitro from dietary chemicals found in coffee, tea, and liquid smoke. A survey of tea varieties confirmed genotoxic activity to be widespread. Constituent pyrogallol-like polyphenols (PLPs) such as epigallocatechin-3-gallate (EGCG), pyrogallol, and gallic acid were proposed as a major source of DNA-damaging activities, inducing DNA double-strand breaks in the p53R assay, a well characterized assay sensitive to DNA strand breaks, and comet assay. Paradoxically, their consumption does not lead to the kind of widespread cellular toxicity and acute disease that might be expected from genotoxic exposure. Existing physiological mechanisms could limit DNA damage from dietary injurants. Serum albumin and salivary α-amylase are known to bind EGCG. Salivary α-amylase, serum albumin, and myoglobin, but not salivary proline-rich proteins, reduced damage from tea, coffee, and PLPs, but did not inhibit damage from the chemotherapeutics etoposide and camptothecin. This represents a novel function for saliva in addition to its known functions including protection against tannins. Cell populations administered repeated pyrogallol exposures had abatement of measured DNA damage by two weeks, indicating an innate cellular adaptation. We suggest that layers of physiological protections may exist toward natural dietary products to which animals have had high-level exposure over evolution. Copyright © 2014 Elsevier Ltd. All rights reserved.

Paradoxes and Dilemmas in Managing E-Learning in Higher Education. Research & Occasional Paper Series. CSHE.7.03

ERIC Educational Resources Information Center

Guri-Rosenblit, Sarah

2003-01-01

The new information and communication technologies (ICT) affect currently most spheres of life, including all educational levels. Their effects are most likely to grow in the future. However, many predictions in the last few years as to the sweeping impact of the ICT on restructuring the teaching/learning practices at universities and their high…

Toward a Unified Knowledge-based Society for Sustainability -- Developing a Synthesis on the Methodological Level

Treesearch

Alec A. Schaerer

2006-01-01

The debates on development manifest an increasing concern for sustainability, but as yet little awareness of the hierarchy in the ideas through which humans contribute to the problem. This gap is widened by a widespread but nevertheless unnecessary acceptance of unreasonable elements such as paradoxes, or the general fragmentation in knowledge, or allegedly general...

The Bicyclist's Paradox

ERIC Educational Resources Information Center

Knight, Randy

2008-01-01

It's a situation every avid cyclist knows only too well. If you cycle up a hill and then back down with no net change in elevation, it seems as if your slower uphill speed and faster downhill speed should offset each other. But they don't. Your average speed is less than it would have been had you cycled the same distance on a level road.…

A Triarchic Model for Teaching "Introduction to Special Education": Case Studies, Content Acquisition Podcasts, and Effective Feedback

ERIC Educational Resources Information Center

Kennedy, Michael J.; Newton, Jennier R.; Haines, Shana J.; Walther-Thomas, Christine S.; Kellems, Ryan O.

2012-01-01

Those who teach introductory level courses in special education to preservice teacher candidates often face a paradox in terms of whether to use limited instructional time to either focus on characteristics of students with disabilities or emphasize evidence-based practices (EBPs). The issue of limited instructional time is also an issue in other…

The Latino Male Educational Trajectory: A Precollege Econometric Model and 21st Century Implications

ERIC Educational Resources Information Center

Ortiz, Ramon, Jr.

2017-01-01

The twin challenges of aging demographics in the United States and the need for higher levels of education to compete in the new technology-based economy is creating a socioeconomic paradox (Friedman, 2005). As the Baby Boomer generation retires, those replacing them are increasingly a non-White population. This demographic shift is inevitable and…

The Changing Value of Vigorous Activity and the Paradox of Utilising Exercise as Punishment in Physical Education

ERIC Educational Resources Information Center

Aasland, Erik; Walseth, Kristin; Engelsrud, Gunn

2017-01-01

Background: Previous research on physical education (PE) teaching practice indicates that an exercise physiology discourse has assumed a dominant position within the field. Research shows that PE teachers are likely to emphasise physical fitness training in their teaching, and PE teachers seem to appreciate pupils who show high levels of physical…

The Paradox of Tradition and Modernity in Female Education in the Islamic Republic of Iran.

ERIC Educational Resources Information Center

Mehran, Golnar

2003-01-01

Since the 1979 revolution, Iranian women have been expected to fulfill the traditional role of women under Islamic law while contributing to the modern needs of their country. Iranian women have access to a wide range of (gender-segregated) educational opportunities and are drawing on their relatively high levels of educational attainment to…

Geological sulfur isotopes indicate elevated OCS in the Archean atmosphere, solving faint young sun paradox.

PubMed

Ueno, Yuichiro; Johnson, Matthew S; Danielache, Sebastian O; Eskebjerg, Carsten; Pandey, Antra; Yoshida, Naohiro

2009-09-01

Distributions of sulfur isotopes in geological samples would provide a record of atmospheric composition if the mechanism producing the isotope effects could be described quantitatively. We determined the UV absorption spectra of 32SO2, 33SO2, and 34SO2 and use them to interpret the geological record. The calculated isotopic fractionation factors for SO2 photolysis give mass independent distributions that are highly sensitive to the atmospheric concentrations of O2, O3, CO2, H2O, CS2, NH3, N2O, H2S, OCS, and SO2 itself. Various UV-shielding scenarios are considered and we conclude that the negative Delta33S observed in the Archean sulfate deposits can only be explained by OCS shielding. Of relevant Archean gases, OCS has the unique ability to prevent SO2 photolysis by sunlight at lambda >202 nm. Scenarios run using a photochemical box model show that ppm levels of OCS will accumulate in a CO-rich, reducing Archean atmosphere. The radiative forcing, due to this level of OCS, is able to resolve the faint young sun paradox. Further, the decline of atmospheric OCS may have caused the late Archean glaciation.

The gender-job satisfaction paradox and the dual-earner society: Are women (still) making work-family trade-offs?

PubMed

Grönlund, Anne; Öun, Ida

2018-01-01

Despite their disadvantaged labour market position, women consistently report higher levels of job satisfaction than men. Researchers have attributed women's higher job satisfaction to their lower expectations, arguing that gender differences will fade away as women's labour market prospects improve. Others, however, argue that women are more contented than men because their jobs satisfy a need for family adaptions. In this article, we put the hypotheses of transitions and trade-offs to a strong test, by comparing men and women with comparable human capital investments living in a country where women's employment is strongly supported by policies, practices and social norms. The relationship between gender and job satisfaction is analysed with stepwise OLS regressions. The analysis is based on a survey to newly graduated highly educated men and women in five occupations in Sweden (n ≈ 2 450). First, we show that, after controlling for a range of job characteristics, women report a higher level of job satisfaction than men. Second, although the paradox appears to be surprisingly persistent, it cannot be attributed to work-family trade-offs. Future research should consider job satisfaction more broadly in the light of gender role socialization and persistent gender inequalities.

A mathematical modelling approach to assessing the reliability of biomarkers of glutathione metabolism.

PubMed

Geenen, Suzanne; du Preez, Franco B; Reed, Michael; Nijhout, H Frederik; Kenna, J Gerry; Wilson, Ian D; Westerhoff, Hans V; Snoep, Jacky L

2012-07-16

One of the main pathways for the detoxification of reactive metabolites in the liver involves glutathione conjugation. Metabolic profiling studies have shown paradoxical responses in glutathione-related biochemical pathways. One of these is the increase in 5-oxoproline and ophthalmic acid concentrations with increased dosage of paracetamol. Experimental studies have thus far failed to resolve these paradoxes and the robustness of how these proposed biomarkers correlate with liver glutathione levels has been questioned. To better understand how these biomarkers behave in the glutathione system a kinetic model of this pathway was made. By using metabolic control analysis and by simulating biomarker levels under a variety of conditions, we found that 5-oxoproline and ophthalmic acid concentrations may not only depend on the glutathione but also on the methionine status of the cell. We show that neither of the two potential biomarkers are reliable on their own since they need additional information about the methionine status of the system to relate them uniquely to intracellular glutathione concentration. However, when both biomarkers are measured simultaneously a direct inference of the glutathione concentration can be made, irrespective of the methionine concentration in the system. Copyright © 2011 Elsevier B.V. All rights reserved.

Geological sulfur isotopes indicate elevated OCS in the Archean atmosphere, solving faint young sun paradox

PubMed Central

Ueno, Yuichiro; Johnson, Matthew S.; Danielache, Sebastian O.; Eskebjerg, Carsten; Pandey, Antra; Yoshida, Naohiro

2009-01-01

Distributions of sulfur isotopes in geological samples would provide a record of atmospheric composition if the mechanism producing the isotope effects could be described quantitatively. We determined the UV absorption spectra of 32SO2, 33SO2, and 34SO2 and use them to interpret the geological record. The calculated isotopic fractionation factors for SO2 photolysis give mass independent distributions that are highly sensitive to the atmospheric concentrations of O2, O3, CO2, H2O, CS2, NH3, N2O, H2S, OCS, and SO2 itself. Various UV-shielding scenarios are considered and we conclude that the negative Δ33S observed in the Archean sulfate deposits can only be explained by OCS shielding. Of relevant Archean gases, OCS has the unique ability to prevent SO2 photolysis by sunlight at λ >202 nm. Scenarios run using a photochemical box model show that ppm levels of OCS will accumulate in a CO-rich, reducing Archean atmosphere. The radiative forcing, due to this level of OCS, is able to resolve the faint young sun paradox. Further, the decline of atmospheric OCS may have caused the late Archean glaciation. PMID:19706450

Glutamate microinjection in the medial septum of rats decreases paradoxical sleep and increases slow wave sleep.

PubMed

Mukherjee, Didhiti; Kaushik, Mahesh K; Jaryal, Ashok Kumar; Kumar, Velayudhan Mohan; Mallick, Hruda Nanda

2012-05-09

The role of the medial septum in suppressing paradoxical sleep and promoting slow wave sleep was suggested on the basis of neurotoxic lesion studies. However, these conclusions need to be substantiated with further experiments, including chemical stimulation studies. In this report, the medial septum was stimulated in adult male rats by microinjection of L-glutamate. Sleep-wakefulness was electrophysiologically recorded, through chronically implanted electrodes, for 2 h before the injection and 4 h after the injection. There was a decrease in paradoxical sleep during the first hour and an increase in slow wave sleep during the second hour after the injection. The present findings not only supported the lesion studies but also showed that the major role of the medial septum is to suppress paradoxical sleep.

Management of Paradoxical Response in Pediatric Tubercular Meningitis with Methylprednisolone

PubMed Central

Nema, Nitin; Verma, Abha; Singh, Kuldeep; Mehar, Virendra

2014-01-01

Paradoxical response to anti-tubercular drugs remains a diagnostic dilemma. In India where tuberculosis is quite prevalent, paradoxical response to anti-tubercular treatment (ATT) is either misdiagnosed or under-diagnosed. We report two cases of optochiasmatic arachnoiditis due to paradoxical response in children suffering from tuberculous meningitis. Visual acuity was recorded as no light perception in all eyes of both patients while they were taking 4-drug ATT (isoniazid, rifampicin, pyrazinamide and ethambutol). However their systemic conditions did not worsen. They were treated with intravenous methylprednisolone for five days followed by systemic corticosteroids on a tapering dose for four weeks along with ATT. This case report highlights the importance of early recognition of this sight-threatening complication and timely, effective treatment to prevent permanent blindness. PMID:24791114

The forgotten cause of stridor in the emergency department.

PubMed

Ng, Tian-Tee

2017-01-01

Paradoxical Vocal Fold Movement Disorder is where the larynx exhibits paradoxical vocal cords closure during respiration, creating partial airway obstruction. Causes of vocal fold movement disorder are multifactorial, and patients describe tightness of throat, difficulty getting air in, have stridor, and do not respond to inhalers. We propose using transnasal laryngoscopy examination, which will show narrowing of vocal cords on inspiration, and The Pittsburgh Vocal Cord Dysfunction Index with a cutoff score of ≥4 to distinguish vocal fold movement disorder from asthma and other causes of stridor. Management of paradoxical vocal fold movement disorder involves a combination of pharmacological, psychological, psychiatric, and speech training. Paradoxical vocal fold movement disorder is a very treatable cause of stridor, so long as it is identified and other organic causes are excluded.

Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yogesha, S.D.; Sharff, Andrew J.; Giovannini, Marco

The merlin-1 tumor suppressor is encoded by the Neurofibromatosis-2 (Nf2) gene and loss-of-function Nf2 mutations lead to nervous system tumors in man and to several tumor types in mice. Merlin is an ERM (ezrin, radixin, moesin) family cytoskeletal protein that interacts with other ERM proteins and with components of cell-cell adherens junctions (AJs). Merlin stabilizes the links of AJs to the actin cytoskeleton. Thus, its loss destabilizes AJs, promoting cell migration and invasion, which in Nf2{sup +/-} mice leads to highly metastatic tumors. Paradoxically, the 'closed' conformation of merlin-1, where its N-terminal four-point-one, ezrin, radixin, moesin (FERM) domain binds tomore » its C-terminal tail domain, directs its tumor suppressor functions. Here we report the crystal structure of the human merlin-1 head domain when crystallized in the presence of its tail domain. Remarkably, unlike other ERM head-tail interactions, this structure suggests that binding of the tail provokes dimerization and dynamic movement and unfurling of the F2 motif of the FERM domain. We conclude the 'closed' tumor suppressor conformer of merlin-1 is in fact an 'open' dimer whose functions are disabled by Nf2 mutations that disrupt this architecture.« less

A Case Study of Small Group Decision-Making as Influenced by the Abilene Paradox: The ’Challenger’ Mishap

DTIC Science & Technology

1988-05-01

RESEARCH REPORT O A CASE STUDY OF SMALL GROUP DECISION-MAKING AS INFLUENCED BY THE ABILENE PARADOX: N THE " CHALLENGER " MISHAP COMMANDER JAMES Y...1.09_240 AIR WAR COLLEGE AIR UNIVERSITY A CASE STIJI)Y OF SMALL GROUP DECISION-MAKING AS INFLUENCED BY THE ABILENE PARADOX: THE " CHALLENGER " MISHAP by...representing the public and private sectors of leadership in our national space exploration program evaluated the risk associated with known discrepancies

Fuzzy spaces topology change as a possible solution to the black hole information loss paradox

NASA Astrophysics Data System (ADS)

Silva, C. A. S.

2009-06-01

The black hole information loss paradox is one of the most intricate problems in modern theoretical physics. A proposal to solve this is one related with topology change. However it has found some obstacles related to unitarity and cluster decomposition (locality). In this Letter we argue that modelling the black hole's event horizon as a noncommutative manifold - the fuzzy sphere - we can solve the problems with topology change, getting a possible solution to the black hole information loss paradox.

Galileo's Paradox

NASA Astrophysics Data System (ADS)

Greenslade, Thomas B.

2008-05-01

The paradox is a wonderful teaching tool. The sleepy student in the back row is surprised and wakes up, and the student with the instantly memorized answer is forced into the analytical mode. The diagram in Fig. 1 has the following paradox: A body sliding freely down a chord from the edge of the circle reaches the lowest point on the circle at the same time as a body released simultaneously from the top. This result was first mentioned in a 1602 letter from Galileo Galilei to Guidobaldo dal Monte.

Nucleolin Mediates MicroRNA-directed CSF-1 mRNA Deadenylation but Increases Translation of CSF-1 mRNA*

PubMed Central

Woo, Ho-Hyung; Baker, Terri; Laszlo, Csaba; Chambers, Setsuko K.

2013-01-01

CSF-1 mRNA 3′UTR contains multiple unique motifs, including a common microRNA (miRNA) target in close proximity to a noncanonical G-quadruplex and AU-rich elements (AREs). Using a luciferase reporter system fused to CSF-1 mRNA 3′UTR, disruption of the miRNA target region, G-quadruplex, and AREs together dramatically increased reporter RNA levels, suggesting important roles for these cis-acting regulatory elements in the down-regulation of CSF-1 mRNA. We find that nucleolin, which binds both G-quadruplex and AREs, enhances deadenylation of CSF-1 mRNA, promoting CSF-1 mRNA decay, while having the capacity to increase translation of CSF-1 mRNA. Through interaction with the CSF-1 3′UTR miRNA common target, we find that miR-130a and miR-301a inhibit CSF-1 expression by enhancing mRNA decay. Silencing of nucleolin prevents the miRNA-directed mRNA decay, indicating a requirement for nucleolin in miRNA activity on CSF-1 mRNA. Downstream effects followed by miR-130a and miR-301a inhibition of directed cellular motility of ovarian cancer cells were found to be dependent on nucleolin. The paradoxical effects of nucleolin on miRNA-directed CSF-1 mRNA deadenylation and on translational activation were explored further. The nucleolin protein contains four acidic stretches, four RNA recognition motifs (RRMs), and nine RGG repeats. All three domains in nucleolin regulate CSF-1 mRNA and protein levels. RRMs increase CSF-1 mRNA, whereas the acidic and RGG domains decrease CSF-1 protein levels. This suggests that nucleolin has the capacity to differentially regulate both CSF-1 RNA and protein levels. Our finding that nucleolin interacts with Ago2 indirectly via RNA and with poly(A)-binding protein C (PABPC) directly suggests a nucleolin-Ago2-PABPC complex formation on mRNA. This complex is in keeping with our suggestion that nucleolin may work with PABPC as a double-edged sword on both mRNA deadenylation and translational activation. Our findings underscore the complexity of nucleolin's actions on CSF-1 mRNA and describe the dependence of miR-130a- and miR-301a-directed CSF-1 mRNA decay and inhibition of ovarian cancer cell motility on nucleolin. PMID:23471483

Thermal Expansion "Paradox."

ERIC Educational Resources Information Center

Fakhruddin, Hasan

1993-01-01

Describes a paradox in the equation for thermal expansion. If the calculations for heating a rod and subsequently cooling a rod are determined, the new length of the cool rod is shorter than expected. (PR)

The nature-disorder paradox: A perceptual study on how nature is disorderly yet aesthetically preferred.

PubMed

Kotabe, Hiroki P; Kardan, Omid; Berman, Marc G

2017-08-01

Natural environments have powerful aesthetic appeal linked to their capacity for psychological restoration. In contrast, disorderly environments are aesthetically aversive, and have various detrimental psychological effects. But in our research, we have repeatedly found that natural environments are perceptually disorderly. What could explain this paradox? We present 3 competing hypotheses: the aesthetic preference for naturalness is more powerful than the aesthetic aversion to disorder (the nature-trumps-disorder hypothesis ); disorder is trivial to aesthetic preference in natural contexts (the harmless-disorder hypothesis ); and disorder is aesthetically preferred in natural contexts (the beneficial-disorder hypothesis ). Utilizing novel methods of perceptual study and diverse stimuli, we rule in the nature-trumps-disorder hypothesis and rule out the harmless-disorder and beneficial-disorder hypotheses. In examining perceptual mechanisms, we find evidence that high-level scene semantics are both necessary and sufficient for the nature-trumps-disorder effect. Necessity is evidenced by the effect disappearing in experiments utilizing only low-level visual stimuli (i.e., where scene semantics have been removed) and experiments utilizing a rapid-scene-presentation procedure that obscures scene semantics. Sufficiency is evidenced by the effect reappearing in experiments utilizing noun stimuli which remove low-level visual features. Furthermore, we present evidence that the interaction of scene semantics with low-level visual features amplifies the nature-trumps-disorder effect-the effect is weaker both when statistically adjusting for quantified low-level visual features and when using noun stimuli which remove low-level visual features. These results have implications for psychological theories bearing on the joint influence of low- and high-level perceptual inputs on affect and cognition, as well as for aesthetic design. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Small molecule activation of PKM2 in cancer cells induces serine auxotrophy.

PubMed

Kung, Charles; Hixon, Jeff; Choe, Sung; Marks, Kevin; Gross, Stefan; Murphy, Erin; DeLaBarre, Byron; Cianchetta, Giovanni; Sethumadhavan, Shalini; Wang, Xiling; Yan, Shunqi; Gao, Yi; Fang, Cheng; Wei, Wentao; Jiang, Fan; Wang, Shaohui; Qian, Kevin; Saunders, Jeff; Driggers, Ed; Woo, Hin Koon; Kunii, Kaiko; Murray, Stuart; Yang, Hua; Yen, Katharine; Liu, Wei; Cantley, Lewis C; Vander Heiden, Matthew G; Su, Shinsan M; Jin, Shengfang; Salituro, Francesco G; Dang, Lenny

2012-09-21

Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM2 isoform, effectively constraining lower glycolysis. Here, we report the discovery of PKM2 activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM2 activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the nonessential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM2 activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM2 expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

Adenosine A2B receptor: from cell biology to human diseases

NASA Astrophysics Data System (ADS)

Sun, Ying; Huang, Pingbo

2016-08-01

Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide array of biological processes. Recently, significant advances have been made in our understanding of A2B adenosine receptor (A2BAR). In this review, we first summarize some of the general characteristics of A2BAR, and then we describe the multiple binding partners of the receptor, such as newly identified α-actinin-1 and p105, and discuss how these associated proteins could modulate A2BAR’s functions, including certain seemingly paradoxical functions of the receptor. Growing evidence indicates a critical role of A2BAR in cancer, renal disease, and diabetes, in addition to its importance in the regulation of vascular diseases and lung disease. Here, we also discuss the role of A2BAR in cancer, renal disease, and diabetes and the potential of the receptor as a target for treating these three diseases.

