344 research outputs found

    Retention of Capable New Employees under Uncertainty: Impact of Strategic Interactions

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    We study a game involving a firm and a newly hired employee whose capability is initially unknown to both parties. Both players observe the performance of the employee and update their common posterior beliefs about the employee’s capability. The learning process presents each party with an option: the firm can terminate an incapable employee, and a capable employee can leave the firm for greater financial remuneration elsewhere. To understand the impact of this noncooperative interaction, we examine the Markov perfect equilibrium termination strategies and payoffs that unfold. We find that in the region of sufficiently high learning rates, reducing the rate of learning can increase the equilibrium payoff for both parties. Slower learning prolongs the employment because more performance outcomes must be observed to fully assess the employee’s capability. In the region of sufficiently slow learning rates, reducing the rate of learning can benefit the firm if the employee is deemed capable but hurt the firm otherwise. Our result identifies a nonfinancial way for firms to improve retention of capable new employees

    Prostate-specific extracellular vesicles as a novel biomarker in human prostate cancer

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    Extracellular vesicles (EVs) may play an important role in cancer development and progression. We aimed to investigate the prognostic potential of prostate-specific EVs in prostate cancer (PCa) patients. Plasma and prostate tissue were collected from patients who underwent surgery for PCa (n = 82) or benign prostatic hyperplasia (BPH, n = 28). To analyze the quantity of EVs in prostate, we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and prostate-specific membrane antigen (PSMA), and immunofluorescence staining. After EV isolation from plasma, CD63 and PSMA concentration was measured using ELISA kits. PSMA-positive areas in prostate differed in patients with BPH, and low-, intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p < 0.001). Plasma PSMA-positive EV concentration differed in patients with BPH, and low-, intermediate-, and high-risk PCa (21.9, 43.4, 49.2, 59.9 ng/mL, p < 0.001), and ROC curve analysis indicated that plasma PSMA-positive EV concentration differentiated PCa from BPH (AUC 0.943). Patients with lower plasma PSMA-positive EV concentration had greater prostate volume (50.2 vs. 33.4 cc, p < 0.001) and lower pathologic Gleason score (p = 0.025). During the median follow-up of 18 months, patients with lower plasma PSMA-positive EV concentration tended to have a lower risk of biochemical failure than those with higher levels of prostate-specific EVs (p = 0.085).11910Ysciescopu

    Dynamic response of existing steel frames with masonry infills under multiple earthquakes

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    Existing steel moment-resisting frames in several seismic regions worldwide are often characterised by high vulnerability to earthquakes due to insufficient local and/or global ductility. Therefore, it is of paramount importance to assess their response under strong motions and provide cost-effective retrofitting remedies. However, the current code-based assessment framework utilized in Europe for assessing existing structures is inadequate and requires improvement, especially to account for the contribution of masonry infills as they significantly influence the seismic response of steel buildings. To this end, the H2020-INFRAIA-SERA project HITFRAMES (i.e., Hybrid Testing of an Existing Steel Frame with Infills under Multiple Earthquakes) aims at experimental evaluation of a case study building representative of non-seismically designed European steel frames. This paper presents the dynamic response analyses of the case study building and serves as a theoretical prediction of the experimental results for HTTFRAMES. The case study building is analysed as a bare, an infilled and a retrofitted frame with buckling restrained braces (BRBs), respectively. It is subjected to the natural seismic sequence recorded during the 2016-2017 Central Italy earthquakes. The modal properties of the case study building are determined first, followed by the investigation of its non-linear dynamic response. The dynamic tests are performed with the earthquake records scaled to different intensity levels to simulate the structural performance under different limit states according to Eurocode 8-Part 3. The impact of masonry infills and BRB-retrofit is also investigated by comparing the response of models with different configurations. It can be concluded that appropriately-designed BRBs are effective in protecting steel frames from experiencing critical damage during earthquakes and reducing significantly the transient and residual drift

