437 research outputs found

    Comparing Income Distributions Between Economies That Reward Innovation And Those That Reward Knowledge

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    In this paper, we develop an optimal control model of labor allocation in two types of economy - one economy is for innovative workers and the other one for knowledge workers. In both economies, workers allocate time between learning and discovering new knowledge. Both markets consist of a continuum of heterogeneous agents that are distinguished by their learning ability. Workers are rewarded for the knowledge they possess in the knowledge economy, and only for the new knowledge they create in the innovative economy. We show that, at steady state, while human capital accumulation is higher in the knowledge economy, the rate of knowledge creation is not necessarily higher in the innovative economy. Secondly, we prove that when the cost of learning is sufficiently high, the distribution of net wage income in the knowledge economy dominates that in the innovative economy in the first degree.

    Viperin interacts with PEX19 to mediate peroxisomal augmentation of the innate antiviral response.

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    Peroxisomes are recognized as significant platforms for the activation of antiviral innate immunity where stimulation of the key adapter molecule mitochondrial antiviral signaling protein (MAVS) within the RIG-I like receptor (RLR) pathway culminates in the up-regulation of hundreds of ISGs, some of which drive augmentation of multiple innate sensing pathways. However, whether ISGs can augment peroxisome-driven RLR signaling is currently unknown. Using a proteomics-based screening approach, we identified Pex19 as a binding partner of the ISG viperin. Viperin colocalized with numerous peroxisomal proteins and its interaction with Pex19 was in close association with lipid droplets, another emerging innate signaling platform. Augmentation of the RLR pathway by viperin was lost when Pex19 expression was reduced. Expression of organelle-specific MAVS demonstrated that viperin requires both mitochondria and peroxisome MAVS for optimal induction of IFN-β. These results suggest that viperin is required to enhance the antiviral cellular response with a possible role to position the peroxisome at the mitochondrial/MAM MAVS signaling synapse, furthering our understanding of the importance of multiple organelles driving the innate immune response against viral infection

    Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

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    It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

    Characterization of Membrane Potential Dependency of Mitochondrial Ca2+ Uptake by an Improved Biophysical Model of Mitochondrial Ca2+ Uniporter

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    Mitochondrial Ca2+ uniporter is the primary influx pathway for Ca2+ into respiring mitochondria, and hence plays a key role in mitochondrial Ca2+ homeostasis. Though the mechanism of extra-matrix Ca2+ dependency of mitochondrial Ca2+ uptake has been well characterized both experimentally and mathematically, the mechanism of membrane potential (ΔΨ) dependency of mitochondrial Ca2+ uptake has not been completely characterized. In this paper, we perform a quantitative reevaluation of a previous biophysical model of mitochondrial Ca2+ uniporter that characterized the possible mechanism of ΔΨ dependency of mitochondrial Ca2+ uptake. Based on a model simulation analysis, we show that model predictions with a variant assumption (Case 2: external and internal Ca2+ binding constants for the uniporter are distinct), that provides the best possible description of the ΔΨ dependency, are highly sensitive to variation in matrix [Ca2+], indicating limitations in the variant assumption (Case 2) in providing physiologically plausible description of the observed ΔΨ dependency. This sensitivity is attributed to negative estimate of a biophysical parameter that characterizes binding of internal Ca2+ to the uniporter. Reparameterization of the model with additional nonnengativity constraints on the biophysical parameters showed that the two variant assumptions (Case 1 and Case 2) are indistinguishable, indicating that the external and internal Ca2+ binding constants for the uniporter may be equal (Case 1). The model predictions in this case are insensitive to variation in matrix [Ca2+] but do not match the ΔΨ dependent data in the domain ΔΨ≤120 mV. To effectively characterize this ΔΨ dependency, we reformulate the ΔΨ dependencies of the rate constants of Ca2+ translocation via the uniporter by exclusively redefining the biophysical parameters associated with the free-energy barrier of Ca2+ translocation based on a generalized, non-linear Goldman-Hodgkin-Katz formulation. This alternate uniporter model has all the characteristics of the previous uniporter model and is also able to characterize the possible mechanisms of both the extra-matrix Ca2+ and ΔΨ dependencies of mitochondrial Ca2+ uptake. In addition, the model is insensitive to variation in matrix [Ca2+], predicting relatively stable physiological operation. The model is critical in developing mechanistic, integrated models of mitochondrial bioenergetics and Ca2+ handling

    The impact of muscle relaxation techniques on the quality of life of cancer patients, as measured by the FACT-G questionnaire

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    Introduction Patients with cancer frequently suffer from emotional distress, characterized by psychological symptoms such as anxiety or depression. The presence of psychological symptoms combined with the complex nature of oncology processes can negatively impact patients' quality of life. We aimed to determine the impact of a relaxation protocol on improving quality of life in a sample of oncological patients treated in the Spanish National Public Health System. Materials and methods We conducted a multicenter interventional study without a control group. In total, 272 patients with different oncologic pathologies and showing symptoms of anxiety were recruited from 10 Spanish public hospitals. The intervention comprised abbreviated progressive muscle relaxation training, according to Bernstein and Borkovec. This was followed by weekly telephone calls to each patient over a 1-month period. We collected sociodemographic variables related to the disease process, including information about mental health and the intervention. Patients' quality of life was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. Bivariate and univariate analyses were performed, along with an analysis of multiple correspondences to identify subgroups of patients with similar variations on the FACT-G. Results Patients showed statistically significant improvements on the FACT-G overall score (W = 16806; p<0.001), with an initial mean score of 55.33±10.42 and a final mean score of 64.49±7.70. We also found significant improvements for all subscales: emotional wellbeing (W = 13118; p<0.001), functional wellbeing (W = 16155.5; p<0.001), physical wellbeing (W = 8885.5; p<0.001), and social and family context (W = ?1840; p = 0.037). Conclusions Patients with cancer who learned and practiced abbreviated progressive muscle relaxation experienced improvement in their perceived quality of life as measured by the FACT-G. Our findings support a previous assumption that complementary techniques (including relaxation techniques) are effective in improving the quality of life of patients with cancer

    cExternal beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

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    <p>Abstract</p> <p>Background</p> <p>To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer.</p> <p>Methods</p> <p>125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n = 66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n = 59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes.</p> <p>Results</p> <p>The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p = 0.664 and p = 0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment.</p> <p>Conclusion</p> <p>Prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes.</p