Small Molecule Activation of PKM2 in Cancer Cells Induces Serine Auxotrophy

PubMed Central

Kung, Charles; Hixon, Jeff; Choe, Sung; Marks, Kevin; Gross, Stefan; Murphy, Erin; DeLaBarre, Byron; Cianchetta, Giovanni; Sethumadhavan, Shalini; Wang, Xiling; Yan, Shunqi; Gao, Yi; Fang, Cheng; Wei, Wentao; Jiang, Fan; Wang, Shaohui; Qian, Kevin; Saunders, Jeff; Driggers, Ed; Woo, Hin Koon; Kunii, Kaiko; Murray, Stuart; Yang, Hua; Yen, Katharine; Liu, Wei; Cantley, Lewis C.; Vander Heiden, Matthew G.; Su, Shinsan M.; Jin, Shengfang; Salituro, Francesco G.; Dang, Lenny

2013-01-01

SUMMARY Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM2 isoform, effectively constraining lower glycolysis. Here, we report the discovery of PKM2 activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM2 activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the nonessential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM2 activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM2 expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress. PMID:22999886

The Anderson localization problem, the Fermi-Pasta-Ulam paradox and the generalized diffusion approach

NASA Astrophysics Data System (ADS)

Kuzovkov, V. N.

2011-12-01

The goal of this paper is twofold. First, based on the interpretation of a quantum tight-binding model in terms of a classical Hamiltonian map, we consider the Anderson localization (AL) problem as the Fermi-Pasta-Ulam (FPU) effect in a modified dynamical system containing both stable and unstable (inverted) modes. Delocalized states in the AL are analogous to the stable quasi-periodic motion in FPU, whereas localized states are analogous to thermalization, respectively. The second aim is to use the classical Hamilton map for a simplified derivation of exact equations for the localization operator H(z). The latter was presented earlier (Kuzovkov et al 2002 J. Phys.: Condens. Matter 14 13777) treating the AL as a generalized diffusion in a dynamical system. We demonstrate that counter-intuitive results of our studies of the AL are similar to the FPU counter-intuitivity.

Colonic epithelial cell activation and the paradoxical effects of butyrate.

PubMed

Gibson, P R; Rosella, O; Wilson, A J; Mariadason, J M; Rickard, K; Byron, K; Barkla, D H

1999-04-01

Butyrate may have paradoxical effects on epithelial cells of similar origin. This study aimed to examine the hypothesis that one mechanism that dictates a cell's response to butyrate is its state of activation. First, the responses to 24 h exposure to butyrate (1-2 mM) of normal and neoplastic human colonic epithelial cells activated by their isolation and primary culture, and of colon cancer cell lines, LIM1215 and Caco-2, were examined. In primary cultures of normal and cancer cells, butyrate had no effect on alkaline phosphatase activities but significantly suppressed urokinase receptor expression by a mean +/- SEM of 30 +/- 12% and 36 +/- 9%, respectively. Interleukin-8 secretion was suppressed by 44 +/- 7% in normal cells (P < 0.05) but was unchanged in cancer cells. In contrast, the cell lines significantly increased alkaline phosphatase activities by >50%, urokinase receptor expression >2-fold and interleukin-8 secretion >3-fold in response to butyrate. Secondly, the effect of butyrate on Caco-2 cells was examined with or without prior exposure to a specific activating stimulus [tumour necrosis factor alpha (TNF alpha)]. Interleukin-8 secretion increased by 145 +/- 23% and 132 +/- 17% on 24 h exposure to 2 mM butyrate or 0.1 microM TNF alpha alone, respectively. However, in cells pre-treated with TNF alpha, butyrate significantly inhibited secretion by 34 +/- 7% below unstimulated levels. The response to butyrate of urokinase receptor, whose expression was not stimulated by TNF alpha, was unchanged. These effects were mimicked by trichostatin A, an inhibitor of histone deacetylase, suggesting that butyrate's paradoxical effects may have been operating by the same mechanism. In conclusion, some of the paradoxical effects of butyrate do not appear to represent inherent differences between normal and transformed cells. Rather, the response may be determined by the state of activation of the cells.

The impact of inflammation on the obesity paradox in coronary heart disease.

PubMed

De Schutter, A; Kachur, S; Lavie, C J; Boddepalli, R S; Patel, D A; Milani, R V

2016-11-01

Despite the well-known adverse effects of obesity on almost all aspects of coronary heart disease, many studies of coronary heart disease cohorts have demonstrated an inverse relationship between obesity, as defined by body mass index (BMI), and subsequent prognosis: the 'obesity paradox'. The etiology of this and the potential role of inflammation in this process remain unknown. We studied 519 patients with coronary heart disease before and after cardiac rehabilitation, dividing them into groups based on C-reactive protein ((CRP)⩾3 mg l -1 and CRP<3 mg l -1 after cardiac rehabilitation). BMI was calculated and body fat was measured using the skin-fold method. Lean mass index (LMI) was calculated as (1-%body fat) × BMI. The population was divided according to age- and gender-adjusted categories based on LMI and body fat and analyzed by total mortality over >3-year follow-up by National Death Index in both CRP groups. During >3-year follow-up, all-cause mortality was higher in the high inflammation and in the low BMI group. In proportional hazard analysis, even after adjusting for ejection fraction and peak O 2 consumption, higher BMI was associated with lower mortality in the entire population (hazard ratio (HR) 0.38; confidence interval 0.15-0.97) and a trend to lower mortality in both subgroups (HR 0.45 in low CRP, P=0.24 vs HR 0.32, P=0.06 in high CRP). High body fat, however, was associated with significantly lower mortality in the high CRP group (HR 0.22; P=0.03) but not in the low CRP group (HR 0.73; P=0.64). Conversely, high LMI was associated with markedly lower mortality in the low CRP group (HR 0.04; P=0.04). The obesity paradox has multiple underlying etiologies. Body composition has a different role in different populations with an obesity paradox by BMI. Especially in the subpopulation with persistently high CRP levels, body fat seems protective.

Modification of caffeine-induced injury in Ca2+-free perfused rat hearts. Relationship to the calcium paradox.

PubMed Central

Vander Heide, R. S.; Altschuld, R. A.; Lamka, K. G.; Ganote, C. E.

1986-01-01

The pathogenesis of the calcium paradox has not been established. In calcium-free perfused hearts, caffeine, which releases calcium from the sarcoplasmic reticulum, causes severe myocardial injury, with creatine kinase (CK) release and contraction band necrosis similar in many respects to the calcium paradox. It has been postulated that contracture, initiated by a small rise in intracellular calcium, may cause sarcolemmal injury in both the calcium paradox and caffeine-induced myocardial injury. The present study was initiated to determine whether interventions which modulate caffeine-induced contracture will also correspondingly alter cellular injury. The effects of caffeine dose, procaine, extended calcium-free perfusion, elevated potassium, temperature, and increasing intracellular sodium on caffeine-induced contracture were examined in Langendorff-perfused adult rat hearts. Caffeine-induced contracture at 22 C increased over a dose range of 5-40 mM caffeine. Procaine, which inhibits caffeine-induced calcium release at doses between 5 and 20 mM, progressively reduced contracture caused by addition of 20 mM caffeine at 22 C. Hearts perfused with calcium-free solution containing 16 mM K+ showed a reduction in caffeine-induced contracture. Extended calcium-free perfusion (20 minutes) at temperatures from 18 to 37 C resulted in a progressive reduction of caffeine-induced contracture. Each of these interventions was also found to inhibit caffeine-induced injury at 37 C. Low temperature was found to have complex effects. Hypothermia enhanced caffeine contractures but also protected hearts from cell separations and CK release. Increasing intracellular sodium was found to enhance caffeine-induced contracture at 37 C. There was a direct correlation between measured intracellular sodium levels and the magnitude and duration of caffeine-induced contracture. These results demonstrate a direct correlation between the magnitude of contracture and myocardial injury in calcium-free hearts. It is proposed that contracture is the primary mediator of sarcolemmal membrane injury in hearts with intercalated disks weakened by prior calcium-free perfusion. Images Figure 11 PMID:3706496

Paradoxical effects of antioxidants on cancer.

PubMed

Mendelsohn, Andrew R; Larrick, James W

2014-06-01

Antioxidants have had a checkered history concerning their reported ability to prevent or treat cancer. Early studies that showed ascorbate had benefit in cancer were followed by more definitive studies that demonstrated no benefit. Recent work suggests that biological context may be key to predicting whether antioxidants impede or even promote tumorigenesis. In a recent report, the antioxidants N-acetylcysteine and vitamin E accelerated tumorigenesis of lung cancer in mice. antioxidants decrease reactive oxygen species (ROS) levels, which paradoxically increase the proliferation rate of lung cancer cells, resulting in greater tumor burdens and reduced survival. Increased proliferation rates result from decreased expression of the genomic watchdog protein p53. In mice lacking p53, neither anti-oxidant affects tumor growth. But antioxidants can be used to kill cancer, at least in rodents. High concentrations of the "antioxidant" ascorbate, achievable only by injection in vivo, result in the production of ascorbate radicals and hydrogen peroxide in the extracellular fluid that kills cancer cells, but not normal cells. In preliminary human trials, ascorbate reduced the toxicity of chemotherapy, but showed no statistical benefit on disease progression. Vitamin C is beneficial when it acts as an oxidant. These studies are consistent with others that suggest that even tumor suppressor genes, such as Nrf2, which stimulate innate cellular stress protection pathways that reduce ROS, can promote cancer progression. Nrf2 is required for the cancer preventive effects of compounds such as sulforaphane, but Nrf2 can help maintain an aggressive tumor phenotype by stimulating proliferation and offering protection from chemotherapy. Context determines whether a specific gene is a tumor enhancer or a suppressor. Such paradoxical behavior creates difficult problems for the development of conventional therapeutics to fight cancer. Personal genomic analysis may provide the means to identify context to avoid these paradoxes and obtain a successful outcome. However, cancer prevention may be more difficult than previously thought.

Theoretical study of interaction of winter flounder antifreeze protein with ice

PubMed Central

Jorov, Alexander; Zhorov, Boris S.; Yang, Daniel S.C.

2004-01-01

Antifreeze proteins (AFPs) are synthesized by various organisms to enable their cells to survive subzero environment. These proteins bind to small ice crystals and inhibit their growth, which if left uncontrolled would be fatal to cells. The crystal structures of a number of AFPs have been determined; however, crystallographic analysis of AFP–ice complex is nearly impossible. Molecular modeling studies of AFPs’ interaction with ice surface is therefore invaluable. Early models of AFP–ice interaction suggested H-bond as the primary driving force behind such interaction. Recent experimental evidence, however, suggested that hydrophobic interactions could be the main contributor to AFP–ice association. All computational studies published to date were carried out to verify the H-bond model, and no works attempting to verify the hydrophobic interaction model have been published. In this work, we Monte Carlo–minimized complexes of several AFPs with ice taking into account nonbonded interactions, H-bonds, and the hydration potential for proteins. Parameters of the hydration potential for ice were developed with the assumption that the free energy of the water–ice association should be close to zero at equilibrium melting temperature. Our calculations demonstrate that desolvation of hydrophobic groups in the AFPs upon their binding to the grooves at the ice surface is indeed the major stabilizing contributor to the free energy of AFP–ice binding. This study is consistent with available structural and mutation data on AFPs. In particular, it explains the paradoxical finding that substitution of Thr residues with Val does not affect the potency of winter flounder AFP whereas substitution with Ser abolished its antifreeze activity. PMID:15152087

A Paradox: α-Klotho Levels and Smoking Intensity.

PubMed

Verde, Zoraida; González-Moro, Jose M Rodríguez; Chicharro, Luis M; Reinoso-Barbero, Luis; Bandrés, Fernando; Gómez-Gallego, Félix; Santiago, Catalina

2017-02-01

Reports regarding smoking differences in α-klotho expression have provided conflicting results. In the current study we focused on the influence of smoking intensity to serum levels of the aging molecule α-klotho in healthy smokers. 40 middle aged healthy smokers without airway obstruction or restriction were selected for the analysis. Serum levels of soluble α-klotho were significantly higher in heavy smokers (P < 0.001). These results are in agreement with the possibility that α-klotho acts as anti-inflammatory molecule and strengthen the hypothesis that an increase of serum levels of α-klotho might be a compensatory response to smoking stress in healthy population.

A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis

PubMed Central

2011-01-01

Background The skeletal elements of vertebrate embryonic limbs are prefigured by rod- and spot-like condensations of precartilage mesenchymal cells. The formation of these condensations depends on cell-matrix and cell-cell interactions, but how they are initiated and patterned is as yet unresolved. Results Here we provide evidence that galectins, β-galactoside-binding lectins with β-sandwich folding, play fundamental roles in these processes. We show that among the five chicken galectin (CG) genes, two, CG-1A, and CG-8, are markedly elevated in expression at prospective sites of condensation in vitro and in vivo, with their protein products appearing earlier in development than any previously described marker. The two molecules enhance one another's gene expression but have opposite effects on condensation formation and cartilage development in vivo and in vitro: CG-1A, a non-covalent homodimer, promotes this process, while the tandem-repeat-type CG-8 antagonizes it. Correspondingly, knockdown of CG-1A inhibits the formation of skeletal elements while knockdown of CG-8 enhances it. The apparent paradox of mutual activation at the gene expression level coupled with antagonistic roles in skeletogenesis is resolved by analysis of the direct effect of the proteins on precartilage cells. Specifically, CG-1A causes their aggregation, whereas CG-8, which has no adhesive function of its own, blocks this effect. The developmental appearance and regulation of the unknown cell surface moieties ("ligands") to which CG-1A and CG-8 bind were indicative of specific cognate- and cross-regulatory interactions. Conclusion Our findings indicate that CG-1A and CG-8 constitute a multiscale network that is a major mediator, earlier-acting than any previously described, of the formation and patterning of precartilage mesenchymal condensations in the developing limb. This network functions autonomously of limb bud signaling centers or other limb bud positional cues. PMID:21284876

The effect of information technology investment on firm-level performance in the health care industry.

PubMed

Thouin, Mark F; Hoffman, James J; Ford, Eric W

2008-01-01

The return on investment for information technology (IT) has been the subject of much debate throughout the history of management information systems research. Often referred to as the productivity paradox, increased IT investments have not been consistently associated with increased productivity. Understanding individual IT factors that directly contribute to business value should provide insight into the productivity paradox. The effects of 3 different firm-level IT characteristics on financial performance in the health care industry are studied. Specifically, the effects of IT budget, IT outsourcing, and the relative number of IT personnel on firm-level financial performance are analyzed. Regression analysis of archival survey data for 914 Integrated Healthcare Delivery Systems is performed. IT budgetary expenditures and the number of IT services outsourced are associated with increases in the profitability of Integrated Healthcare Delivery Systems, whereas increases in IT personnel are not significantly associated with increased profitability. Each one tenth of a percentage increase in IT expenditures is associated with approximately $100,000 in increased profit, and each additional IT service outsourced is associated with approximately $950,000 in increased profit for an average-sized Integrated Healthcare Delivery System. To increase profitability, IT administrators should increase IT budgetary expenditures along with IT outsourcing levels. IT administrators in the health care industry can use such findings during budgeting cycles to justify increased investments in IT personnel as being budget neutral while increasing organizational capacity.

Space Curvature and the "Heavy Banana 'Paradox.'"

ERIC Educational Resources Information Center

Gruber, Ronald P.; And Others

1991-01-01

Two ways to visually enhance the concept of space curvature are described. Viewing space curvature as a meterstick contraction and the heavy banana "paradox" are discussed. The meterstick contraction is mathematically explained. (KR)

The Paradoxical Role of the Research Administrator.

ERIC Educational Resources Information Center

White, Virginia P.

1991-01-01

This reprinted 1970 article examines the role of the university research administrator and finds that the role involves paradoxes between controller and entrepreneur, master and slave, censor and publicist, and traditionalist and innovator. (DB)

Colloquium: The Einstein-Podolsky-Rosen paradox: From concepts to applications

NASA Astrophysics Data System (ADS)

Reid, M. D.; Drummond, P. D.; Bowen, W. P.; Cavalcanti, E. G.; Lam, P. K.; Bachor, H. A.; Andersen, U. L.; Leuchs, G.

2009-10-01

This Colloquium examines the field of the Einstein, Podolsky, and Rosen (EPR) gedanken experiment, from the original paper of Einstein, Podolsky, and Rosen, through to modern theoretical proposals of how to realize both the continuous-variable and discrete versions of the EPR paradox. The relationship with entanglement and Bell’s theorem are analyzed, and the progress to date towards experimental confirmation of the EPR paradox is summarized, with a detailed treatment of the continuous-variable paradox in laser-based experiments. Practical techniques covered include continuous-wave parametric amplifier and optical fiber quantum soliton experiments. Current proposals for extending EPR experiments to massive-particle systems are discussed, including spin squeezing, atomic position entanglement, and quadrature entanglement in ultracold atoms. Finally, applications of this technology to quantum key distribution, quantum teleportation, and entanglement swapping are examined.

A new consequence of Simpson's paradox: stable cooperation in one-shot prisoner's dilemma from populations of individualistic learners.

PubMed

Chater, Nick; Vlaev, Ivo; Grinberg, Maurice

2008-08-01

Theories of choice in economics typically assume that interacting agents act individualistically and maximize their own utility. Specifically, game theory proposes that rational players should defect in one-shot prisoners' dilemmas (PD). Defection also appears to be the inevitable outcome for agents who learn by reinforcement of past choices, because whatever the other player does, defection leads to greater reinforcement on each trial. In a computer simulation and 4 experiments, the authors show that, apparently paradoxically, when players' choices are correlated by an exogenous factor (here, the cooperativeness of the specific PD chosen), people obtain greater average reinforcement for cooperating, which can sustain cooperation. This effect arises from a well-known statistical paradox, Simpson's paradox. The authors speculate that this effect may be relevant to aspects of real-world human cooperative behavior.

The adaptation of non-western and Muslim immigrant adolescents in the Netherlands: An immigrant paradox?

PubMed

Van Geel, Mitch; Vedder, Paul

2010-10-01

This article addresses the possible existence of an immigrant paradox in a sample of immigrant adolescents attending vocational schools in the Netherlands. An immigrant paradox is the finding that first generation immigrants show a more positive pattern of adaptation than nationals despite poorer economic conditions. Second generation immigrants regress to the nationals in terms of adaptation. A sample of 152 first generation immigrant adolescents, 285 second generation immigrant adolescents and 406 national adolescents completed self-reports about socio-economic status, psychological problems, behavioral problems and self-esteem. The results supported the existence of an immigrant paradox in this sample. This indicates that further assimilation among immigrant adolescents does not necessarily lead to increased well being. © 2010 The Authors. Scandinavian Journal of Psychology © 2010 The Scandinavian Psychological Associations.

Molecular pathological epidemiology gives clues to paradoxical findings.

PubMed

Nishihara, Reiko; VanderWeele, Tyler J; Shibuya, Kenji; Mittleman, Murray A; Wang, Molin; Field, Alison E; Giovannucci, Edward; Lochhead, Paul; Ogino, Shuji

2015-10-01

A number of epidemiologic studies have described what appear to be paradoxical associations, where an incongruous relationship is observed between a certain well-established risk factor for disease incidence and favorable clinical outcome among patients with that disease. For example, the "obesity paradox" represents the association between obesity and better survival among patients with a certain disease such as coronary heart disease. Paradoxical observations cause vexing clinical and public health problems as they raise questions on causal relationships and hinder the development of effective interventions. Compelling evidence indicates that pathogenic processes encompass molecular alterations within cells and the microenvironment, influenced by various exogenous and endogenous exposures, and that interpersonal heterogeneity in molecular pathology and pathophysiology exists among patients with any given disease. In this article, we introduce methods of the emerging integrative interdisciplinary field of molecular pathological epidemiology (MPE), which is founded on the unique disease principle and disease continuum theory. We analyze and decipher apparent paradoxical findings, utilizing the MPE approach and available literature data on tumor somatic genetic and epigenetic characteristics. Through our analyses in colorectal cancer, renal cell carcinoma, and glioblastoma (malignant brain tumor), we can readily explain paradoxical associations between disease risk factors and better prognosis among disease patients. The MPE paradigm and approach can be applied to not only neoplasms but also various non-neoplastic diseases where there exists indisputable ubiquitous heterogeneity of pathogenesis and molecular pathology. The MPE paradigm including consideration of disease heterogeneity plays an essential role in advancements of precision medicine and public health.