    Translation initiation mediated by RNA looping

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    Eukaryotic translation initiation commences at the initiation codon near the 5&apos; end of mRNA by a 40S ribosomal subunit, and the recruitment of a 40S ribosome to an mRNA is facilitated by translation initiation factors interacting with the m7G cap and/or poly (A) tail. The 40S ribosome recruited to an mRNA is then transferred to the AUG initiation codon with the help of translation initiation factors. To understand the mechanism by which the ribosome finds an initiation codon, we investigated the role of eIF4G in finding the translational initiation codon. An artificial polypeptide eIF4G fused with MS2 was localized downstream of the reporter gene through MS2-binding sites inserted in the 3&apos; UTR of the mRNA. Translation of the reporter was greatly enhanced by the eIF4G-MS2 fusion protein regardless of the presence of a cap structure. Moreover, eIF4G-MS2 tethered at the 3&apos; UTR enhanced translation of the second cistron of a dicistronic mRNA. The encephalomyocarditis virus internal ribosome entry site, a natural translational-enhancing element facilitating translation through an interaction with eIF4G, positioned downstream of a reporter gene, also enhanced translation of the upstream gene in a cap-independent manner. Finally, we mathematically modeled the effect of distance between the cap structure and initiation codon on the translation efficiency of mRNAs. The most plausible explanation for translational enhancement by the translational-enhancing sites is recognition of the initiation codon by the ribosome bound to the ribosome-recruiting sites through "RNA looping." The RNA looping hypothesis provides a logical explanation for augmentation of translation by enhancing elements located upstream and/or downstream of a protein-coding region.open112122sciescopu

    The effectiveness of moxibustion for the treatment of functional constipation: a randomized, sham-controlled, patient blinded, pilot clinical trial

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    <p>Abstract</p> <p>Background</p> <p>Moxibustion is an ancient traditional medicine using burning mugworts to stimulate acupuncture points. The aim of this study was to investigate the safety and efficacy of moxibustion for the treatment of constipation using a randomized, sham-controlled, participant-blinded, pilot trial.</p> <p>Methods</p> <p>Twenty-six participants (identified with either qi (vital energy) deficiency or qi excess syndrome) were randomly divided into either a moxibustion or sham group. Participants were treated with real or sham moxibustion at 4 acupuncture points, ST23 and ST27, bilaterally, 3 times per week for four weeks. The primary outcome was the frequency of defecations; secondary outcomes were the Bristol stool form scale (BSS) and the constipation assessment scale (CAS).</p> <p>Results</p> <p>Of the 26 participants that were randomized, 24 completed the study. Defecation frequency, BSS, and CAS showed no difference between the moxibustion and sham groups. The differences were -0.25 (95% CI: -2.08, 1.58, p = 0.78), -1.22 (95% CI: -2.7, 0.26, p = 0.1), 0.91 (95% CI: -1.46, 3.28, p = 0.44) in defecation frequency, BSS, CAS, respectively. The defecation frequency increased from an average of 3.3 to 4.6 times per week in the moxibustion group (1.5[-0.5, 2], <it>p </it>= 0.06) and from 2.7 to 3.7 stools per week in the sham group (1[-1, 2], <it>p </it>= 0.15) after four weeks of treatment. The difference between participants with a deficiency or an excess syndrome, determined based on assessment of sweat, facial features, pain, body energy, and pulse type, was significant in only defecation frequency. The difference was 3.3 (95% CI: 0.41, 6.19, <it>p </it>= 0.03).</p> <p>Conclusion</p> <p>Moxibustion treatment appears safe, but showed no positive effect on constipation. The effectiveness of moxibustion treatment may depend on the syndrome pattern, and further long-term studies with a larger number of subjects are warranted.</p> <p>Trial registration</p> <p>Clinical Research Information Service, KCT0000168</p

    Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis

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    Langerhans cell histiocytosis is a rare group of proliferative disorders. Beside cutaneous involvement, other internal organs can be affected. The treatment of cutaneous lesions is difficult and relies on topical corticosteroids, carmustine, nitrogen mustard, and photochemotherapy. Systemic steroids and vinblastine are used for recalcitrant skin lesions. However, some cases fail to respond. An 18-month old boy presented a CD1a+, S100a+ Langerhans cell histocytosis with cutaneous and severe scalp involvement. Topical corticosteroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and vinblastine improved the truncal involvement but had no effect on the scalp lesions. Methylaminolevulinate (MAL) based photodynamic therapy (PDT) resulted in a significant regression of the scalp lesions. Control histology revealed an almost complete clearance of the tumor infiltrate. Clinical follow-up after six months showed no recurrence

    Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

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    The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

    Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A

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    <p>Abstract</p> <p>Background</p> <p>Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population.</p> <p>Objective</p> <p>In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus.</p> <p>Methods</p> <p>Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter.</p> <p>Results</p> <p>Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8<sup>+ </sup>T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4<sup>+</sup>/CD8<sup>+</sup>) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (<it>P </it>< 0.05). There was similar genotypic distribution in both acute and fulminant category, with predominance of genotype IIIA (70%) compared to IA (30%).</p> <p>Conclusions</p> <p>Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity.</p

    Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

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    We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
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