    Does Jacobson's relaxation technique reduce consumption of psychotropic and analgesic drugsin cancer patients? A multicenter pre-post intervention study

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    Background: Cancer patients often suffer from emotional distress as a result of the oncological process. The purpose of our study was to determine whether practice of Jacobson?s relaxation technique reduced consumption of psychotropic and analgesic drugs in a sample of cancer patients. Methods: This was a multicenter pre?post intervention design. Participants were 272 patients aged over 18 years attending 10 Spanish public hospitals with oncological pathologies and anxiety symptoms. The intervention consisted of a protocol of abbreviated progressive muscle relaxation training developed by Bernstein and Borkovec. This was followed up by telephone calls over a 1-month period. The intervention was performed between November 2014 and October 2015. Sociodemographic variables related to the oncological process, mental health variables, and intervention characteristics were measured. Results: A reduction in the consumption of psychotropic and analgesic drugs was observed throughout the follow-up period. Improvement was observed throughout the 4-week follow-up for all the parameters assessed: anxiety, relaxation, concentration, and mastery of the relaxation technique. Conclusions: The practice of abbreviated Jacobson?s relaxation technique can help to decrease the consumption of psychotropic and analgesic drugs. Patients experienced positive changes in all the evaluated parameters, at least during the 1-month follow-up. To confirm these findings, additional long-term studies are needed that include control groups. Trial registration: ISRCTN 81335752, DOI 10.1186/ISRCTN81335752 17. Date of registration: 22/11/2016 (retrospectively registered)

    Photodisintegration of 4^4He into p+t

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    The two-body photodisintegration of 4^4He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid 4^4He target. This is the first measurement of the photodisintegration of 4^4He above 0.4 GeV. The differential cross sections for the γ\gamma4^4Hept\to pt reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of 3^3He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure

    First Measurement of Beam-Recoil Observables Cx and Cz in Hyperon Photoproduction

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    Spin transfer from circularly polarized real photons to recoiling hyperons has been measured for the reactions γ+pK++Λ\vec\gamma + p \to K^+ + \vec\Lambda and γ+pK++Σ0\vec\gamma + p \to K^+ + \vec\Sigma^0. The data were obtained using the CLAS detector at Jefferson Lab for center-of-mass energies WW between 1.6 and 2.53 GeV, and for 0.85<cosθK+c.m.<+0.95-0.85<\cos\theta_{K^+}^{c.m.}< +0.95. For the Λ\Lambda, the polarization transfer coefficient along the photon momentum axis, CzC_z, was found to be near unity for a wide range of energy and kaon production angles. The associated transverse polarization coefficient, CxC_x, is smaller than CzC_z by a roughly constant difference of unity. Most significantly, the {\it total} Λ\Lambda polarization vector, including the induced polarization PP, has magnitude consistent with unity at all measured energies and production angles when the beam is fully polarized. For the Σ0\Sigma^0 this simple phenomenology does not hold. All existing hadrodynamic models are in poor agreement with these results.Comment: 28 pages, 18 figures, Submitted to Physical Review

    An AP Endonuclease 1–DNA Polymerase β Complex: Theoretical Prediction of Interacting Surfaces

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    Abasic (AP) sites in DNA arise through both endogenous and exogenous mechanisms. Since AP sites can prevent replication and transcription, the cell contains systems for their identification and repair. AP endonuclease (APEX1) cleaves the phosphodiester backbone 5′ to the AP site. The cleavage, a key step in the base excision repair pathway, is followed by nucleotide insertion and removal of the downstream deoxyribose moiety, performed most often by DNA polymerase beta (pol-β). While yeast two-hybrid studies and electrophoretic mobility shift assays provide evidence for interaction of APEX1 and pol-β, the specifics remain obscure. We describe a theoretical study designed to predict detailed interacting surfaces between APEX1 and pol-β based on published co-crystal structures of each enzyme bound to DNA. Several potentially interacting complexes were identified by sliding the protein molecules along DNA: two with pol-β located downstream of APEX1 (3′ to the damaged site) and three with pol-β located upstream of APEX1 (5′ to the damaged site). Molecular dynamics (MD) simulations, ensuring geometrical complementarity of interfaces, enabled us to predict interacting residues and calculate binding energies, which in two cases were sufficient (∼−10.0 kcal/mol) to form a stable complex and in one case a weakly interacting complex. Analysis of interface behavior during MD simulation and visual inspection of interfaces allowed us to conclude that complexes with pol-β at the 3′-side of APEX1 are those most likely to occur in vivo. Additional multiple sequence analyses of APEX1 and pol-β in related organisms identified a set of correlated mutations of specific residues at the predicted interfaces. Based on these results, we propose that pol-β in the open or closed conformation interacts and makes a stable interface with APEX1 bound to a cleaved abasic site on the 3′ side. The method described here can be used for analysis in any DNA-metabolizing pathway where weak interactions are the principal mode of cross-talk among participants and co-crystal structures of the individual components are available
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