Brain extracellular glucose assessed by voltammetry throughout the rat sleep-wake cycle.

PubMed

Netchiporouk, L; Shram, N; Salvert, D; Cespuglio, R

2001-04-01

In the present study, cortical extracellular levels of glucose were monitored for the first time throughout the sleep-wake states of the freely moving rat. For this purpose, polygraphic recordings (electroencephalogram of the fronto-occipital cortices and electromyogram of the neck muscles) were achieved in combination with differential normal pulse voltammetry (DNPV) using a specific glucose sensor. Data obtained reveal that the basal extracellular glucose concentration in the conscious rat is 0.59 +/- 0.3 m M while under chloral hydrate anaesthesia (0.4 g/kg, i.p.) it increases up to 180% of its basal concentration. Regarding the sleep-wake cycle, the existence of spontaneous significant variations in the mean glucose level during slow-wave sleep (SWS = +13%) and paradoxical sleep (PS = -11%) compared with the waking state (100%) is also reported. It is to be noticed that during long periods of active waking, glucose level tends towards a decrease that becomes significant after 15 min (active waking = -32%). On the contrary, during long episodes of slow-wave sleep, it tends towards an increase which becomes significant after 12 min (SWS = +28%). It is suggested that voltammetric techniques using enzymatic biosensors are useful tools allowing direct glucose measurements in the freely moving animal. On the whole, paradoxical sleep is pointed out as a state highly dependent on the availability of energy and slow-wave sleep as a period of energy saving.

The mean, the median, and the St. Petersburg paradox

PubMed Central

Hayden, Benjamin Y.; Platt, Michael L.

2013-01-01

The St. Petersburg Paradox is a famous economic and philosophical puzzle that has generated numerous conflicting explanations. To shed empirical light on this phenomenon, we examined subjects’ bids for one St. Petersburg gamble with a real monetary payment. We found that bids were typically lower than twice the smallest payoff, and thus much lower than is generally supposed. We also examined bids offered for several hypothetical variants of the St. Petersburg Paradox. We found that bids were weakly affected by truncating the gamble, were strongly affected by repeats of the gamble, and depended linearly on the initial “seed” value of the gamble. One explanation, which we call the median heuristic, strongly predicts these data. Subjects following this strategy evaluate a gamble as if they were taking the median rather than the mean of the payoff distribution. Finally, we argue that the distribution of outcomes embodied in the St. Petersburg paradox is so divergent from the Gaussian form that the statistical mean is a poor estimator of expected value, so that the expected value of the St. Petersburg gamble is undefined. These results suggest that this classic paradox has a straightforward explanation rooted in the use of a statistical heuristic. PMID:24179560

An alternative resolution to the Mansuripur paradox

NASA Astrophysics Data System (ADS)

Redfern, Francis

2016-04-01

In 2013 an article published online by the journal Science declared that the paradox proposed by Masud Mansuripur was resolved. This paradox concerns a point charge-Amperian magnetic dipole system as seen in a frame of reference where they are at rest and one in which they are moving. In the latter frame an electric dipole appears on the magnetic dipole. A torque is then exerted upon the electric dipole by the point charge, a torque that is not observed in the at-rest frame. Mansuripur points out this violates the relativity principle and suggests the Lorentz force responsible for the torque be replaced by the Einstein-Laub force. The resolution of the paradox reported by Science, based on numerous papers in the physics literature, preserves the Lorentz force but depends on the concept of hidden momentum. Here I propose a different resolution based on the overlooked fact that the charge-magnetic dipole system contains linear and angular electromagnetic field momentum. The time rate of change of the field angular-momentum in the frame through which the system is moving cancels that due to the charge-electric dipole interaction. From this point of view hidden momentum is not needed in the resolution of the paradox.

Pricing of drugs with heterogeneous health insurance coverage.

PubMed

Ferrara, Ida; Missios, Paul

2012-03-01

In this paper, we examine the role of insurance coverage in explaining the generic competition paradox in a two-stage game involving a single producer of brand-name drugs and n quantity-competing producers of generic drugs. Independently of brand loyalty, which some studies rely upon to explain the paradox, we show that heterogeneity in insurance coverage may result in higher prices of brand-name drugs following generic entry. With market segmentation based on insurance coverage present in both the pre- and post-entry stages, the paradox can arise when the two types of drugs are highly substitutable and the market is quite profitable but does not have to arise when the two types of drugs are highly differentiated. However, with market segmentation occurring only after generic entry, the paradox can arise when the two types of drugs are weakly substitutable, provided, however, that the industry is not very profitable. In both cases, that is, when market segmentation is present in the pre-entry stage and when it is not, the paradox becomes more likely to arise as the market expands and/or insurance companies decrease deductibles applied on the purchase of generic drugs. Copyright © 2012 Elsevier B.V. All rights reserved.

An understanding of nurse educators' leadership behaviors in implementing mandatory continuing nursing education in China.

PubMed

Xiao, Lily Dongxia

2008-09-01

Mandatory continuing nursing education is viewed as one way to develop registered nurses' continuing competencies. However, as has been argued internationally, it can also create a paradox in terms of learning to meet study requirements. Such paradox has been discussing in China since the implementation of mandatory continuing nursing education in 1996. Nurse educators, who develop continuing nursing education programs, appear to respond to the paradox differently associated with their leadership styles. This article reports a qualitative study aiming to gain an understanding of nurse educators' leadership behaviors in implementing mandatory continuing nursing education in China. Gadamer's philosophical hermeneutics underpins in-depth interviews with five nurse educators and data interpretation. Two categories of nurse educators, described as proactive educator and reactive educator, were identified and compared with two types of leadership styles described as transformational leader and transactional leader in the literature of educational leadership and continuing professional development. Proactive educators shared core attributors of transformational leaders and were able to relieve the paradox in mandatory continuing nursing education. Reactive educators however showed some attributors of transactional leaders and might escalate the paradox. Findings suggest further research in relation to the preparation of nurse educators.

The mean, the median, and the St. Petersburg paradox.

PubMed

Hayden, Benjamin Y; Platt, Michael L

2009-06-01

The St. Petersburg Paradox is a famous economic and philosophical puzzle that has generated numerous conflicting explanations. To shed empirical light on this phenomenon, we examined subjects' bids for one St. Petersburg gamble with a real monetary payment. We found that bids were typically lower than twice the smallest payoff, and thus much lower than is generally supposed. We also examined bids offered for several hypothetical variants of the St. Petersburg Paradox. We found that bids were weakly affected by truncating the gamble, were strongly affected by repeats of the gamble, and depended linearly on the initial "seed" value of the gamble. One explanation, which we call the median heuristic , strongly predicts these data. Subjects following this strategy evaluate a gamble as if they were taking the median rather than the mean of the payoff distribution. Finally, we argue that the distribution of outcomes embodied in the St. Petersburg paradox is so divergent from the Gaussian form that the statistical mean is a poor estimator of expected value, so that the expected value of the St. Petersburg gamble is undefined. These results suggest that this classic paradox has a straightforward explanation rooted in the use of a statistical heuristic.

The paradox of mental health: over-treatment and under-recognition.

PubMed

2013-01-01

The PLOS Medicine editors discuss the paradox of mental health, where over-diagnosis and treatment of some mental health issues exists alongside profound under-recognition of mental health conditions in the developing world.

Moderate red wine consumption and cardiovascular disease risk: beyond the "French paradox".

PubMed

Lippi, Giuseppe; Franchini, Massimo; Favaloro, Emmanuel J; Targher, Giovanni

2010-02-01

The term FRENCH PARADOX was coined in 1992 to describe the relatively low incidence of cardiovascular disease in the French population, despite a relatively high dietary intake of saturated fats, and potentially attributable to the consumption of red wine. After nearly 20 years, several studies have investigated the fascinating, overwhelmingly positive biological and clinical associations of red wine consumption with cardiovascular disease and mortality. Light to moderate intake of red wine produces a kaleidoscope of potentially beneficial effects that target all phases of the atherosclerotic process, from atherogenesis (early plaque development and growth) to vessel occlusion (flow-mediated dilatation, thrombosis). Such beneficial effects involve cellular signaling mechanisms, interactions at the genomic level, and biochemical modifications of cellular and plasma components. Red wine components, especially alcohol, resveratrol, and other polyphenolic compounds, may decrease oxidative stress, enhance cholesterol efflux from vessel walls (mainly by increasing levels of high-density lipoprotein cholesterol), and inhibit lipoproteins oxidation, macrophage cholesterol accumulation, and foam-cell formation. These components may also increase nitric oxide bioavailability, thereby antagonizing the development of endothelial dysfunction, decrease blood viscosity, improve insulin sensitivity, counteract platelet hyperactivity, inhibit platelet adhesion to fibrinogen-coated surfaces, and decrease plasma levels of von Willebrand factor, fibrinogen, and coagulation factor VII. Light to moderate red wine consumption is also associated with a favorable genetic modulation of fibrinolytic proteins, ultimately increasing the surface-localized endothelial cell fibrinolysis. Overall, therefore, the "French paradox" may have its basis within a milieu containing several key molecules, so that favorable cardiovascular benefits might be primarily attributable to combined, additive, or perhaps synergistic effects of alcohol and other wine components on atherogenesis, coagulation, and fibrinolysis. Conversely, chronic heavy alcohol consumption and binge drinking are associated with increased risk of cardiovascular events. In conclusion, although mounting evidence strongly supports beneficial cardiovascular effects of moderate red wine consumption (one to two drinks per day; 10-30 g alcohol) in most populations, clinical advice to abstainers to initiate daily alcohol consumption has not yet been substantiated in the literature and must be considered with caution on an individual basis.

The myth and reality of Gray's paradox: implication of dolphin drag reduction for technology.

PubMed

Fish, Frank E

2006-06-01

The inconsistency for the calculated high drag on an actively swimming dolphin and underestimated muscle power available resulted in what has been termed Gray's paradox. Although Gray's paradox was flawed, it has been the inspiration for a variety of drag reduction mechanisms. This review examines the present state of knowledge of drag reduction specific to dolphins. Streamlining and special behaviors provide the greatest drag reduction for dolphins. Mechanisms to control flow by maintaining a completely laminar boundary layer over the body have not been demonstrated for dolphins.

Trends in added sugar supply and consumption in Australia: there is an Australian Paradox.

PubMed

Barclay, Alan W; Brand-Miller, Jennie C

2013-09-30

In 2011, Barclay and Brand-Miller reported the observation that trends in refined sugar consumption in Australia were the inverse of trends in overweight and obesity (The Australian Paradox). Rikkers et al. claim that the Australian Paradox is based on incomplete data because the sources utilised did not incorporate estimates for imported processed foods. This assertion is incorrect. Indeed, national nutrition surveys, sugar consumption data from the United Nations Food and Agricultural Organisation, the Australian Bureau of Statistics and Australian beverage industry data all incorporated data on imported products.

Spontaneous activity of single neurones in the hypothalamus of rabbits during sleep and waking

PubMed Central

Findlay, Alan L. R.; Hayward, James N.

1969-01-01

1. A method is described for recording from single cells in the hypothalamus of unanaesthetized freely moving rabbits. Behaviour, bodily movement, skin and brain temperatures and e.e.g. were monitored. 2. Patterns of unit firing during slow sleep, paradoxical sleep and waking were studied in several regions of the hypothalamus, thalamus and in the septum. 3. Of the 144 cells analysed from waking to slow sleep, fifty-six (39%) decreased mean firing rates, thirty (21%) increased spike discharges and fifty-eight (40%) showed no marked change. Dorsal hypothalamic and massa intermedia thalamic cells fired in brief high frequency clusters during slow sleep with a characteristic `bimodal' interspike interval histogram. Waking and paradoxical sleep abolished these cluster discharges with a concomitant change to an `asymmetric' histogram. 4. Of the thirty-two cells observed during the three states of waking, slow sleep and paradoxical sleep, a majority (twenty-five or 78%) showed their highest rates of spontaneous discharge during paradoxical sleep. Discharge rates of cells sometimes changed in the course of paradoxical sleep according to the presence or absence of phasic events such as myoclonic motor activity. Two hypothalmic cells were almost totally arrested during paradoxical sleep. 5. Analysis of unit firing rates during spontaneous rises in brain temperature during waking and paradoxical sleep revealed that a majority of the neurones (22/24) changed their discharge rates in relation to behaviour rather than to brain temperature. Two cells did appear to respond specifically to the central thermal stimulus. 6. Hypothalamic cells do not behave as a homogeneous population in relation to changes in the state of arousal of the rabbit. Spontaneous changes in cell discharge related to sleep-waking behaviour must be considered in any interpretation of hypothalamic unit activity as related to neuroendocrine or autonomic mechanisms. PMID:4304342

Exploring the isopycnal mixing and helium-heat paradoxes in a suite of Earth System Models

NASA Astrophysics Data System (ADS)

Gnanadesikan, A.; Abernathey, R.; Pradal, M.-A.

2014-11-01

This paper uses a suite of Earth System models which simulate the distribution of He isotopes and radiocarbon to examine two paradoxes in Earth science. The helium-heat paradox refers to the fact that helium emissions to the deep ocean are far lower than would be expected given the rate of geothermal heating, since both are thought to be the result of radioactive decay in the earth's interior. The isopycnal mixing paradox comes from the fact that many theoretical parameterizations of the isopycnal mixing coefficient ARedi that link it to baroclinic instability project it to be small (of order a few hundred m2 s-1) in the ocean interior away from boundary currents. However, direct observations using tracers and floats (largely in the upper ocean) suggest that values of this coefficient are an order of magnitude higher. Because helium isotopes equilibrate rapidly with the atmosphere, but radiocarbon equilibrates slowly, it might be thought that resolving the isopycnal mixing paradox in favor of the higher observational estimates of ARedi might also solve the helium paradox. In this paper we show that this is not the case. In a suite of models with different spatially constant and spatially varying values of ARedi the distribution of radiocarbon and helium isotopes is sensitive to the value of ARedi. However, away from strong helium sources in the Southeast Pacific, the relationship between the two is not sensitive, indicating that large-scale advection is the limiting process for removing helium and radiocarbon from the deep ocean. The helium isotopes, in turn, suggest a higher value of ARedi in the deep ocean than is seen in theoretical parameterizations based on baroclinic growth rates. We argue that a key part of resolving the isopycnal mixing paradox is to abandon the idea that ARedi has a direct relationship to local baroclinic instability and to the so called "thickness" mixing coefficient AGM.

A Resolution of the Paradox of Enrichment

NASA Astrophysics Data System (ADS)

Feng, Z. C.; Li, Y. Charles

2015-06-01

The paradox of enrichment was observed by Rosenzweig [1971] in a class of predator-prey models. Two of the parameters in the models are crucial for the paradox. These two parameters are the prey's carrying capacity and prey's half-saturation for predation. Intuitively, increasing the carrying capacity due to enrichment of the prey's environment should lead to a more stable predator-prey system. Analytically, it turns out that increasing the carrying capacity always leads to an unstable predator-prey system that is susceptible to extinction from environmental random perturbations. This is the so-called paradox of enrichment. Our resolution here rests upon a closer investigation on a dimensionless number H formed from the carrying capacity and the prey's half-saturation. By recasting the models into dimensionless forms, the models are in fact governed by a few dimensionless numbers including H. The effects of the two parameters: carrying capacity and half-saturation are incorporated into the number H. In fact, increasing the carrying capacity is equivalent (i.e. has the same effect on H) to decreasing the half-saturation which implies more aggressive predation. Since there is no paradox between more aggressive predation and instability of the predator-prey system, the paradox of enrichment is resolved. The so-called instability of the predator-prey system is characterized by the existence of a stable limit cycle in the phase plane, which gets closer and closer to the predator axis and prey axis. Due to random environmental perturbations, this can lead to extinction. We also further explore spatially dependent models for which the phase space is infinite-dimensional. The spatially independent limit cycle which is generated by a Hopf bifurcation from an unstable steady state, is linearly stable in the infinite-dimensional phase space. Numerical simulations indicate that the basin of attraction of the limit cycle is riddled. This shows that spatial perturbations can sometimes (neither always nor never) remove the paradox of enrichment near the limit cycle!

Students learning from patients: let's get real in medical education.

PubMed

Bleakley, Alan; Bligh, John

2008-03-01

Medical students must be prepared for working in inter-professional and multi-disciplinary clinical teams centred on a patient's care pathway. While there has been a good deal of rhetoric surrounding patient-centred medical education, there has been little attempt to conceptualise such a practice beyond the level of describing education of communication skills and empathy within a broad 'professionalism' framework. Paradoxically, while aiming to strengthen patient-student interactions, this approach tends to refocus on the role modelling of the physician, and opportunities for potentially deep collaborative working relationships between students and patients are missed. A radical overhaul of conventional doctor-led medical education may be necessary, that also challenges the orthodoxies of individualistic student-centred approaches, leading to an authentic patient-centred model that shifts the locus of learning from the relationship between doctor as educator and student to the relationship between patient and student, with expert doctor as resource. Drawing on contemporary poststructuralist theory of text and identity construction, and on innovative models of work-based learning, the potential quality of relationship between student and patient is articulated in terms of collaborative knowledge production, involving close reading with the patient as text, through dialogue. Here, a medical 'education' displaces traditional forms of medical 'training' that typically involve individual information reproduction. Students may, paradoxically, improve clinical acumen through consideration of silences, gaps, and contradictions in patients as texts, rather than treating communication as transparent. Such paradoxical effects have been systematically occluded or denied in traditional medical education.

Paradoxical correlation between signal in functional magnetic resonance imaging and deoxygenated haemoglobin content in capillaries: a new theoretical explanation

NASA Astrophysics Data System (ADS)

Yamamoto, Toru; Kato, Toshinori

2002-04-01

Signal increases in functional magnetic resonance imaging (fMRI) are believed to be a result of decreased paramagnetic deoxygenated haemoglobin (deoxyHb) content in the neural activation area. However, discrepancies in this canonical blood oxygenation level dependent (BOLD) theory have been pointed out in studies using optical techniques, which directly measure haemoglobin changes. To explain the discrepancies, we developed a new theory bridging magnetic resonance (MR) signal and haemoglobin changes. We focused on capillary influences, which have been neglected in most previous fMRI studies and performed a combined fMRI and near-infrared spectroscopy (NIRS) study using a language task. Paradoxically, both the MR signal and deoxyHb content increased in Broca's area. On the other hand, fMRI activation in the auditory area near large veins correlated with a mirror-image decrease in deoxyHb and increase in oxygenated haemoglobin (oxyHb), in agreement with canonical BOLD theory. All fMRI signal changes correlated consistently with changes in oxyHb, the diamagnetism of which is insensitive to MR. We concluded that the discrepancy with the canonical BOLD theory is caused by the fact that the BOLD theory ignores the effect of the capillaries. Our theory explains the paradoxical phenomena of the oxyHb and deoxyHb contributions to the MR signal and gives a new insight into the precise haemodynamics of activation by analysing fMRI and NIRS data.

High Agreement and High Prevalence: The Paradox of Cohen's Kappa.

PubMed

Zec, Slavica; Soriani, Nicola; Comoretto, Rosanna; Baldi, Ileana

2017-01-01

Cohen's Kappa is the most used agreement statistic in literature. However, under certain conditions, it is affected by a paradox which returns biased estimates of the statistic itself. The aim of the study is to provide sufficient information which allows the reader to make an informed choice of the correct agreement measure, by underlining some optimal properties of Gwet's AC1 in comparison to Cohen's Kappa, using a real data example. During the process of literature review, we have asked a panel of three evaluators to come up with a judgment on the quality of 57 randomized controlled trials assigning a score to each trial using the Jadad scale. The quality was evaluated according to the following dimensions: adopted design, randomization unit, type of primary endpoint. With respect to each of the above described features, the agreement between the three evaluators has been calculated using Cohen's Kappa statistic and Gwet's AC1 statistic and, finally, the values have been compared with the observed agreement. The values of the Cohen's Kappa statistic would lead to believe that the agreement levels for the variables Unit, Design and Primary Endpoints are totally unsatisfactory. The AC1 statistic, on the contrary, shows plausible values which are in line with the respective values of the observed concordance. We conclude that it would always be appropriate to adopt the AC1 statistic, thus bypassing any risk of incurring the paradox and drawing wrong conclusions about the results of agreement analysis.

The immigrant paradox among Asian American women: are disparities in the burden of depression and anxiety paradoxical or explicable?

PubMed

Lau, Anna S; Tsai, William; Shih, Josephine; Liu, Lisa L; Hwang, Wei-Chin; Takeuchi, David T

2013-10-01

We evaluated potential explanations for advantaged mental health status among immigrant Asian American women compared to U.S.-born Asian American women. In a nationally representative sample of 1,030 women (185 U.S.-born, 368 early-life immigrants [arrived before 25 years of age], 477 late-life immigrants), we examined the hypothesis that increased exposure to social risk factors mediate nativity-based differences in lifetime prevalence of depression and anxiety disorders. Indicators of social class were also examined as protective factors enjoyed by U.S.-born women that may suppress observed nativity-based disparities. We also examined whether there were group differences in reactivity to stress in predicting disorder. U.S.-born women were twice as likely as late-life immigrants to report lifetime history of depression (odds ratio [OR] = 2.03, 95% CI [1.35, 4.54]) and anxiety (OR = 2.12, 95% CI [1.34, 5.19]). Nativity differences in perceived discrimination, family conflict, and cultural conflict explained disparities in rates of disorder. There was no support for the contention that immigrant women were more psychologically hardy or resilient to social stress. Findings suggest that the gap in mental health status between U.S.- and foreign-born Asian American women would indeed be magnified if differences in social status were accounted for, but also that ready explanations for the so-called immigrant paradox are found in differential levels of reported stress exposure. (c) 2013 APA, all rights reserved.

The social dominance paradox.

PubMed

Cook, Jennifer Louise; den Ouden, Hanneke E M; Heyes, Cecilia M; Cools, Roshan

2014-12-01

Dominant individuals report high levels of self-sufficiency, self-esteem, and authoritarianism. The lay stereotype suggests that such individuals ignore information from others, preferring to make their own choices. However, the nonhuman animal literature presents a conflicting view, suggesting that dominant individuals are avid social learners, whereas subordinates focus on learning from private experience. Whether dominant humans are best characterized by the lay stereotype or the animal view is currently unknown. Here, we present a "social dominance paradox": using self-report scales and computerized tasks, we demonstrate that socially dominant people explicitly value independence, but, paradoxically, in a complex decision-making task, they show an enhanced reliance (relative to subordinate individuals) on social learning. More specifically, socially dominant people employed a strategy of copying other agents when the agents' responses had a history of being correct. However, in humans, two subtypes of dominance have been identified: aggressive and social. Aggressively dominant individuals, who are as likely to "get their own way" as socially dominant individuals but who do so through the use of aggressive or Machiavellian tactics, did not use social information, even when it was beneficial to do so. This paper presents the first study of dominance and social learning in humans and challenges the lay stereotype in which all dominant individuals ignore others' views. The more subtle perspective we offer could have important implications for decision making in both the boardroom and the classroom. Copyright © 2014 Elsevier Ltd. All rights reserved.

On Johnson's Paradox: Hypothesis Verification

ERIC Educational Resources Information Center

Noble, Clyde E.

1975-01-01

When H. M. Johnson argued that all inductive reasoning is based on the fallacy of affirming the consequent and cannot therefore establish the 'truth' of scientific hypotheses, he posed a paradox for strict empiricists. Author examined Johnson's argument. (Editor/RK)

A Paradox About Excellence of Schools and the People in them

ERIC Educational Resources Information Center

Glass, Gene V.

1975-01-01

Three reactions to the paradox in question are given. Generally, some evaluation feedback is considered to hurt more than help, but more often than not evaluations can provide direction and guidance to educators. (AM)

Perspectives on Games, Computers, and Mental Health: Questions about Paradoxes, Evidences, and Challenges.

PubMed

Desseilles, Martin

2016-01-01

In the field of mental health, games and computerized games present questions about paradoxes, evidences, and challenges. This perspective article offers perspectives and personal opinion about these questions, evidences, and challenges with an objective of presenting several ideas and issues in this rapidly developing field. First, games raise some questions in the sense of the paradox between a game and an issue, as well as the paradox of using an amusing game to treat a serious pathology. Second, games also present evidence in the sense that they involve relationships with others, as well as learning, communication, language, emotional regulation, and hedonism. Third, games present challenges, such as the risk of abuse, the critical temporal period that may be limited to childhood, their important influence on sociocognitive learning and the establishment of social norms, and the risk of misuse of games.

Paradoxical undressing associated with subarachnoid hemorrhage in a non-hypothermia case?

PubMed

Descloux, Emilienne; Ducrot, Kewin; Scarpelli, Maria Pia; Lobrinus, Alexander; Palmiere, Cristian

2017-09-01

Paradoxical undressing is a phenomenon characterizing some fatal hypothermia cases. The victims, despite low environmental temperatures, paradoxically remove their clothes due to a sudden feeling of warmth. In this report, we describe a case of suspected paradoxical undressing in a non-hypothermia case. The victim, a 51-year-old Caucasian man, was found dead wearing only sneakers and socks. All other clothing was found in his car. Postmortem investigations allowed the hypothesis of hypothermia to be ruled out and revealed the presence of a ruptured cerebral aneurysm that caused a subarachnoid hemorrhage, the latter responsible for the death. The absence of any elements suggesting a voluntary undressing or any third party's DNA profile or involvement along with the possibility that the subarachnoid hemorrhage might have determined a hypothalamic injury, somehow rendered conceivable the hypothesis of an inappropriate feeling of warmth due to hemorrhage-induced dysregulation of the hypothalamic temperature-regulating centers.

The ethical use of paradoxical interventions in psychotherapy.

PubMed Central

Foreman, D M

1990-01-01

The purpose of this paper is to establish ethical guidelines for the use of paradoxical interventions in psychotherapy. These are defined as interventions which are counterintuitive, coercive, and which require non-observance by the client. Arguments are developed to show that such interventions are associated with a psychology that understands individuals solely in terms of their relationship: a 'strong interactionist' position. Ethical principles consistent with such a position are considered, and from these it is derived that: paradox is an ethical technique with resistive patients; it requires consent; its content should be consistent with general ethical principles, especially those of beneficence and non-maleficence; non-paradoxical techniques should be preferred when possible; and it should not be used as an assessment procedure. It is concluded that research is needed to explore the effect of such ethical guidelines of effectiveness, though preliminary impressions are encouraging. PMID:2287016

Perspectives on Games, Computers, and Mental Health: Questions about Paradoxes, Evidences, and Challenges

PubMed Central

Desseilles, Martin

2016-01-01

In the field of mental health, games and computerized games present questions about paradoxes, evidences, and challenges. This perspective article offers perspectives and personal opinion about these questions, evidences, and challenges with an objective of presenting several ideas and issues in this rapidly developing field. First, games raise some questions in the sense of the paradox between a game and an issue, as well as the paradox of using an amusing game to treat a serious pathology. Second, games also present evidence in the sense that they involve relationships with others, as well as learning, communication, language, emotional regulation, and hedonism. Third, games present challenges, such as the risk of abuse, the critical temporal period that may be limited to childhood, their important influence on sociocognitive learning and the establishment of social norms, and the risk of misuse of games. PMID:27458390

The paradox of enrichment in an adaptive world

PubMed Central

Mougi, Akihiko; Nishimura, Kinya

2008-01-01

Paradoxically, enrichment can destabilize a predator–prey food web. While adaptive dynamics can greatly influence the stability of interaction systems, few theoretical studies have examined the effect of the adaptive dynamics of interaction-related traits on the possibility of resolution of the paradox of enrichment. We consider the evolution of attack and defence traits of a predator and two prey species in a one predator–two prey system in which the predator practises optimal diet use. The results showed that optimal foraging alone cannot eliminate a pattern of destabilization with enrichment, but trait evolution of the predator or prey can change the pattern to one of stabilization, implying a possible resolution of the paradox of enrichment. Furthermore, trait evolution in all species can broaden the parameter range of stabilization. Importantly, rapid evolution can stabilize this system, but weaken its stability in the face of enrichment. PMID:18700201

Einstein-Podolsky-Rosen paradox in single pairs of images.

PubMed

Lantz, Eric; Denis, Séverine; Moreau, Paul-Antoine; Devaux, Fabrice

2015-10-05

Spatially entangled twin photons provide a test of the Einstein-Podolsky-Rosen (EPR) paradox in its original form of position (image plane) versus impulsion (Fourier plane). We show that recording a single pair of images in each plane is sufficient to safely demonstrate an EPR paradox. On each pair of images, we have retrieved the fluctuations by subtracting the fitted deterministic intensity shape and then have obtained an intercorrelation peak with a sufficient signal to noise ratio to safely distinguish this peak from random fluctuations. A 95% confidence interval has been determined, confirming a high degree of paradox whatever the considered single pairs. Last, we have verified that the value of the variance of the difference between twin images is always below the quantum (poissonian) limit, in order to ensure the particle character of the demonstration. Our demonstration shows that a single image pattern can reveal the quantum and non-local behavior of light.

Single Molecule Study of DNA Organization and Recombination

NASA Astrophysics Data System (ADS)

Xiao, Botao

We have studied five projects related to DNA organization and recombination using mainly single molecule force-spectroscopy and statistical tools. First, HU is one of the most abundant DNA-organizing proteins in bacterial chromosomes and participates in gene regulation. We report experiments that study the dependence of DNA condensation by HU on force, salt and HU concentration. A first important result is that at physiological salt levels, HU only bends DNA, resolving a previous paradox of why a chromosome-compacting protein should have a DNA-stiffening function. A second major result is quantitative demonstration of strong dependencies of HU-DNA dissociation on both salt concentration and force. Second, we have used a thermodynamic Maxwell relation to count proteins driven off large DNAs by tension, an effect important to understanding DNA organization. Our results compare well with estimates of numbers of proteins HU and Fis in previous studies. We have also shown that a semi-flexible polymer model describes our HU experimental data well. The force-dependent binding suggests mechano-chemical mechanisms for gene regulation. Third, the elusive role of protein H1 in chromatin has been clarified with purified H1 and Xenopus extracts. We find that H1 compacts DNA by both bending and looping. Addition of H1 enhances chromatin formation and maintains the plasticity of the chromatin. Fourth, the topology and mechanics of DNA twisting are critical to DNA organization and recombination. We have systematically measured DNA extension as a function of linking number density from 0.08 to -2 with holding forces from 0.2 to 2.4 pN. Unlike previous proposals, the DNA extension decreases with negative linking number. Finally, DNA recombination is a dynamic process starting from enzyme-DNA binding. We report that the Int-DBD domain of lambda integrase binds to DNA without compaction at low Int-DBD concentration. High concentration of Int-DBD loops DNA below a threshold force, which depends on salt concentration. We also report experiments with the recombinase Hin mutant H107Y. The synapse formation is demonstrated with single DNA containing two hix sites. We further show preliminary data for cleavage and subunit rotation from a braiding assay. These direct observations elucidate the recombination mechanism.

Regional magnetic and gravity features of the Gibson Dome area and surrounding region, Paradox Basin, Utah : a preliminary report

USGS Publications Warehouse

Hildenbrand, T.G.; Kucks, R.P.

1983-01-01

Analyses of regional gravity and magnetic anomaly maps have been carried out to assist in the evaluation of the Gibson Dome area as a possible repository site for high-level radioactive waste. Derivative, wavelength-filtered, and trend maps were compiled to aid in properly locating major geophysical trends corresponding to faults, folds, and lithologic boundaries. The anomaly maps indicate that Paradox Basin is characterized by a heterogeneous Precambrian basement, essentially a metamorphic complex of gneisses and schist intruded by granitic rocks and mafic to ultramafic bodies. Interpreted Precambrian structures trend predominantly northwest and northeast although east-west trending features are evident. Prominent gravity lows define the salt anticlines. Structural and lithologic trends in the Gibson Dome area are closely examined. Of greatest interest is a series of circular magnetic highs trending west-northwest into the Gibson Dome area. Further study of the exact definition and geologic significance of this series of anomalies is warranted.

The art of seeing and painting.

PubMed

Grossberg, Stephen

2008-01-01

The human urge to represent the three-dimensional world using two-dimensional pictorial representations dates back at least to Paleolithic times. Artists from ancient to modern times have struggled to understand how a few contours or color patches on a flat surface can induce mental representations of a three-dimensional scene. This article summarizes some of the recent breakthroughs in scientifically understanding how the brain sees that shed light on these struggles. These breakthroughs illustrate how various artists have intuitively understood paradoxical properties about how the brain sees, and have used that understanding to create great art. These paradoxical properties arise from how the brain forms the units of conscious visual perception; namely, representations of three-dimensional boundaries and surfaces. Boundaries and surfaces are computed in parallel cortical processing streams that obey computationally complementary properties. These streams interact at multiple levels to overcome their complementary weaknesses and to transform their complementary properties into consistent percepts. The article describes how properties of complementary consistency have guided the creation of many great works of art.

Cannabis and sex: multifaceted paradoxes.

PubMed

Cohen, S

1982-01-01

At the present level of ignorance about sexuality and cannabis, what rational position can be adopted? First, it must be recognized that even without cannabis, current involvement in sex-related activities may well have been called "promiscuous" by a preceding generation or two. The general loosening of morality, the erosion of family, church and other authoritarian controls, The Pill, antibiotics and other recent developments have contributed to current casual attitudes. Although one may not perceive it, counterculture beliefs have had their impact on the dominant culture. Marijuana has some enhancing effect upon sexual proceedings for some individuals. It may be sexually evocative and gratifying. Nonspecific factors play an important role in this matter. Opposite effects also occur, and an endocrinologic basis for actual diminution of drives and potency may exist. The final paradox is that cannabis' employment for sexual arousal is predominantly an activity of young adults. The older age groups most in need of sexual support and assistance are less frequently involved in its use. It is unclear why this dichotomy between need and utilization exists.

Proteomics Unveils Fibroblast-Cardiomyocyte Lactate Shuttle and Hexokinase Paradox in Mouse Muscles.

PubMed

Rakus, Dariusz; Gizak, Agnieszka; Wiśniewski, Jacek R

2016-08-05

Quantitative mapping, given in biochemically interpretable units such as mol per mg of total protein, of tissue-specific proteomes is prerequisite for the analysis of any process in cells. We applied label- and standard-free proteomics to characterize three types of striated muscles: white, red, and cardiac muscle. The analysis presented here uncovers several unexpected and novel features of striated muscles. In addition to differences in protein expression levels, the three muscle types substantially differ in their patterns of basic metabolic pathways and isoforms of regulatory proteins. Importantly, some of the conclusions drawn on the basis of our results, such as the potential existence of a "fibroblast-cardiomyocyte lactate shuttle" and the "hexokinase paradox" point to the necessity of reinterpretation of some basic aspects of striated muscle metabolism. The data presented here constitute a powerful database and a resource for future studies of muscle physiology and for the design of pharmaceutics for the treatment of muscular disorders.

What the cerveau isolé preparation tells us nowadays about sleep-wake mechanisms?

PubMed

Gottesmann, C

1988-01-01

The intercollicular transected preparation opened a rich field for investigations of sleep-wake mechanisms. Initial results showed that brain stem ascending influences are essential for maintaining an activated cortex. It was subsequently shown that the forebrain also develops activating influences, since EEG desynchronization of the cortex reappears in the chronic cerveau isolé preparation, and continuous or almost continuous theta rhythm is able to occur in the acute cerveau isolé preparation. A brief "intermediate stage" of sleep occurs during natural sleep just prior to and after paradoxical sleep. It is characterized by cortical spindle bursts, hippocampal low frequency theta activity (two patterns of the acute cerveau isolé preparation) and is accompanied by a very low thalamic transmission level, suggesting a cerveau isolé-like state. The chronic cerveau isolé preparation also demonstrates that the executive processes of paradoxical sleep are located in the lower brain stem, while the occurrence of this sleep stage seems to be modulated by forebrain structures.

The IL-6 Paradox: Context Dependent Interplay of SOCS3 and AMPK

PubMed Central

Sarvas, Jessica L; Khaper, Neelam; Lees, Simon J

2013-01-01

Insulin resistance is the principle step towards the progression of type 2 diabetes, and has been linked to increased circulating levels of cytokines, leading to chronic low-grade inflammation. Specifically, in chronic disease states increased IL-6 is thought to play a critical role in the regulation of insulin resistance in the peripheral tissues, and has been used as a marker of insulin resistance. There is also an endogenous up-regulation of IL-6 in response to exercise, which has been linked to improved insulin sensitivity. This leads to the question “how can elevated IL-6 lead to the development of insulin resistance, and yet also lead to increased insulin sensitivity?” Resolving the dual role of IL-6 in regulating insulin resistance/sensitivity is critical to the development of potential therapeutic interventions. This review summarizes the literature on the seemingly paradoxical role of elevated IL-6 on insulin signalling, including the activation of AMPK and the involvement of leptin and SOCS3. PMID:24244888

“At times, I feel like I’m sinning”: The paradoxical role of non-LGBT-affirming religion in the lives of behaviourally bisexual Latino men

PubMed Central

Severson, Nicolette; Muñoz-Laboy, Miguel; Kaufman, Rebecca

2015-01-01

In this paper we examine non-LGBT-affirming religiosity among behaviourally bisexual Latino men as it relates to sexual attitudes, experiences, and behaviours. We asked, how does religiosity correspond to masculine identities, sex roles, and condom efficacy? And, how might religiosity influence contexts of health risks? Data was analysed from a mixed-methods study of 142 behaviourally bisexual Latino men, aged 18–60 years. Major findings included positive correlations between religiosity and a) masculine ideologies, b) internalised homonegativity, c) less comfort with receptive sex, d) low condom efficacy, and e) higher levels of loneliness and incidents of discriminatory events. Results are paired with illustrative, descriptive case studies from life history interviews. It is suggested that non-LGBT-affirming religiosity plays a paradoxical role in the lives of behaviourally bisexual Latino men: on one hand, increasing internalised homonegativity and attendant health risks; on the other, providing social support to members of a marginalised population. PMID:24261850

"Macho men" and preventive health care: implications for older men in different social classes.

PubMed

Springer, Kristen W; Mouzon, Dawne M

2011-06-01

The gender paradox in mortality--where men die earlier than women despite having more socioeconomic resources--may be partly explained by men's lower levels of preventive health care. Stereotypical notions of masculinity reduce preventive health care; however, the relationship between masculinity, socioeconomic status (SES), and preventive health care is unknown. Using the Wisconsin Longitudinal Study, the authors conduct a population-based assessment of masculinity beliefs and preventive health care, including whether these relationships vary by SES. The results show that men with strong masculinity beliefs are half as likely as men with more moderate masculinity beliefs to receive preventive care. Furthermore, in contrast to the well-established SES gradient in health, men with strong masculinity beliefs do not benefit from higher education and their probability of obtaining preventive health care decreases as their occupational status, wealth, and/or income increases. Masculinity may be a partial explanation for the paradox of men's lower life expectancy, despite their higher SES.

Dominant Alcohol-Protein Interaction via Hydration-Enabled Enthalpy-Driven Binding Mechanism

PubMed Central

Chong, Yuan; Kleinhammes, Alfred; Tang, Pei; Xu, Yan; Wu, Yue

2015-01-01

Water plays an important role in weak associations of small drug molecules with proteins. Intense focus has been on binding-induced structural changes in the water network surrounding protein binding sites, especially their contributions to binding thermodynamics. However, water is also tightly coupled to protein conformations and dynamics, and so far little is known about the influence of water-protein interactions on ligand binding. Alcohols are a type of low-affinity drugs, and it remains unclear how water affects alcohol-protein interactions. Here, we present alcohol adsorption isotherms under controlled protein hydration using in-situ NMR detection. As functions of hydration level, Gibbs free energy, enthalpy, and entropy of binding were determined from the temperature dependence of isotherms. Two types of alcohol binding were found. The dominant type is low-affinity nonspecific binding, which is strongly dependent on temperature and the level of hydration. At low hydration levels, this nonspecific binding only occurs above a threshold of alcohol vapor pressure. An increased hydration level reduces this threshold, with it finally disappearing at a hydration level of h~0.2 (g water/g protein), gradually shifting alcohol binding from an entropy-driven to an enthalpy-driven process. Water at charged and polar groups on the protein surface was found to be particularly important in enabling this binding. Although further increase in hydration has smaller effects on the changes of binding enthalpy and entropy, it results in significant negative change in Gibbs free energy due to unmatched enthalpy-entropy compensation. These results show the crucial role of water-protein interplay in alcohol binding. PMID:25856773

How Does the Ca2+-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca2+ Dynamics and Cell Structures in Perfused Rat Hearts—

PubMed Central

Mani, Hiroki; Tanaka, Hideo; Adachi, Tetsuya; Ikegawa, Masaya; Dai, Ping; Fujita, Naohisa; Takamatsu, Tetsuro

2015-01-01

The calcium (Ca2+)-paradox injury of the heart, induced by restoration of extracellular Ca2+ after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca2+-paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca2+ dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca2+ paradox. Under rapid-scanning confocal microscopy, repletion of Ca2+ following its depletion produced high-frequency Ca2+ waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl2, but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca2+ influx in the injury. However, saponin-induced membrane permeabilization of Ca2+ showed no apparent contracture despite the emergence of high-frequency Ca2+ waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca2+ paradox. In immunohistochemistry Ca2+ depletion produced separation of the intercalated disc that expresses cadherin and dissipation of β-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca2+ influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca2+-paradox injury. PMID:25861132

Public health policy paradoxes: science and politics in the Rockefeller Foundation's hookworm campaign in Mexico in the 1920s.

PubMed

Birn, A E; Solórzano, A

1999-11-01

The origins of US international health endeavors are intertwined with the Progressive Era's faith in science as arbiter of humankind's secular problems. No agency better exemplifies the period's confidence in science than the Rockefeller Foundation's International Health Board (IHB), which set out to export the new public health theory and practice around the world. An examination of the IHB's hookworm program in Mexico in the 1920s demonstrates that, notwithstanding the Rockefeller Foundation's (RF) self-conscious commitment to scientific neutrality, its programs continuously engaged political criteria, exhibiting the competition, coexistence, and inseparability of the worlds of science, politics, and international health policy. Analysis of the program's quotidian decisions and larger strategies further reveals the protean quality of RF science-politics, which enabled responses to parochial and broadly-conceived needs at multiple levels. In the focus on hookworm, the selection of campaign sites, hookworm diagnosis methods, treatment procedures, definition of cure, and the assignment of responsibility for prevention, scientific and political considerations were inextricably bound. The science-politics paradox was molded by the hookworm program's constituencies in Mexico, including political leaders, health bureaucrats, physicians, business interests, public health workers, peasants, and Rockefeller officers. The multiple, often contradictory, roles of the RF's hookworm campaign are characteristic of the policy paradoxes that emerge when science is summoned to drive policy. In Mexico the campaign served as a policy cauldron through which new knowledge could be demonstrated applicable to social and political problems on many levels. The repeated pledge of scientific neutrality belied the hookworm program's inherent aim of persuading government officials, the medical community, business interests, and the populace of the value of investing in public health as a means to improve social conditions, further a medical model of health and sickness, increase economic productivity, and promote good relations between the US and Mexico.

One-Piece Faraday Generator: A Paradoxical Experiment from 1851

ERIC Educational Resources Information Center

Crooks, M. J.; And Others

1978-01-01

Describes an experiment based on Faraday's one-piece generator, where the rotating disk is replaced by a cylindrical permanent magnet. Explains the apparent paradox that an observer in an inertial frame could measure his absolute velocity. (GA)

Stable centromere positioning in diverse sequence contexts of complex and satellite centromeres of maize and wild relatives.

PubMed

Gent, Jonathan I; Wang, Na; Dawe, R Kelly

2017-06-21

Paradoxically, centromeres are known both for their characteristic repeat sequences (satellite DNA) and for being epigenetically defined. Maize (Zea mays mays) is an attractive model for studying centromere positioning because many of its large (~2 Mb) centromeres are not dominated by satellite DNA. These centromeres, which we call complex centromeres, allow for both assembly into reference genomes and for mapping short reads from ChIP-seq with antibodies to centromeric histone H3 (cenH3). We found frequent complex centromeres in maize and its wild relatives Z. mays parviglumis, Z. mays mexicana, and particularly Z. mays huehuetenangensis. Analysis of individual plants reveals minor variation in the positions of complex centromeres among siblings. However, such positional shifts are stochastic and not heritable, consistent with prior findings that centromere positioning is stable at the population level. Centromeres are also stable in multiple F1 hybrid contexts. Analysis of repeats in Z. mays and other species (Zea diploperennis, Zea luxurians, and Tripsacum dactyloides) reveals tenfold differences in abundance of the major satellite CentC, but similar high levels of sequence polymorphism in individual CentC copies. Deviation from the CentC consensus has little or no effect on binding of cenH3. These data indicate that complex centromeres are neither a peculiarity of cultivation nor inbreeding in Z. mays. While extensive arrays of CentC may be the norm for other Zea and Tripsacum species, these data also reveal that a wide diversity of DNA sequences and multiple types of genetic elements in and near centromeres support centromere function and constrain centromere positions.

A Sterile 20 Family Kinase and Its Co-factor CCM-3 Regulate Contractile Ring Proteins on Germline Intercellular Bridges.

PubMed

Rehain-Bell, Kathryn; Love, Andrew; Werner, Michael E; MacLeod, Ian; Yates, John R; Maddox, Amy Shaub

2017-03-20

Germ cells in most animals are connected by intercellular bridges, actin-based rings that form stable cytoplasmic connections between cells promoting communication and coordination [1]. Moreover, these connections are required for fertility [1, 2]. Intercellular bridges are proposed to arise from stabilization of the cytokinetic ring during incomplete cytokinesis [1]. Paradoxically, proteins that promote closure of cytokinetic rings are enriched on stably open intercellular bridges [1, 3, 4]. Given this inconsistency, the mechanism of intercellular bridge stabilization is unclear. Here, we used the C. elegans germline as a model for identifying molecular mechanisms regulating intercellular bridges. We report that bridges are actually highly dynamic, changing size at precise times during germ cell development. We focused on the regulation of bridge stability by anillins, key regulators of cytokinetic rings and cytoplasmic bridges [1, 4-7]. We identified GCK-1, a conserved serine/threonine kinase [8], as a putative novel anillin interactor. GCK-1 works together with CCM-3, a known binding partner [9], to promote intercellular bridge stability and limit localization of both canonical anillin and non-muscle myosin II (NMM-II) to intercellular bridges. Additionally, we found that a shorter anillin, known to stabilize bridges [4, 7], also regulates NMM-II levels at bridges. Consistent with these results, negative regulators of NMM-II stabilize intercellular bridges in the Drosophila egg chamber [10, 11]. Together with our findings, this suggests that tuning of myosin levels is a conserved mechanism for the stabilization of intercellular bridges that can occur by diverse molecular mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Topography of sound level representation in the FM sweep selective region of the pallid bat auditory cortex.

PubMed

Measor, Kevin; Yarrow, Stuart; Razak, Khaleel A

2018-05-26

Sound level processing is a fundamental function of the auditory system. To determine how the cortex represents sound level, it is important to quantify how changes in level alter the spatiotemporal structure of cortical ensemble activity. This is particularly true for echolocating bats that have control over, and often rapidly adjust, call level to actively change echo level. To understand how cortical activity may change with sound level, here we mapped response rate and latency changes with sound level in the auditory cortex of the pallid bat. The pallid bat uses a 60-30 kHz downward frequency modulated (FM) sweep for echolocation. Neurons tuned to frequencies between 30 and 70 kHz in the auditory cortex are selective for the properties of FM sweeps used in echolocation forming the FM sweep selective region (FMSR). The FMSR is strongly selective for sound level between 30 and 50 dB SPL. Here we mapped the topography of level selectivity in the FMSR using downward FM sweeps and show that neurons with more monotonic rate level functions are located in caudomedial regions of the FMSR overlapping with high frequency (50-60 kHz) neurons. Non-monotonic neurons dominate the FMSR, and are distributed across the entire region, but there is no evidence for amplitopy. We also examined how first spike latency of FMSR neurons change with sound level. The majority of FMSR neurons exhibit paradoxical latency shift wherein the latency increases with sound level. Moreover, neurons with paradoxical latency shifts are more strongly level selective and are tuned to lower sound level than neurons in which latencies decrease with level. These data indicate a clustered arrangement of neurons according to monotonicity, with no strong evidence for finer scale topography, in the FMSR. The latency analysis suggests mechanisms for strong level selectivity that is based on relative timing of excitatory and inhibitory inputs. Taken together, these data suggest how the spatiotemporal spread of cortical activity may represent sound level. Copyright © 2018. Published by Elsevier B.V.

Hippocampal HDAC4 contributes to postnatal fluoxetine-evoked depression-like behavior.

PubMed

Sarkar, Ambalika; Chachra, Parul; Kennedy, Pamela; Pena, Catherine J; Desouza, Lynette A; Nestler, Eric J; Vaidya, Vidita A

2014-08-01

Fluoxetine treatment in adulthood evokes antidepressant and anxiolytic responses. Paradoxically, postnatal fluoxetine (PNFlx) induces persistent depression- and anxiety-like behaviors. The mechanistic underpinnings of this paradox remain poorly understood. Here, we examined specific molecular changes in the rat hippocampus that accompany perturbed emotionality observed across life following PNFlx. PNFlx-induced hippocampal gene regulation observed in microarray and quantitative PCR studies indicate functional enrichment of genes involved in response to organic substances, protein kinase pathways, DNA binding, and transcriptional repression. We noted specific transcripts (Hdac4, mammalian target of rapamycin (mTOR), Gnai1, protein kinase C gamma (Prkcc), and hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1)) that were consistently dysregulated across life, and selectively influenced by postnatal, but not adult, fluoxetine. Increased histone deacetylase-4 (HDAC4) recruitment, accompanied by decreased activating histone acetylation marks at the mTOR and Gnai1 promoters, indicate a role for HDAC4 in PNFlx-mediated gene dysregulation. Strikingly, coadministration of the HDAC inhibitor sodium butyrate with PNFlx prevented the dysregulation of Hdac4 and mTOR, and the emergence of depression- and anxiety-like behavior. Importantly, we also find that retreatment of PNFlx animals with fluoxetine in adulthood reversed the increased Hdac4 expression, prevented HDAC4 recruitment to the mTOR and Gnai1 promoters, and attenuated the decline in mTOR and Gnai1 expression, coincident with normalization of PNFlx-evoked depression- and anxiety-like behavior. Further, we show that viral-mediated hippocampal overexpression of Hdac4 was sufficient to induce depression-, but not anxiety-, like behavior in adulthood. Our results highlight the unique nature of molecular signatures evoked by PNFlx, and implicate HDAC4 in the dysregulated gene expression and emergence of perturbed emotionality following fluoxetine exposure in early life.

Interactions between Ibrutinib and Anti-CD20 Antibodies: Competing Effects on the Outcome of Combination Therapy.

PubMed

Skarzynski, Martin; Niemann, Carsten U; Lee, Yuh Shan; Martyr, Sabrina; Maric, Irina; Salem, Dalia; Stetler-Stevenson, Maryalice; Marti, Gerald E; Calvo, Katherine R; Yuan, Constance; Valdez, Janet; Soto, Susan; Farooqui, Mohammed Z H; Herman, Sarah E M; Wiestner, Adrian

2016-01-01

Clinical trials of ibrutinib combined with anti-CD20 monoclonal antibodies (mAb) for chronic lymphocytic leukemia (CLL) report encouraging results. Paradoxically, in preclinical studies, in vitro ibrutinib was reported to decrease CD20 expression and inhibit cellular effector mechanisms. We therefore set out to investigate effects of in vivo ibrutinib treatment that could explain this paradox. Patients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial. Serial blood samples were collected pretreatment and during treatment for ex vivo functional assays to examine the effects on CLL cell susceptibility to anti-CD20 mAbs. We demonstrate that CD20 expression on ibrutinib was rapidly and persistently downregulated (median reduction 74%, day 28, P < 0.001) compared with baseline. Concomitantly, CD20 mRNA was decreased concurrent with reduced NF-κB signaling. An NF-κB binding site in the promoter of MS4A1 (encoding CD20) and downregulation of CD20 by NF-κB inhibitors support a direct transcriptional effect. Ex vivo, tumor cells from patients on ibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pretreatment cells (median reduction 75%, P < 0.001); however, opsonization by the complement protein C3d, which targets cells for phagocytosis, was relatively maintained. Expression of decay-accelerating factor (CD55) decreased on ibrutinib, providing a likely mechanism for the preserved C3d opsonization. In addition, ibrutinib significantly inhibited trogocytosis, a major contributor to antigen loss and tumor escape during mAb therapy. Our data indicate that ibrutinib promotes both positive and negative interactions with anti-CD20 mAbs, suggesting that successfully harnessing maximal antitumor effects of such combinations requires further investigation. ©2015 American Association for Cancer Research.

The Hydrostatic Paradox.

ERIC Educational Resources Information Center

Wilson, Alpha E.

1995-01-01

Presents an example demonstrating the quantitative resolution of the hydrostatic paradox which is the realization that the force due to fluid pressure on the bottom of a vessel can be considerably greater or considerably less than the weight of the fluid in the vessel. (JRH)

Resolving the biodiversity paradox

Treesearch

James S. Clark; Mike Dieta; Sukhendu Chakraborty; Pankaj K.Ibeanez Agarwal; Shannon LaDeau; Mike Wolosin

2007-01-01

The paradox of biodiversity involves three elements, (i) mathematical models predict that species must differ in specific ways in order to coexist as stable ecological communities, (ii) such differences are difficult to identify, yet (iii) there is widespread evidence of stability in natural communities.

How Much Do Minority Lives Matter?

ERIC Educational Resources Information Center

Witmer, Jeff

2015-01-01

There are many well-known data sets that can be used to illustrate Simpson's Paradox. The Stand Your Ground data presented here shows Simpson's Paradox. In these data, race plays the key role--and not in the way that some students expect.

The Paradox of Ingestion of Dietary Cholesterol in "Vegans"-Reply.

PubMed

Clarys, Peter; Deliens, Tom; Huybrechts, Inge; Deriemaeker, Peter; Vanaelst, Barbara; De Keyzer, Willem; Hebbelinck, Marcel; Mullie, Patrick

2017-07-21

In a comment on several articles on the vegan dietary pattern, Antoniazzi & Acosta-Navarro (2017) mentioned the paradox of the presence of dietary cholesterol as a nutritional component in the analysis of the vegan dietary pattern [1]. [...].

Setting Standards: Confronting Paradox.

ERIC Educational Resources Information Center

Doecke, Brenton; Gill, Margaret

2001-01-01

Discusses implications of the issues of continuity and discontinuity, commonality and difference, congruity and paradox as they engage the research team, the industry partners, and the teachers around Australia who constitute the STELLA (Standards for Teachers of English Language and Literacy in Australia) project. (RS)

Political Animals: The Paradox of Ecofeminist Politics.

ERIC Educational Resources Information Center

Sandilands, Catriona

1994-01-01

Analyzes the paradox between the careful work of rigorous political analysis and philosophy and a desire for mystery and the experience of awe and wildness that demands putting aside careful reasoning and the sensing of nature in an altogether different way. (LZ)

What Exactly is the Information Paradox?

NASA Astrophysics Data System (ADS)

Mathur, S. D.

The black hole information paradox tells us something important about the way quantum mechanics and gravity fit together. In these lectures I try to give a pedagogical review of the essential physics leading to the paradox, using mostly pictures. Hawking's argument is recast as a "theorem": if quantum gravity effects are confined to within a given length scale and the vacuum is assumed to be unique, then there will be information loss. We conclude with a brief summary of how quantum effects in string theory violate the first condition and make the interior of the hole a "fuzzball".

The Black Hole Information Paradox and the Collapse of the Wave Function

NASA Astrophysics Data System (ADS)

Okon, Elias; Sudarsky, Daniel

2015-04-01

The black hole information paradox arises from an apparent conflict between the Hawking black hole radiation and the fact that time evolution in quantum mechanics is unitary. The trouble is that while the former suggests that information of a system falling into a black hole disappears, the latter implies that information must be conserved. In this work we discuss the current divergence in views regarding the paradox, we evaluate the role that objective collapse theories could play in its resolution and we propose a link between spontaneous collapse events and microscopic virtual black holes.

The calcium paradox - What should we have to fear?

PubMed Central

de Oliveira, Marcos Aurélio Barboza; Brandi, Antônio Carlos; dos Santos, Carlos Alberto; Botelho, Paulo Henrique Husseni; Cortez, José Luís Lasso; Goissis, Gilberto; Braile, Domingo Marcolino

2014-01-01

The calcium paradox was first mentioned in 1966 by Zimmerman et al. Thereafter gained great interest from the scientific community due to the fact of the absence of calcium ions in heart muscle cells produce damage similar to ischemia-reperfusion. Although not all known mechanisms involved in cellular injury in the calcium paradox intercellular connection maintained only by nexus seems to have a key role in cellular fragmentation. The addition of small concentrations of calcium, calcium channel blockers, and hyponatraemia hypothermia are important to prevent any cellular damage during reperfusion solutions with physiological concentration of calcium. PMID:25140476

Trends in added sugar supply and consumption in Australia: there is an Australian Paradox

PubMed Central

2013-01-01

In 2011, Barclay and Brand-Miller reported the observation that trends in refined sugar consumption in Australia were the inverse of trends in overweight and obesity (The Australian Paradox). Rikkers et al. claim that the Australian Paradox is based on incomplete data because the sources utilised did not incorporate estimates for imported processed foods. This assertion is incorrect. Indeed, national nutrition surveys, sugar consumption data from the United Nations Food and Agricultural Organisation, the Australian Bureau of Statistics and Australian beverage industry data all incorporated data on imported products. PMID:24079329

Reinterpretation of Halokinetic Features in the Ancestral Rocky Mountains Paradox Salt Basin, Utah and Colorado

NASA Astrophysics Data System (ADS)

Thompson, J. A.; Giles, K. A.; Rowan, M. G.; Hearon, T. E., IV

2016-12-01

The Paradox Basin in southeastern Utah and southwestern Colorado is a foreland basin formed in response to flexural loading by the Pennsylvanian-aged Uncompaghre uplift during the Ancestral Rocky Mountain orogen. Thick sequences of evaporites (Paradox Formation) were deposited within the foreland basin, which interfinger with clastic sediments in the foredeep and carbonates around the basin margin. Differential loading of the Pennsylvanian-Jurassic sediments onto the evaporites drove synsedimentary halokinesis, creating a series of salt walls and adjacent minibasins within the larger foreland basin. The growing salt walls within the basin influenced patterns of sediment deposition from the Pennsylvanian through the Cretaceous. By integrating previously published mapping with recent field observations, mapping, and subsurface interpretations of well logs and 2D seismic lines, we present interpretations of the timing, geometry, and nature of halokinesis within the Paradox Basin, which record the complex salt tectonic history in the basin. Furthermore, we present recent work on the relationships between the local passive salt history and the formation of syndepositional counter-regional extensional fault systems within the foreland. These results will be integrated into a new regional salt-tectonic and stratigraphic framework of the Paradox Basin, and have broader implications for interpreting sedimentary records in other basins with a mobile substrate.

Geologic appraisal of Paradox basin salt deposits for water emplacement

USGS Publications Warehouse

Hite, Robert J.; Lohman, Stanley William

1973-01-01

Thick salt deposits of Middle Pennsylvanian age are present in an area of 12,000 square miles in the Paradox basin of southeast Utah and southwest Colorado. The deposits are in the Paradox Member of the Hermosa Formation. The greatest thickness of this evaporite sequence is in a troughlike depression adjacent to the Uncompahgre uplift on the northeast side of the basin.The salt deposits consist of a cyclical sequence of thick halite units separated by thin units of black shale, dolomite, and anhydrite. Many halite units are several hundred feet thick and locally contain economically valuable potash deposits.Over much of the Paradox basin the salt deposits occur at depths of more than 5,000 feet. Only in a series of salt anticlines located along the northeastern side of the basin do the salt deposits rise to relatively shallow depths. The salt anticlines can be divided geographically and structurally into five major systems. Each system consists of a long undulating welt of thickened salt over which younger rocks are arched in anticlinal form. Locally there are areas along the axes of the anticlines where the Paradox Member was never covered by younger sediments. This allowed large-scale migration of Paradox strata toward and up through these holes in the sediment cover forming diapiric anticlines.The central or salt-bearing cores of the anticlines range in thickness from about 2,500 to 14,000 feet. Structure in the central core of the salt anticlines is the result of both regional-compression and flowage of the Paradox Member into the anticlines from adjacent synclines. Structure in the central cores of the salt anticlines ranges from relatively undeformed beds to complexly folded and faulted masses, in which stratigraphic continuity is undemonstrable.The presence of thick cap rock .over many of the salt anticlines is evidence of removal of large volumes of halite by groundwater. Available geologic and hydrologic information suggests that this is a relatively slow process and that any waste-storage or disposal sites in these structures should remain dry for hundreds of thousands of years.Trace to commercial quantities of oil and gas are found in all of the black shale-dolomite-anhydrite interbeds of the Paradox Member. These hydrocarbons constitute a definite hazard in the construction and operation of underground waste-storage or disposal facilities. However, many individual halite beds are of. sufficient thickness that a protective seal of halite can be left between the openings and the gassy beds.A total of 12 different localities were considered to be potential waste-storage or disposal sites in the Paradox basin. Two Sharer dome and Salt Valley anticline, were considered to have the most favorable characteristics.

Unequal Schools, Unequal Chances: The Challenges to Equal Opportunity in the Americas. The David Rockefeller Center Series on Latin American Studies.

ERIC Educational Resources Information Center

Reimers, Fernando, Ed.

This book aims to unveil some of the intricacies and paradoxes in the links among education, poverty, and inequality in the Americas by offering a current account of the status of educational opportunities for low-income groups. The goal is to offer various frameworks to conceptualize the dynamics of educational inequality at the micro-level and…

Less is more: Patient-level meta-analysis reveals paradoxical dose-response effects of a computer-based social anxiety intervention targeting attentional bias.

PubMed

Price, Rebecca B; Kuckertz, Jennie M; Amir, Nader; Bar-Haim, Yair; Carlbring, Per; Wallace, Meredith L

2017-12-01

The past decade of research has seen considerable interest in computer-based approaches designed to directly target cognitive mechanisms of anxiety, such as attention bias modification (ABM). By pooling patient-level datasets from randomized controlled trials of ABM that utilized a dot-probe training procedure, we assessed the impact of training "dose" on relevant outcomes among a pooled sample of 693 socially anxious adults. A paradoxical effect of the number of training trials administered was observed for both posttraining social anxiety symptoms and behavioral attentional bias (AB) toward threat (the target mechanism of ABM). Studies administering a large (>1,280) number of training trials showed no benefit of ABM over control conditions, while those administering fewer training trials showed significant benefit for ABM in reducing social anxiety (P = .02). These moderating effects of dose were not better explained by other examined variables and previously identified moderators, including patient age, training setting (laboratory vs. home), or type of anxiety assessment (clinician vs. self-report). Findings inform the optimal dosing for future dot-probe style ABM applications in both research and clinical settings, and suggest several novel avenues for further research. © 2017 Wiley Periodicals, Inc.

Exploring nursing students’ experience of peer learning in clinical practice

PubMed Central

Ravanipour, Maryam; Bahreini, Masoud; Ravanipour, Masoumeh

2015-01-01

Background: Peer learning is an educational process wherein someone of the same age or level of experience level interacts with other students interested in the same topic. There is limited evidence specifically focusing on the practical use of peer learning in Iran. The aim of this study was to explore nursing students’ experiences of peer learning in clinical practice. Materials and Methods: A qualitative content analysis was conducted. Focus groups were used to find the students’ experiences about peerlearning. Twenty-eight baccalaureate nursing students at Bushehr University of Medical Sciences were selected purposively, and were arranged in four groups of seven students each. The focus group interviews were conducted using a semi-structured interview schedule. All interviews were tape-recorded, transcribed verbatim, and analyzed using conventional content analysis method. Results: The analysis identified four themes: Paradoxical dualism, peer exploitation, first learning efficacy, and socialization practice. Gained advantages and perceived disadvantages created paradoxical dualism, and peer exploitation resulted from peer selection and peer training. Conclusion: Nursing students reported general satisfaction concerning peer learning due to much more in-depth learning with little stress than conventional learning methods. Peer learning is a useful method for nursing students for practicing educational leadership and learning the clinical skills before they get a job. PMID:26097860

Sleep in prenatally restraint stressed rats, a model of mixed anxiety-depressive disorder.

PubMed

Mairesse, Jérôme; Van Camp, Gilles; Gatta, Eleonora; Marrocco, Jordan; Reynaert, Marie-Line; Consolazione, Michol; Morley-Fletcher, Sara; Nicoletti, Ferdinando; Maccari, Stefania

2015-01-01

Prenatal restraint stress (PRS) can induce persisting changes in individual's development. PRS increases anxiety and depression-like behaviors and induces changes in the hypothalamo-pituitary-adrenal (HPA) axis in adult PRS rats after exposure to stress. Since adaptive capabilities also depend on temporal organization and synchronization with the external environment, we studied the effects of PRS on circadian rhythms, including the sleep-wake cycle, that are parameters altered in depression. Using a restraint stress during gestation, we showed that PRS induced phase advances in hormonal/behavioral circadian rhythms in adult rats, and an increase in the amount of paradoxical sleep, positively correlated to plasma corticosterone levels. Plasma corticosterone levels were also correlated with immobility in the forced swimming test, indicating a depressive-like profile in the PRS rats. We observed comorbidity with anxiety-like profile on PRS rats that was correlated with a reduced release of glutamate in the ventral hippocampus. Pharmacological approaches aimed at modulating glutamate release may represent a novel therapeutic strategy to treat stress-related disorders. Finally, since depressed patients exhibit changes in HPA axis activity and in circadian rhythmicity as well as in the paradoxical sleep regulation, we suggest that PRS could represent an original animal model of depression.

Erythropoietin binding protein from mammalian serum

DOEpatents

Clemons, Gisela K.

1997-01-01

Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described.

Erythropoietin binding protein from mammalian serum

DOEpatents

Clemons, G.K.

1997-04-29

Purified mammalian erythropoietin binding-protein is disclosed, and its isolation, identification, characterization, purification, and immunoassay are described. The erythropoietin binding protein can be used for regulation of erythropoiesis by regulating levels and half-life of erythropoietin. A diagnostic kit for determination of level of erythropoietin binding protein is also described. 11 figs.

Relative Propensities of Cytochrome c Oxidase and Cobalt Corrins for Reaction with Cyanide and Oxygen: Implications for Amelioration of Cyanide Toxicity.

PubMed

Yuan, Quan; Pearce, Linda L; Peterson, Jim

2017-12-18

In aqueous media at neutral pH, the binding of two cyanide molecules per cobinamide can be described by two formation constants, K f1 = 1.1 (±0.6) × 10 5 M -1 and K f2 = 8.5 (±0.1) × 10 4 M -1 , or an overall cyanide binding constant of ∼1 × 10 10 M -2 . In comparison, the cyanide binding constants for cobalamin and a fully oxidized form of cytochrome c oxidase, each binding a single cyanide anion, were found to be 7.9 (±0.5) × 10 4 M -1 and 1.6 (±0.2) × 10 7 M -1 , respectively. An examination of the cyanide-binding properties of cobinamide at neutral pH by stopped-flow spectrophotometry revealed two kinetic phases, rapid and slow, with apparent second-order rate constants of 3.2 (±0.5) × 10 3 M -1 s -1 and 45 (±1) M -1 s -1 , respectively. Under the same conditions, cobalamin exhibited a single slow cyanide-binding kinetic phase with a second-order rate constant of 35 (±1) M -1 s -1 . All three of these processes are significantly slower than the rate at which cyanide is bound by complex IV during enzyme turnover (>10 6 M -1 s -1 ). Overall, it can be understood from these findings why cobinamide is a measurably better cyanide scavenger than cobalamin, but it is unclear how either cobalt corrin can be antidotal toward cyanide intoxication as neither compound, by itself, appears able to out-compete cytochrome c oxidase for available cyanide. Furthermore, it has also been possible to unequivocally show in head-to-head comparison assays that the enzyme does indeed have greater affinity for cyanide than both cobalamin and cobinamide. A plausible resolution of the paradox that both cobalamin and cobinamide clearly are antidotal toward cyanide intoxication, involving the endogenous auxiliary agent nitric oxide, is suggested. Additionally, the catalytic consumption of oxygen by the cobalt corrins is demonstrated and, in the case of cobinamide, the involvement of cytochrome c when present. Particularly in the case of cobinamide, these oxygen-dependent reactions could potentially lead to erroneous assessment of the ability of the cyanide scavenger to restore the activity of cyanide-inhibited cytochrome c oxidase.

The lactate paradox revisited in lowlanders during acclimatization to 4100 m and in high-altitude natives

PubMed Central

van Hall, G; Lundby, C; Araoz, M; Calbet, J A L; Sander, M; Saltin, B

2009-01-01

Chronic hypoxia has been proposed to induce a closer coupling in human skeletal muscle between ATP utilization and production in both lowlanders (LN) acclimatizing to high altitude and high-altitude natives (HAN), linked with an improved match between pyruvate availability and its use in mitochondrial respiration. This should result in less lactate being formed during exercise in spite of the hypoxaemia. To test this hypothesis six LN (22–31 years old) were studied during 15 min warm up followed by an incremental bicycle exercise to exhaustion at sea level, during acute hypoxia and after 2 and 8 weeks at 4100 m above sea level (El Alto, Bolivia). In addition, eight HAN (26–37 years old) were studied with a similar exercise protocol at altitude. The leg net lactate release, and the arterial and muscle lactate concentrations were elevated during the exercise in LN in acute hypoxia and remained at this higher level during the acclimatization period. HAN had similar high values; however, at the moment of exhaustion their muscle lactate, ADP and IMP content and Cr/PCr ratio were higher than in LN. In conclusion, sea-level residents in the course of acclimatization to high altitude did not exhibit a reduced capacity for the active muscle to produce lactate. Thus, the lactate paradox concept could not be demonstrated. High-altitude natives from the Andes actually exhibit a higher anaerobic energy production than lowlanders after 8 weeks of acclimatization reflected by an increased muscle lactate accumulation and enhanced adenine nucleotide breakdown. PMID:19139048

Interpreting irregularity in small-scale, cyclical precipitation of halite-anhydrite couplets within the Pennsylvanian Paradox Formation, Paradox Basin, Utah

NASA Astrophysics Data System (ADS)

Marra, K. R.; Agena, W. F.; Dubiel, R. F.; Lee, M. W.; Pitman, J. K.

2012-12-01

The Pennsylvanian Paradox Formation (Hermosa Group) contains 33 documented evaporite cycles consisting of thick (6-240 m) halite successions interbedded with anhydrite, silty dolomite, and black shale. The evaporite deposits precipitated from marine brines under restricted circulation conditions in the Paradox Basin, a northwest-southeast trending asymmetrical trough formed adjacent to the Uncompahgre uplift, where periodic glacioeustatic sea-level fluctuations and intermittent meteoric water influxes altered salinity gradients. Each salt cycle contains rhythmically bedded halite-anhydrite couplets, in which anhedral to euhedral bottom-growth halite crystals are overlain by thin (mm-scale), subaqueously precipitated layers of anhydrite in the form of "snow-on-the-roof" texture. Discrete grains of sylvite, which are red due to hematite inclusions, locally occur as bands or aggregates throughout most salt packages. In order to delineate controls on high-frequency halite-anhydrite precipitation, the thickness of distinct couplets were measured in four salt cycles, two (Cycles 3 and 5) in the Cane Creek No.1 corehole and two (Cycles 5 and 13) in the Shafer No. 1 corehole. The cores were drilled approximately 8 km apart within the central portion of the basin near the crests of the Cane Creek and Shafer salt anticlines. The thickness of halite-anhydrite couplets ranges between 1-90 cm for all measured cycles, with the most commonly occurring thickness of approximately 3-4 cm. Despite the proximity of the two cores, the salt cycles in the Shafer No. 1 core are 12-15m thicker than in the Cane Creek No. 1 core, and individual couplets thicken within the middle (~20 m) of the salt section. In contrast, couplets thicken near the top of the halite bed in the Cane Creek No.1 core, which is most pronounced in Cycle 5. Locally disrupted and distorted laminae due to salt flowage, however, complicates some laminae measurements. The small-scale, cyclical pattern of halite-anhydrite couplets within the Paradox Formation may have resulted from annual water temperature (and corresponding calcium sulfate solubility) fluctuations or irregular influxes of meteoric waters due to storm or monsoon events. Interannual disturbances due to Spring and neap tides may have also played a role. The presence of sylvite may reflect a climatic overprint of arid conditions, which promoted eolian iron dispersal. Spectral analyses are being conducted on all measured salt cycles to discern bunching patterns in halite-anhydrite couplet thicknesses.

Level of Awareness and Knowledge of Breast Cancer in Nigeria. A Systematic Review.

PubMed

Olayide, Agodirin S; Halimat, Akande J; Samuel, Olatoke A; Ganiyu, Rahman A; Soliu, Oguntola A

2017-03-01

Despite reports of improved awareness of breast cancer entity and seemingly upbeat levels of other awareness subthemes in Nigeria, patients continue to present late when treatment is least rewarding. This paradoxical trend of both rising awareness and late presentation coupled with reports suggesting other competing drivers of late presentation question the "theory of poor awareness" as the foremost driver of late presentations. By aggregating available data, we aimed to assess what still constitutes poor breast cancer awareness in Nigeria in order to suggest how to allocate resources to reverse the paradox. Studies conducted on Nigerian populace from 2000 to date were reviewed systematically. Search was made in PROSPERO, PubMed/MEDLINE, AJOL, Cochrane library, GOOGLE, ResearchGate and ACADEMIA. Primary outcome was level of awareness about breast cancer entity. Fifty-one eligible (48 descriptive surveys, 3 interventional ones) studies were reviewed. They included 19,598 respondents (98.5% females; 43% rural dwellers). 17,086(87.2%) were laypersons in various walks of life; 2,512(12.8%) were healthcare professionals. There were high levels of awareness of breast cancer entity, BSE, knowledge of fatality and benefit of early detection (weighted percentages 80.6%, 60.1%, 73.2% and 73.9% respectively). Weighted percentages of knowledge of symptoms/signs was 45.1%. Weighted percentages of sense of susceptibility and performance of BSE were low-26.8% and 22.9% respectively. Generally, rate of performance of screening did not vary with changes in the level of awareness/knowledge of concepts. In general, low awareness of breast cancer may not be the direct and foremost driver of persistent late presentation in Nigeria.

THE PARADOX OF THE PLANKTON: COMMUNITY STRUCTURE PROMOTES BLOOMS

EPA Science Inventory

ABSTRACT: The 'paradox of the plankton' refers to commensalism as well as symbiosis, predation, and impacts of non equilibrium conditions between two planktonic

competitors. In regards to commensalism, phytoplankton can release organic carbon that enhances growth of its ba...

Review Essay: Pondering Pedagogical Paradoxes

ERIC Educational Resources Information Center

Spencer, Leland G.

2015-01-01

Herein, Leland Spencer provides a review of four book selections while reflecting on paradoxes regularly faced by feminist teachers (and scholars, activists, and thinkers). The books include: (1) Bradley, Harriet. "Gender." Cambridge: Polity, 2012. Print; (2) Murphy, Michael J., and Elizabeth N. Ribarsky, eds. "Activities for…

Allosteric Transmission along a Loosely Structured Backbone Allows a Cardiac Troponin C Mutant to Function with Only One Ca2+ Ion*

PubMed Central

Marques, Mayra de A.; Pinto, Jose Renato; Moraes, Adolfo H.; Iqbal, Anwar; de Magalhães, Mariana T. Q.; Monteiro, Jamila; Pedrote, Murilo M.; Sorenson, Martha M.; de Oliveira, Guilherme A. P.

2017-01-01

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiomyopathies and a major cause of sudden death in young athletes. The Ca2+ sensor of the sarcomere, cardiac troponin C (cTnC), plays an important role in regulating muscle contraction. Although several cardiomyopathy-causing mutations have been identified in cTnC, the limited information about their structural defects has been mapped to the HCM phenotype. Here, we used high-resolution electron-spray ionization mass spectrometry (ESI-MS), Carr-Purcell-Meiboom-Gill relaxation dispersion (CPMG-RD), and affinity measurements of cTnC for the thin filament in reconstituted papillary muscles to provide evidence of an allosteric mechanism in mutant cTnC that may play a role to the HCM phenotype. We showed that the D145E mutation leads to altered dynamics on a μs-ms time scale and deactivates both of the divalent cation-binding sites of the cTnC C-domain. CPMG-RD captured a low populated protein-folding conformation triggered by the Glu-145 replacement of Asp. Paradoxically, although D145E C-domain was unable to bind Ca2+, these changes along its backbone allowed it to attach more firmly to thin filaments than the wild-type isoform, providing evidence for an allosteric response of the Ca2+-binding site II in the N-domain. Our findings explain how the effects of an HCM mutation in the C-domain reflect up into the N-domain to cause an increase of Ca2+ affinity in site II, thus opening up new insights into the HCM phenotype. PMID:28049727

Role of the Local Anesthetic Receptor in the State-Dependent Inhibition of Voltage-Gated Sodium Channels by the Insecticide Metaflumizone

PubMed Central

von Stein, Richard T.

2012-01-01

Sodium channel inhibitor (SCI) insecticides selectively target voltage-gated sodium (Nav) channels in the slow-inactivated state by binding at or near the local anesthetic receptor within the sodium channel pore. Metaflumizone is a new insecticide for the treatment of fleas on domesticated pets and has recently been reported to block insect sodium channels in the slow-inactivated state, thereby implying that it is also a member of the SCI class. Using the two-electrode voltage-clamp technique, we examined metaflumizone inhibition of rat Nav1.4 sodium channels expressed in Xenopus laevis oocytes. Metaflumizone selectively inhibited Nav1.4 channels at potentials that promoted slow inactivation and shifted the voltage dependence of slow inactivation in the direction of hyperpolarization. Metaflumizone perfusion at a hyperpolarized holding potential also shifted the conductance-voltage curve for activation in the direction of depolarization and antagonized use-dependent lidocaine inhibition of fast-inactivated sodium channels, actions not previously observed with other SCI insecticides. We expressed mutated Nav1.4/F1579A and Nav1.4/Y1586A channels to investigate whether metaflumizone shares the domain IV segment S6 (DIV-S6) binding determinants identified for other SCI insecticides. Consistent with previous investigations of SCI insecticides on rat Nav1.4 channels, the F1579A mutation reduced sensitivity to block by metaflumizone, whereas the Y1586A mutation paradoxically increased the sensitivity to metaflumizone. We conclude that metaflumizone selectively inhibits slow-inactivated Nav1.4 channels and shares DIV-S6 binding determinants with other SCI insecticides and therapeutic drugs. However, our results suggest that metaflumizone interacts with resting and fast-inactivated channels in a manner that is distinct from other compounds in this insecticide class. PMID:22127519

Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli

PubMed Central

Greene, Sarah E.; Hibbing, Michael E.; Janetka, James; Chen, Swaine L.

2015-01-01

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the primary cause of community-acquired urinary tract infections (UTIs). UPEC bind the bladder using type 1 pili, encoded by the fim operon in nearly all E. coli. Assembled type 1 pili terminate in the FimH adhesin, which specifically binds to mannosylated glycoproteins on the bladder epithelium. Expression of type 1 pili is regulated in part by phase-variable inversion of the genomic element containing the fimS promoter, resulting in phase ON (expressing) and OFF (nonexpressing) orientations. Type 1 pili are essential for virulence in murine models of UTI; however, studies of urine samples from human UTI patients demonstrate variable expression of type 1 pili. We provide insight into this paradox by showing that human urine specifically inhibits both expression and function of type 1 pili. Growth in urine induces the fimS phase OFF orientation, preventing fim expression. Urine also contains inhibitors of FimH function, and this inhibition leads to a further bias in fimS orientation toward the phase OFF state. The dual effect of urine on fimS regulation and FimH binding presents a potential barrier to type 1 pilus-mediated colonization and invasion of the bladder epithelium. However, FimH-mediated attachment to human bladder cells during growth in urine reverses these effects such that fim expression remains ON and/or turns ON. Interestingly, FimH inhibitors called mannosides also induce the fimS phase OFF orientation. Thus, the transduction of FimH protein attachment or inhibition into epigenetic regulation of type 1 pilus expression has important implications for the development of therapeutics targeting FimH function. PMID:26126855

Promotor(a)s, the organizations in which they work, and an emerging paradox: how organizational structure and scope impact promotor(a)s' work.

PubMed

May, Marlynn L; Contreras, Ricardo B

2007-07-01

To analyze how organizational structures and scope (geographic and programmatic) generate dissonance between the organization and its workers, creating a paradox with policy implications for access to health care in hard-to-reach populations. The workers are lay community health workers called promotor(a)s. The organizations are community based organizations in which the promotor(a)s work, either as volunteers, part-time or as full-time wage staff. Ethnographic study of 12 organizations and their promotor(a)s. Data gathering included interviews with organization directors, promotor(a)s, service providers working with the organizations, and community residents served by the organizations and workers. In addition, promotor(a)s were observed in the course of their work. Sampling was a non-probability, snowball procedure for identifying the organizations and the workers within them. A paradox is emerging between (a) promotor(a)s who perceive their work to be locally focused and tightly integrated with the communities they serve and live in, and (b) the employing organizations that are expanding in geographical and programmatic scope because the work promotor(a)s do is in increasing demand by agencies and funding sources external to the communities served. The paradox potentially threatens to undermine and transform the work and working environment of the promotor(a)s. The challenge is to find a balance that will sustain a workable and working relationship among the organization, the workers, and the communities served. Care is needed in setting out policies that translate the paradox into greater congruence among organization, workers and communities. Policy needs discussed focus on (a) worker training, (b) worker employment and deployment, and (c) funding source recognition of the paradox.

Paradoxical sphincter contraction is rarely indicative of anismus

PubMed Central

Voderholzer, W; Neuhaus, D; Klauser, A; Tzavella, K; Muller-Lissner, S; Schindlbeck, N

1997-01-01

Background—Anismus is thought to be a cause of chronic constipation by producing outlet obstruction. The underlying mechanism is paradoxical contraction of the anal sphincter or puborectalis muscle. However, paradoxical sphincter contraction (PSC) also occurs in healthy controls, so anismus may be diagnosed too often because it may be based on a non-specific finding related to untoward conditions during the anorectal examination. 
Aims—To investigate the pathophysiological importance of PSC found at anorectal manometry in constipated patients and in patients with stool incontinence. 
Methods—Digital rectal examination and anorectal manometry were performed in 102 chronically constipated patients, 102 patients with stool incontinence, and in 18 controls without anorectal disease. In 120 of the 222 subjects defaecography was also performed. Paradoxical sphincter contraction was defined as a sustained increase in sphincter pressure during straining. Anismus was assumed when PSC was present on anorectal manometry and digital rectal examination and the anorectal angle did not widen on defaecography. 
Results—Manometric PSC occurred about twice as often in constipated patients as in incontinent patients (41.2% versus 25.5%, p<0.017) and its prevalence was similar in incontinent patients and controls (25.5% versus 22.2%). Oroanal or rectosigmoid transit times in constipated patients with and without PSC did not differ significantly (total 64.6 (8.9) hours versus 54.2 (8.1) hours; rectosigmoid 14.9 (2.4) hours versus 13.8 (2.5) hours). 
Conclusions—Paradoxical sphincter contraction is a common finding in healthy controls as well as in patients with chronic constipation and stool incontinence. Hence, PSC is primarily a laboratory artefact and true anismus is rare. 

 Keywords: anismus; paradoxical sphincter contraction; constipation; stool incontinence; anorectal manometry PMID:9301508

An experimental study of the Online Information Paradox: Does en-route information improve road network performance?

PubMed Central

2017-01-01

This study investigates the empirical presence of a theoretical transportation paradox, defined as the “Online Information Paradox” (OIP). The paradox suggests that, for certain road networks, the provision of online information deteriorate travel conditions for all users of that network relative to the situation where no online information is provided to users. The analytical presence of the paradox was derived for a specific network structure by using two equilibrium models, the first being the Expected User Equilibrium (EUE) solution (no information scenario) and the other being the User Equilibrium with Recourse (UER) solution (with information scenario). An incentivised computerised route choice game was designed using the concepts of experimental economics and administered in a controlled laboratory environment to investigate the physical presence of the paradox. Aggregate statistics of path flows and Total System Travel Costs (TSTC) were used to compare the experimental results with the theoretical findings. A total of 12 groups of 12 participants completed the experiment and the OIP and the occurrence of the OIP being significant was observed in 11 of the 12 cases. Though information increased travel costs for users on average, it reduced the volatility of travel costs experienced in the no information scenario indicating that information can achieve a more reliable system. Further replications of similar experiments and more importantly field based identification of the phenomena will force transport professionals to be aware of the emergence of the paradox. In addition, studies such as this emphasise the need for the adoption of adaptive traffic assignment techniques to appropriately model the acquisition of information on a road network. PMID:28902854

Unintended consequence of managing the coupled humans and water: the irrigation efficiency paradox

NASA Astrophysics Data System (ADS)

Liu, Y.

2015-12-01

Water shortage most severely restricts the socio-economic development of many arid and semi-arid regions in the world, for which water-saving technology is believed to be an effective solution. However, as a realworld case, the total water consumption of Xinjiang Uygur Autonomous Region of China continued to increase as irrigation efficiency dramatically improved through the application of water-saving technology in the study period 1998-2010. This phenomenon, known as the irrigation efficiency paradox or Jevons paradox, is interpreted as an economic rebound effect. In this study, we explore the dynamic feedbacks between humans and water in this paradox through a socio-hydrological perspective. We analyze the co-evolutionary trajectory of coupled human-water dynamics from 1950 to 2010 to provide it a general context. A conceptual socio-hydrological model based on five key elements, namely, irrigation land, water-saving technology, water consumption, societal sensitivity to water scarcity, and the policy mix, is constructed. The policy mix to be adopted is determined by a social decision-making process mainly based on the societal sensitivity, which reflects the societal preference on two sorts of policies: (i) irrigation land control and (ii) water-saving technology promotion. Modeling results verify the hypothesized mechanism by successfully reproducing the observed dynamics including the emergence of the efficiency paradox. Our analysis indicates that the implementation of more adaptive rules may even eliminate the paradox. The effects of different initial policy mixes are also explored, and the results show that land control policies should be given equal priority when dealing with water scarcity. These findings point to a double-helix-type co-evolution of humans and water.

Structural styles of the paradox basin: Something to consider in a basin dominated by stratigraphic traps

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevenson, G.M.

1993-08-01

The Paradox basin has produced a considerable amount of oil and gas from Pennsylvanian and Mississippian reservoirs. Most of the production has been from stratigraphic traps associated with subtle rejuvenated basement structures. Only the Blanding sub-basin and west flank of the salt anticlines (Lisbon Valley to Salt Wash fields) have been explored in sufficient quantity to classify as the mature parts of the basin, and even in these areas, new fields are currently being discovered. The majority of the basin still remains an exploration frontier. Certainly, structural and stratigraphic conditions analogous to those in the proven areas exist in muchmore » of these underexplored parts of the Paradox basin, but the potential for new and different types of hydrocarbon traps should not be overlooked. Structural styles present in the Paradox basin range from high-angle reverse, to normal, to inverted, which records different periods of crustal shortening and extension. To provide a full appreciation of the variety and complexities of structural styles in the Paradox basin and their influence on the orientation and distribution of different stratigraphic mechanisms, comparisons are made in the following areas: the Uncompahgre frontal fault zone, salt anticlines, Cane Creek anticline, Nequoia arch, Blanding basin, and Hogback monocline. To demonstrate the episodic nature of tectonism throughout the entire Phanerozoic Era, potential and proven hydrocarbon trapping styles are illustrated in strata ranging from Devonian to Late Pennsylvanian age. In particular, the Pennsylvanian Paradox evaporites and equivalent shelf carbonates and siliciclastics provide an excellent example of chronostratigraphic and glacioeustatic relationships. Due to the proven prolific nature of these Pennsylvanian reservoirs, the interrelationships of structure to stratigraphy in the Blanding basin and along the Cane Creek anticline will be emphasized.« less

PTB and TIAR binding to insulin mRNA 3'- and 5'UTRs; implications for insulin biosynthesis and messenger stability.

PubMed

Fred, Rikard G; Mehrabi, Syrina; Adams, Christopher M; Welsh, Nils

2016-09-01

Insulin expression is highly controlled on the posttranscriptional level. The RNA binding proteins (RBPs) responsible for this result are still largely unknown. To identify RBPs that bind to insulin mRNA we performed mass spectrometry analysis on proteins that bound synthetic oligonucloetides mimicing the 5'- and the 3'-untranslated regions (UTRs) of rat and human insulin mRNA in vitro . We observed that the RBPs heterogeneous nuclear ribonucleoprotein (hnRNP) U, polypyrimidine tract binding protein (PTB), hnRNP L and T-cell restricted intracellular antigen 1-related protein (TIA-1-related protein; TIAR) bind to insulin mRNA sequences, and that the in vitro binding affinity of these RBPs changed when INS-1 cells were exposed to glucose, 3-isobutyl-1-methylxanthine (IBMX) or nitric oxide. High glucose exposure resulted in a modest increase in PTB and TIAR binding to an insulin mRNA sequence. The inducer of nitrosative stress DETAnonoate increased markedly hnRNP U and TIAR mRNA binding. An increased PTB to TIAR binding ratio in vitro correlated with higher insulin mRNA levels and insulin biosynthesis rates in INS-1 cells. To further investigate the importance of RNA-binding proteins for insulin mRNA stability, we decreased INS-1 and EndoC-βH1 cell levels of PTB and TIAR by RNAi. In both cell lines, decreased levels of PTB resulted in lowered insulin mRNA levels while decreased levels of TIAR resulted in increased insulin mRNA levels. Thapsigargin-induced stress granule formation was associated with a redistribution of TIAR from the cytosol to stress granules. These experiments indicate that alterations in insulin mRNA stability and translation correlate with differential RBP binding. We propose that the balance between PTB on one hand and TIAR on the other participates in the control of insulin mRNA stability and utilization for insulin biosynthesis.

CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis.

PubMed

Zitouni, Sihem; Francia, Maria E; Leal, Filipe; Montenegro Gouveia, Susana; Nabais, Catarina; Duarte, Paulo; Gilberto, Samuel; Brito, Daniela; Moyer, Tyler; Kandels-Lewis, Steffi; Ohta, Midori; Kitagawa, Daiju; Holland, Andrew J; Karsenti, Eric; Lorca, Thierry; Lince-Faria, Mariana; Bettencourt-Dias, Mónica

2016-05-09

Centrioles are essential for the assembly of both centrosomes and cilia. Centriole biogenesis occurs once and only once per cell cycle and is temporally coordinated with cell-cycle progression, ensuring the formation of the right number of centrioles at the right time. The formation of new daughter centrioles is guided by a pre-existing, mother centriole. The proximity between mother and daughter centrioles was proposed to restrict new centriole formation until they separate beyond a critical distance. Paradoxically, mother and daughter centrioles overcome this distance in early mitosis, at a time when triggers for centriole biogenesis Polo-like kinase 4 (PLK4) and its substrate STIL are abundant. Here we show that in mitosis, the mitotic kinase CDK1-CyclinB binds STIL and prevents formation of the PLK4-STIL complex and STIL phosphorylation by PLK4, thus inhibiting untimely onset of centriole biogenesis. After CDK1-CyclinB inactivation upon mitotic exit, PLK4 can bind and phosphorylate STIL in G1, allowing pro-centriole assembly in the subsequent S phase. Our work shows that complementary mechanisms, such as mother-daughter centriole proximity and CDK1-CyclinB interaction with centriolar components, ensure that centriole biogenesis occurs once and only once per cell cycle, raising parallels to the cell-cycle regulation of DNA replication and centromere formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

The paradox of characteristics of silicon detectors operated at temperature close to liquid helium

NASA Astrophysics Data System (ADS)

Eremin, V.; Shepelev, A.; Verbitskaya, E.; Zamantzas, C.; Galkin, A.

2018-05-01

The aim of this study is to give characterization of silicon p+/n/n+ detectors for the monitoring systems of the Large Hadron Collider machine at CERN with the focus on justifying the choice of silicon resistivity for the detector operation at the temperature of 1.9-10 K. The detectors from n-type silicon with the resistivity of 10, 4.5, and 0.5 kΩ cm were investigated at the temperature from 293 up to 7 K by the Transient Current Technique with a 660 nm pulse laser and alpha-particles. The shapes of the detector current pulse response allowed revealing a paradox in the properties of shallow donors of phosphorus, i.e., native dopants in the n-type Si. There was no carrier freeze-out on the phosphorus energy levels in the space charge region (SCR), and they remained positively charged irrespective of temperature, thus limiting the depleted region depth. As for the base region of a partially depleted detector, the levels became neutral at T < 28 K, which transformed silicon to an insulator. The reduction of the activation energy for carrier emission in the detector SCR estimated in the scope of the Poole-Frenkel effect failed to account for the impact of the electric field on the properties of phosphorus levels. The absence of carrier freeze-out in the SCR justifies the choice of high resistivity silicon as the only proper material for detector operation in a fully depleted mode at extremely low temperature.

Paradoxical psychotherapy in a case of transvestism.

PubMed

Cliffe, M J

1987-09-01

Paradoxical psychotherapy succeeded in removing the compulsive element and reducing the guilt attached to transvestism in a male transvestite patient. Cross-dressing at home became acceptable to him and the temptation to cross-dress in public ended. Data suggested three independent motivational systems in this patient.

The Paradox of Regulations: A Commentary.

ERIC Educational Resources Information Center

Taylor, Steven J.

1992-01-01

This response to previous symposium papers (EC 604 155-161) concerning regulations and quality assurance in Intermediate Care Facilities for the Mentally Retarded (ICF/MR) sees regulations as the bureaucratization of values, identifies paradoxes implicit in regulatory controls, and urges reform of the current developmental disability service…

Art's Pedagogical Paradox

ERIC Educational Resources Information Center

Kalin, Nadine M.

2014-01-01

This article contributes to conversations concerning art education futures through engaging alternative relations between art, education, and democracy that mobilize education as art projects associated with the "pedagogical turn" as sites of liminality and paradox. An analysis of the art project, Pedagogical Factory, is used to outline…

One Iota Fills the Quota: A Paradox in Multifacet Reliability Coefficients.

ERIC Educational Resources Information Center

Conger, Anthony J.

1983-01-01

A paradoxical phenomenon of decreases in reliability as the number of elements averaged over increases is shown to be possible in multifacet reliability procedures (intraclass correlations or generalizability coefficients). Conditions governing this phenomenon are presented along with implications and cautions. (Author)

New paradoxes of risky decision making.

PubMed

Birnbaum, Michael H

2008-04-01

During the last 25 years, prospect theory and its successor, cumulative prospect theory, replaced expected utility as the dominant descriptive theories of risky decision making. Although these models account for the original Allais paradoxes, 11 new paradoxes show where prospect theories lead to self-contradiction or systematic false predictions. The new findings are consistent with and, in several cases, were predicted in advance by simple "configural weight" models in which probability-consequence branches are weighted by a function that depends on branch probability and ranks of consequences on discrete branches. Although they have some similarities to later models called "rank-dependent utility," configural weight models do not satisfy coalescing, the assumption that branches leading to the same consequence can be combined by adding their probabilities. Nor do they satisfy cancellation, the "independence" assumption that branches common to both alternatives can be removed. The transfer of attention exchange model, with parameters estimated from previous data, correctly predicts results with all 11 new paradoxes. Apparently, people do not frame choices as prospects but, instead, as trees with branches.

Evaluation of paradoxical TB–associated IRIS with the use of standardized case definitions for resource limited settings

PubMed Central

Eshun-Wilson, Ingrid; Havers, Fiona; Nachega, Jean B; Prozesky, Hans W; Taljaard, Jantjie J; Zeier, Michele D; Cotton, Mark; Simon, Gary; Soentjens, Patrick

2011-01-01

Objective Standardized case definitions have recently been proposed by the International Network for the Study of HIV-associated IRIS (INSHI) for use in resource-limited settings. We evaluated paradoxical TB-associated IRIS in a large cohort from a TB endemic setting with the use of these case definitions. Design A retrospective cohort analysis. Methods We reviewed records from 1250 South African patients who initiated anti-retroviral therapy (ART) over a five-year period. Results 333 (27%) of the patients in the cohort had prevalent TB at the initiation of ART. Of 54 possible paradoxical TB-associated IRIS cases, 35 fulfilled the INSHI case definitions (11% of TB cases). Conclusions INSHI standardised case definitions were used successfully in identifying paradoxical TB-associated IRIS in this cohort and resulted in a similar proportion of TB IRIS cases (11%) as that reported in previous studies from resource-limited settings (8-13%). This case definition should be evaluated prospectively. PMID:20160249

Quantum information versus black hole physics: deep firewalls from narrow assumptions

NASA Astrophysics Data System (ADS)

Braunstein, Samuel L.; Pirandola, Stefano

2018-07-01

The prevalent view that evaporating black holes should simply be smaller black holes has been challenged by the firewall paradox. In particular, this paradox suggests that something different occurs once a black hole has evaporated to one-half its original surface area. Here, we derive variations of the firewall paradox by tracking the thermodynamic entropy within a black hole across its entire lifetime and extend it even to anti-de Sitter space-times. Our approach sweeps away many unnecessary assumptions, allowing us to demonstrate a paradox exists even after its initial onset (when conventional assumptions render earlier analyses invalid). The most natural resolution may be to accept firewalls as a real phenomenon. Further, the vast entropy accumulated implies a deep firewall that goes `all the way down' in contrast with earlier work describing only a structure at the horizon. This article is part of a discussion meeting issue `Foundations of quantum mechanics and their impact on contemporary society'.

Disability reconsidered: the paradox of physical therapy.

PubMed

Roush, Susan E; Sharby, Nancy

2011-12-01

The purposes of this perspective article are: (1) to explore models of disability from the perspective of the academic discipline of disability studies (DS), (2) to consider the paradox of improving functional capacities while valuing disability as diversity, (3) to identify how physical therapy's use of the International Classification of Functioning, Disability and Health (ICF) disablement model intersects with various disability models, and (4) to apply this broader understanding of disability to physical therapist practice, education, and research. The DS literature has been critical of rehabilitation professionals, particularly targeting the medical model of disability. In contrast, advocates for a social model of disability recognize disability as diversity. It is paradoxical for physical therapy to simultaneously work to ameliorate disability while celebrating it as diversity. The ICF biopsychosocial disablement model offers a mechanism to practice within this paradox and suggests that it is no longer sufficient to conceptualize disability as a purely individual matter that requires attention in isolation from the impact of the larger society.

Black hole firewalls require huge energy of measurement

NASA Astrophysics Data System (ADS)

Hotta, Masahiro; Matsumoto, Jiro; Funo, Ken

2014-06-01

The unitary moving mirror model is one of the best quantum systems for checking the reasoning of the original firewall paradox of Almheiri et al. [J. High Energy Phys. 02 (2013) 062] in quantum black holes. Though the late-time part of radiations emitted from the mirror is fully entangled with the early part, no firewall exists with a deadly, huge average energy flux in this model. This is because the high-energy entanglement structure of the discretized systems in almost maximally entangled states is modified so as to yield the correct description of low-energy effective field theory. Furthermore, the strong subadditivity paradox of firewalls is resolved using nonlocality of general one-particle states and zero-point fluctuation entanglement. Due to the Reeh-Schlieder theorem in quantum field theory, another firewall paradox is inevitably raised with quantum remote measurements in the model. We resolve this paradox from the viewpoint of the energy cost of measurements. No firewall appears, as long as the energy for the measurement is much smaller than the ultraviolet cutoff scale.

Multi-Valued Logic, Neutrosophy, and Schrödinger Equation

NASA Astrophysics Data System (ADS)

Smarandache, Florentin; Christianto, Victor

2017-04-01

Discussing some paradoxes in Quantum Mechanics from the viewpoint of Multi-Valued-logic pioneered by Lukasiewicz, and the recent concept Neutrosophic Logic. Essentially, this new concept offers new insights on the idea of `identity', which too often it has been accepted as given. Neutrosophy itself was developed in attempt to generalize Fuzzy-Logic introduced by L. Zadeh. The discussion is motivated by observation that despite almost eight decades, there is indication that some of those paradoxes known in Quantum Physics are not yet solved. In our knowledge, this is because the solution of those paradoxes requires re-examination of the foundations of logic itself, in particular on the notion of identity and multi-valuedness of entity. The discussion is also intended for young physicist fellows who think that somewhere there should be a `complete' explanation of these paradoxes in Quantum Mechanics. If this it doesn't answer all of their questions, it is our hope that at least it offers a new alternative viewpoint for these old questions.

Effects of behavioral patterns and network topology structures on Parrondo’s paradox

PubMed Central

Ye, Ye; Cheong, Kang Hao; Cen, Yu-wan; Xie, Neng-gang

2016-01-01

A multi-agent Parrondo’s model based on complex networks is used in the current study. For Parrondo’s game A, the individual interaction can be categorized into five types of behavioral patterns: the Matthew effect, harmony, cooperation, poor-competition-rich-cooperation and a random mode. The parameter space of Parrondo’s paradox pertaining to each behavioral pattern, and the gradual change of the parameter space from a two-dimensional lattice to a random network and from a random network to a scale-free network was analyzed. The simulation results suggest that the size of the region of the parameter space that elicits Parrondo’s paradox is positively correlated with the heterogeneity of the degree distribution of the network. For two distinct sets of probability parameters, the microcosmic reasons underlying the occurrence of the paradox under the scale-free network are elaborated. Common interaction mechanisms of the asymmetric structure of game B, behavioral patterns and network topology are also revealed. PMID:27845430

Quantum information versus black hole physics: deep firewalls from narrow assumptions.

PubMed

Braunstein, Samuel L; Pirandola, Stefano

2018-07-13

The prevalent view that evaporating black holes should simply be smaller black holes has been challenged by the firewall paradox. In particular, this paradox suggests that something different occurs once a black hole has evaporated to one-half its original surface area. Here, we derive variations of the firewall paradox by tracking the thermodynamic entropy within a black hole across its entire lifetime and extend it even to anti-de Sitter space-times. Our approach sweeps away many unnecessary assumptions, allowing us to demonstrate a paradox exists even after its initial onset (when conventional assumptions render earlier analyses invalid). The most natural resolution may be to accept firewalls as a real phenomenon. Further, the vast entropy accumulated implies a deep firewall that goes 'all the way down' in contrast with earlier work describing only a structure at the horizon.This article is part of a discussion meeting issue 'Foundations of quantum mechanics and their impact on contemporary society'. © 2018 The Author(s).

Effects of behavioral patterns and network topology structures on Parrondo’s paradox

NASA Astrophysics Data System (ADS)

Ye, Ye; Cheong, Kang Hao; Cen, Yu-Wan; Xie, Neng-Gang

2016-11-01

A multi-agent Parrondo’s model based on complex networks is used in the current study. For Parrondo’s game A, the individual interaction can be categorized into five types of behavioral patterns: the Matthew effect, harmony, cooperation, poor-competition-rich-cooperation and a random mode. The parameter space of Parrondo’s paradox pertaining to each behavioral pattern, and the gradual change of the parameter space from a two-dimensional lattice to a random network and from a random network to a scale-free network was analyzed. The simulation results suggest that the size of the region of the parameter space that elicits Parrondo’s paradox is positively correlated with the heterogeneity of the degree distribution of the network. For two distinct sets of probability parameters, the microcosmic reasons underlying the occurrence of the paradox under the scale-free network are elaborated. Common interaction mechanisms of the asymmetric structure of game B, behavioral patterns and network topology are also revealed.

Transthyretin-binding activity of contaminants in blood from polar bear (Ursus maritimus) cubs.

PubMed

Bytingsvik, Jenny; Simon, Eszter; Leonards, Pim E G; Lamoree, Marja; Lie, Elisabeth; Aars, Jon; Derocher, Andrew E; Wiig, Oystein; Jenssen, Bjørn M; Hamers, Timo

2013-05-07

We determined the transthyretin (TTR)-binding activity of blood-accumulating contaminants in blood plasma samples of approximately 4-months-old polar bear (Ursus maritimus) cubs from Svalbard sampled in 1998 and 2008. The TTR-binding activity was measured as thyroxine (T4)-like equivalents (T4-EQMeas). Our findings show that the TTR-binding activity related to contaminant levels was significantly lower (45%) in 2008 than in 1998 (mean ± standard error of mean: 1998, 2265 ± 231 nM; 2008, 1258 ± 170 nM). Although we cannot exclude a potential influence of between-year differences in capture location and cub body mass, our findings most likely reflect reductions of TTR-binding contaminants or their precursors in the arctic environment (e.g., polychlorinated biphenyls [PCBs]). The measured TTR-binding activity correlated positively with the cubs' plasma levels of hydroxylated PCBs (OH-PCBs). No such association was found between TTR-binding activity and the plasma levels of perfluoroalkyl substances (PFASs). The OH-PCBs explained 60 ± 7% and 54 ± 4% of the TTR-binding activity in 1998 and 2008, respectively, and PFASs explained ≤1.2% both years. Still, almost half the TTR-binding activity could not be explained by the contaminants we examined. The considerable levels of TTR-binding contaminants warrant further effect directed analysis (EDA) to identify the contaminants responsible for the unexplained part of the observed TTR-binding activity.

Liquid-Rich Shale Potential of Utah’s Uinta and Paradox Basins: Reservoir Characterization and Development Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vanden Berg, Michael; Morgan, Craig; Chidsey, Thomas

The enclosed report is the culmination of a multi-year and multi-faceted research project investigating Utah’s unconventional tight oil potential. From the beginning, the project team focused efforts on two different plays: (1) the basal Green River Formation’s (GRF) Uteland Butte unconventional play in the Uinta Basin and (2) the more established but understudied Cane Creek shale play in the Paradox Basin. The 2009-2014 high price of crude oil, coupled with lower natural gas prices, generated renewed interest in exploration and development of liquid hydrocarbon reserves. Following the success of the mid-2000s shale gas boom and employing many of the samemore » well completion techniques, petroleum companies started exploring for liquid petroleum in shale formations. In fact, many shales targeted for natural gas include areas in which the shale is more prone to liquid production. In Utah, organic-rich shales in the Uinta and Paradox Basins have been the source of significant hydrocarbon generation, with companies traditionally targeting the interbedded sands or carbonates for their conventional resource recovery. Because of the advances in horizontal drilling and hydraulic fracturing techniques, operators in these basins started to explore the petroleum production potential of the shale units themselves. The GRF in the Uinta Basin has been studied for over 50 years, since the first hydrocarbon discoveries. However, those studies focused on the many conventional sandstone reservoirs currently producing oil and gas. In contrast, less information was available about the more unconventional crude oil production potential of thinner carbonate/shale units, most notably the basal Uteland Butte member. The Cane Creek shale of the Paradox Basin has been a target for exploration periodically since the 1960s and produces oil from several small fields. The play generated much interest in the early 1990s with the successful use of horizontal drilling. Recently, the USGS assessed the undiscovered oil resource in the Cane Creek shale of the Paradox Basin at 103 million barrels at a 95 percent confidence level and 198 million barrels at a 50 percent confidence level. Nonetheless, limited research was available or published to further define the play and the reservoir characteristics. The specific objectives of the enclosed research were to (1) characterize geologic, geochemical, and geomechanical rock properties of target zones in the two designated basins by compiling data and by analyzing available cores, cuttings, and well logs; (2) describe outcrop reservoir analogs of GRF plays (Cane Creek shale is not exposed) and compare them to subsurface data; (3) map major regional trends for targeted intervals and identify “sweet spots” that have the greatest oil potential; (4) reduce exploration costs and drilling risks, especially in environmentally sensitive areas; (5) improve drilling and fracturing effectiveness by determining optimal well completion design; and (6) reduce field development costs, maximize oil recovery, and increase reserves. These objectives are all addressed in a series of nine publications that resulted from this extensive research project. Each publication is included in this report as an independent appendix.« less

Exploring the isopycnal mixing and helium-heat paradoxes in a suite of Earth system models

NASA Astrophysics Data System (ADS)

Gnanadesikan, A.; Pradal, M.-A.; Abernathey, R.

2015-07-01

This paper uses a suite of Earth system models which simulate the distribution of He isotopes and radiocarbon to examine two paradoxes in Earth science, each of which results from an inconsistency between theoretically motivated global energy balances and direct observations. The helium-heat paradox refers to the fact that helium emissions to the deep ocean are far lower than would be expected given the rate of geothermal heating, since both are thought to be the result of radioactive decay in Earth's interior. The isopycnal mixing paradox comes from the fact that many theoretical parameterizations of the isopycnal mixing coefficient ARedi that link it to baroclinic instability project it to be small (of order a few hundred m2 s-1) in the ocean interior away from boundary currents. However, direct observations using tracers and floats (largely in the upper ocean) suggest that values of this coefficient are an order of magnitude higher. Helium isotopes equilibrate rapidly with the atmosphere and thus exhibit large gradients along isopycnals while radiocarbon equilibrates slowly and thus exhibits smaller gradients along isopycnals. Thus it might be thought that resolving the isopycnal mixing paradox in favor of the higher observational estimates of ARedi might also solve the helium paradox, by increasing the transport of mantle helium to the surface more than it would radiocarbon. In this paper we show that this is not the case. In a suite of models with different spatially constant and spatially varying values of ARedi the distribution of radiocarbon and helium isotopes is sensitive to the value of ARedi. However, away from strong helium sources in the southeastern Pacific, the relationship between the two is not sensitive, indicating that large-scale advection is the limiting process for removing helium and radiocarbon from the deep ocean. The helium isotopes, in turn, suggest a higher value of ARedi below the thermocline than is seen in theoretical parameterizations based on baroclinic growth rates. We argue that a key part of resolving the isopycnal mixing paradox is to abandon the idea that ARedi has a direct relationship to local baroclinic instability and to the so-called "thickness" mixing coefficient AGM.

Renal paradoxical embolism in a hypertensive young adult without acute ischemic symptoms.

PubMed

Nara, Mizuho; Komatsuda, Atsushi; Fujishima, Masumi; Fujishima, Naohito; Nara, Miho; Iino, Takako; Ito, Hiroshi; Sawada, Ken-ichi; Wakui, Hideki

2011-08-01

A 22-year-old woman, who often carried heavy books, was admitted for evaluation of hyperreninemic hypertension. Two months prior to admission, she noted leg edema. Radiological examinations revealed bilateral renal infarction with no other abnormal findings. An echocardiography showed a patent foramen ovale (PFO). Hypertension was considered secondary to renal infarction caused by paradoxical embolism through PFO. Antihypertensive and anticoagulant therapy led to improvement of hypertension. In previously reported cases of renal paradoxical embolism, multiorgan involvement was usually observed. Our case is unique in that embolism was confirmed only in the kidneys, and that clinical characteristics of renal embolism were not observed.

Bolzano`s Approach to the Paradoxes of Infinity: Implications for Teaching

NASA Astrophysics Data System (ADS)

Waldegg, Guillermina

2005-08-01

In this paper we analyze excerpts of Paradoxes of the Infinite, the posthumous work of Bernard Bolzano (1781-1848), in order to show that Georg Cantor‘s (1845-1918) approach to the problem of defining actual mathematical infinity is not the most natural. In fact, Bolzano‘s approach to the paradoxes of infinity is more intuitive, while remaining internally coherent. Bolzano‘s approach, however, had limitations. We discuss implications for teaching, which include a better understanding of the responses of students to situations involving actual mathematical infinity, for it is possible to draw a kind of parallel between these responses and Bolzano‘s reasoning.

Native intra- and inter-specific reactions may cause the paradox of pest control with harvesting.

PubMed

Seno, Hiromi

2010-05-01

We analyse a general time-discrete mathematical model of host-parasite population dynamics with harvesting, in which the host can be regarded as a pest. We harvest a portion of the host population at a moment in each year. Our model involves the density effect on the host population. We investigate the condition in which the harvesting of the host results in a paradoxical increase of its equilibrium population size. Our results imply that for a family of pest-enemy systems, the paradox of pest control could be caused essentially by the interspecific relationship and the intraspecific density effect.

The Obesity Paradox: A Misleading Term That Should Be Abandoned.

PubMed

Flegal, Katherine M; Ioannidis, John P A

2018-04-01

The term "obesity paradox" is a figure of speech, not a scientific term. The term has no precise definition and has been used to describe numerous observations that have little in common other than the finding of an association of obesity with a favorable outcome. The terminology has led to misunderstandings among researchers and the public alike. It's time for authors and editors to abandon the use of this term. Simply labeling counterintuitive findings as the "obesity paradox" adds no value. Unexpected findings should not be viewed negatively; such findings can lead to new knowledge, better treatments, and scientific advances. © 2018 The Obesity Society.

Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids

PubMed Central

2011-01-01

Background The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Results Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). Conclusion These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism. PMID:22018327

Changes in cholesterol homeostasis modify the response of F1B hamsters to dietary very long chain n-3 and n-6 polyunsaturated fatty acids.

PubMed

Lecker, Jaime L; Matthan, Nirupa R; Billheimer, Jeffrey T; Rader, Daniel J; Lichtenstein, Alice H

2011-10-21

The plasma lipoprotein response of F1B Golden-Syrian hamsters fed diets high in very long chain (VLC) n-3 polyunsaturated fatty acids (PUFA) is paradoxical to that observed in humans. This anomaly is attributed, in part, to low lipoprotein lipase activity and is dependent on cholesterol status. To further elucidate the mechanism(s) for these responses, hamsters were fed diets containing supplemental fish oil (VLC n-3 PUFA) or safflower oil (n-6 PUFA) (both 10% [w/w]) and either cholesterol-supplemented (0.1% cholesterol [w/w]) or cholesterol-depleted (0.01% cholesterol [w/w] and 10 days prior to killing fed 0.15% lovastatin+2% cholestyramine [w/w]). Cholesterol-supplemented hamsters fed fish oil, relative to safflower oil, had higher non-high density lipoprotein (HDL) cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic low density lipoprotein (LDL) receptor, sterol regulatory element binding protein (SREBP)-1c and acyl-CoA: cholesterol acyl transferase-2 (ACAT) mRNA and protein (p < 0.05), and higher hepatic apolipoprotein (apo) B-100 and apo E protein levels. In contrast, cholesterol-depleted hamsters fed fish oil, relative to safflower oil, had lower non-HDL cholesterol and triglyceride concentrations (P < 0.001) which were associated with lower hepatic SREBP-1c (p < 0.05) but not apo B-100, apo E or ACAT-2 mRNA or protein levels. Independent of cholesterol status, fish oil fed hamsters had lower HDL cholesterol concentrations (p < 0.001), which were associated with lower hepatic apoA-I protein levels (p < 0.05). These data suggest disturbing cholesterol homeostasis in F1B hamsters alters their response to dietary fatty acids, which is reflected in altered plasma lipoprotein patterns and regulation of genes associated with their metabolism.

Rock mechanics evaluation of potential repository sites in the Paradox, Permian, and Gulf Coast Basins: Volume 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-09-01

Thermal and thermomechanical analyses of a conceptual radioactive waste repository containing commercial and defense high-level wastes and spent fuel have been performing using finite element models. The thermal and thermomechanical responses of the waste package, disposal room, and repository regions were evaluated. four bedded salt formations, in Davis and Lavender Canyons in the Paradox Basin of southeastern Utah and in Deaf Smith and Swisher counties in the Permian Basin of northwestern Texas, and three salt domes, Vacherie Dome in northwestern Louisiana and Richton and Cypress Creek Domes in southeastern Mississippi, located in the Gulf Coast Basin, were examined. In themore » Paradox Basin, the pressure exerted on the waste package overpack was much greater than the initial in situ stress. The disposal room closure was less than 10 percent after 5 years. Surface uplift was nominal, and no significant thermomechanical perturbation of the aquitards was observed. In the Permian Basin, the pressure exerted on the waste package overpack was greater than the initial in situ stress. The disposal room closures were greater than 10 percent in less than 5 years. Surface uplift was nominal, and no significant thermomechanical perturbation of the aquitards was observed. In the Gulf Coast Basin, the pressure exerted on the waste package overpack was greater than the initial in situ stress. The disposal room closures were greater than 10 percent in less than 5 years. No significant thermomechanical perturbation of the overlying geology was observed. 40 refs., 153 figs., 32 tabs.« less

DDT and Malaria Prevention: Addressing the Paradox

PubMed Central

Bouwman, Hindrik; van den Berg, Henk; Kylin, Henrik

2011-01-01

Background The debate regarding dichlorodiphenyltrichloroethane (DDT) in malaria prevention and human health is polarized and can be classified into three positions: anti-DDT, centrist-DDT, pro-DDT. Objective We attempted to arrive at a synthesis by matching a series of questions on the use of DDT for indoor residual spraying (IRS) with literature and insights, and to identify options and opportunities. Discussion Overall, community health is significantly improved through all available malaria control measures, which include IRS with DDT. Is DDT “good”? Yes, because it has saved many lives. Is DDT safe as used in IRS? Recent publications have increasingly raised concerns about the health implications of DDT. Therefore, an unqualified statement that DDT used in IRS is safe is untenable. Are inhabitants and applicators exposed? Yes, and to high levels. Should DDT be used? The fact that DDT is “good” because it saves lives, and “not safe” because it has health and environmental consequences, raises ethical issues. The evidence of adverse human health effects due to DDT is mounting. However, under certain circumstances, malaria control using DDT cannot yet be halted. Therefore, the continued use of DDT poses a paradox recognized by a centrist-DDT position. At the very least, it is now time to invoke precaution. Precautionary actions could include use and exposure reduction. Conclusions There are situations where DDT will provide the best achievable health benefit, but maintaining that DDT is safe ignores the cumulative indications of many studies. In such situations, addressing the paradox from a centrist-DDT position and invoking precaution will help design choices for healthier lives. PMID:21245017

Underlying Paradox in the European Union's Multilingualism Policies

ERIC Educational Resources Information Center

Johnson, Fern L.

2013-01-01

The European Union (EU) has developed comprehensive policies in recent years to promote multilingualism. In this article, major EU policy statements on multilingualism are analyzed to demonstrate how their underlying language ideology produces paradox by both encouraging multilingualism and regulating its definition within the EU. The first…

Twin Paradox: A Complete Treatment from the Point of View of Each Twin.

ERIC Educational Resources Information Center

Perrin, Robert

1979-01-01

Modifies and expands on the treatment of the twin paradox by solving the gravitational field equations and geodesic equations of motion in the traveling twin's reference frame, thus determining the time elapsed on the Earth during the periods of acceleration. (Author/GA)

DETECTION AND IMPLICATIONS OF EARLY AGROBACTERIUM TUMEFACIENS INFECTION OF PARADOX SEEDS AND SEEDLINGS

USDA-ARS?s Scientific Manuscript database

Paradox (Juglans hindsii x J. regia), the dominant rootstock used in California, USA walnut production, has many desirable horticultural characteristics, but is highly susceptible to crown gall. Crown gall, caused by the soil-borne bacterium Agrobacterium tumefaciens, can not be consistently control...

Unraveling the Race Paradox of Achievement and Self-Views

ERIC Educational Resources Information Center

Eccleston, Collette P.; Smyth, Joshua M.; Lopoo, Leonard M.

2010-01-01

Considerable evidence indicates that African American students achieve less academically than European American students. Yet, African American students hold more positive self-views than their European American counterparts. Previous studies that address these seemingly paradoxical findings focus on students in a relatively narrow age range…

Simpson's Paradox in the Interpretation of "Leaky Pipeline" Data

ERIC Educational Resources Information Center

Walton, Paul H.; Walton, Daniel J.

2016-01-01

The traditional "leaky pipeline" plots are widely used to inform gender equality policy and practice. Herein, we demonstrate how a statistical phenomenon known as Simpson's paradox can obscure trends in gender "leaky pipeline" plots. Our approach has been to use Excel spreadsheets to generate hypothetical "leaky…

The Paradox of Being a Woman Teacher.

ERIC Educational Resources Information Center

Tamboukou, Maria

2000-01-01

Examines discourses that interweave women's position in education today, theorizing education as a nexus of created paradoxical spaces, where the female self attempts to surpass closed boundaries, questioning the dichotomy of the feminized private and/or masculine public. Considers the importance of time restrictions upon women's lives. Discusses…

Paradox as a Therapeutic Technique: A Review

ERIC Educational Resources Information Center

Soper, Patricia H.; L'Abate Luciano

1977-01-01

The increasing use of paradoxical messages and injunctions in marital and familial therapies is reviewed. The theoretical, empirical, and clinical grounds for this practice, on the basis of this review, are still incomplete and questionable. The need for empirical research in this area is still great. (Author)

A Psychological Taxonomy of Organizational Innovation: Resolving the Paradoxes

ERIC Educational Resources Information Center

Cropley, David; Cropley, Arthur

2012-01-01

The process of innovation involves numerous contradictions not adequately addressed by business-oriented approaches, in particular the problem that what seem to be mutually antagonistic factors are involved. Psychological research on creativity, especially the 4 "Ps" (process, person, product, and press) and the paradoxes of creativity…

The 'obesity paradox' does exist in patients undergoing transcatheter aortic valve implantation for aortic stenosis: a systematic review and meta-analysis.

PubMed

Lv, Wenyu; Li, Shuangjiang; Liao, Yanbiao; Zhao, Zhengang; Che, Guowei; Chen, Mao; Feng, Yuan

2017-10-01

Most recent studies have proposed the paradoxical benefits of obesity in surgical populations. For patients who underwent transcatheter aortic valve implantation (TAVI) for aortic stenosis, the prognostic roles of obesity and high body mass index remain controversial. Therefore, the objective of this meta-analysis was to evaluate whether the 'obesity paradox' exists in patients undergoing TAVI. We searched in PubMed and EMBASE to identify the eligible articles. Odds ratios and hazard ratios with the corresponding 95% confidence intervals (CI) were adopted for synthesizing short-term and long-term survival outcomes, respectively. The level of heterogeneity and the publication bias between studies were also estimated. Finally, there were 16 studies with 12 330 patients who met the eligibility criteria and who were thus included in this review. When body mass index was analysed as a continuous variable, each increase of 1 kg/m2 was significantly associated with the lower 30-day mortality rate (odds ratio = 0.95; 95% CI = 0.93-0.97; P < 0.001) and better long-term overall survival (hazard ratio = 0.96; 95% CI = 0.94-0.97; P < 0.001) for patients undergoing TAVI. The obese patients had a significantly lower risk of 30-day mortality after TAVI than did normal patients (odds ratio = 0.69; 95% CI = 0.50-0.95; P = 0.024). Further analyses indicated that the obesity could be predictive of more favourable long-term overall survival of TAVI (hazard ratio = 0.84; 95% CI = 0.72-0.97; P = 0.021). However, we found no difference in procedural complications between the obese and normal patients. In conclusion, higher body mass index and obesity seem to have protective benefits on both short-term and long-term survival of TAVI patients. Current evidence suggests that the 'obesity paradox' may really exist in TAVI. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The Quantized Geometry of Visual Space: The Coherent Computation of Depth, Form, and Lightness. Revised Version.

DTIC Science & Technology

1982-08-01

of sensitivity with background luminance, and the finitE capacity of visual short term memory are discussed in terms of a small set of ...binocular rivalry, reflectance rivalry, Fechner’s paradox, decrease of threshold contrast with increased number of cycles in a grating pattern, hysteresis...adaptation level tuning, Weber law modulation, shift of sensitivity with background luminance, and the finite capacity of visual