A polymeric dual delivery nanoscale device (DDND) was designed for combined delivery of microRNA (miR-345) and gemcitabine (GEM) to treat pancreatic cancer (PC). This temperature and pH-responsive ...pentablock copolymer system was able to restore miR-345, making xenograft tumors more susceptible to GEM, the standard therapy for PC. Restoration using DDND treatment results in sonic hedgehog signaling down regulation, which decreases desmoplasia, thereby resulting in improved GEM perfusion to the tumor and better therapeutic outcomes. The release of miR-345 and GEM could be tuned by using the DDND in the form of micelles or in the form of thermoreversible gels, based on polymer concentration. The DDNDs enabled miR-345 stability and sustained co-release of miR-345 and GEM, thereby facilitating dose-sparing use of GEM. Further, enhanced in vitro cellular uptake due to amphiphilic character, and endosomal escape because of the cationic end blocks led to efficient transfection with DDNDs. The combined DDND treatment enabled efficient reduction in cell viability of Capan-1 and CD18/HPAF cells in vitro compared with either GEM or miR-345 treatment alone. Mice carrying xenograft tumors treated with DDNDs carrying both miR-345 and GEM combination therapy displayed reduced tumor growth and less metastasis in distant organs compared to individual drug treatments. Immunohistochemical analysis of the xenograft tissues revealed significant down regulation of desmoplastic reaction, SHH, Gli-1, MUC4, and Ki67 compared to control groups.
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PurposeHealth-oriented leadership is an emerging concept that is promising for better understanding how leaders can support employee well-being. However, there is uncertainty about the process ...through which health-oriented leadership relates to employee well-being. Advancing health-oriented leadership research, this study aims to examine employee self-care and the perceived team health climate as mediating mechanisms.Design/methodology/approachThe authors conducted a time-lagged study with three measurement points (NT1 = 335, NT2 = 134, NT2 = 113) to test these mechanisms.FindingsThe results show that health-oriented leadership at Time 1 positively relates to employee self-care and perceived team health climate at Time 2, which, in turn, are negatively associated with employee exhaustion at Time 3.Originality/valueThe indirect associations suggest that health-oriented leadership relates to employee well-being via the perceived team health climate and the individuals' self-care. By revealing an important mediating mechanism, this study contributes to the health-oriented leadership literature and can help organizations and leaders improve health promotion in organizations.
SERS immunoassay biosensors hold immense potential for clinical diagnostics due to their high sensitivity and growing interest in multi-marker panels. However, their development has been hindered by ...difficulties in designing compatible extrinsic Raman labels. Prior studies have largely focused on spectroscopic characteristics in selecting Raman reporter molecules (RRMs) for multiplexing since the presence of well-differentiated spectra is essential for simultaneous detection. However, these candidates often induce aggregation of the gold nanoparticles used as SERS nanotags despite their similarity to other effective RRMs. Thus, an improved understanding of factors affecting the aggregation of RRM-coated gold nanoparticles is needed. Substituent electronic effects on particle stability were investigated using various para-substituted thiophenols. The inductive and resonant effects of functional group modifications were strongly correlated with nanoparticle surface charge and hence their stability. Treatment with thiophenols diminished the negative surface charge of citrate-stabilized gold nanoparticles, but electron-withdrawing substituents limited the magnitude of this diminishment. It is proposed that this phenomenon arises by affecting the interplay of competing sulfur binding modes. This has wide-reaching implications for the design of biosensors using thiol-modified gold surfaces. A proof-of-concept multiplexed SERS biosensor was designed according to these findings using the two thiophenol compounds with the most electron-withdrawing substitutions: NO
and CN.
The purpose of this study was to investigate which social groups are perceived as a threat target and which are perceived as a threat source during the COVID-19 outbreak. In a German sample (
N
= ...1454) we examined perceptions of social groups ranging from those that are psychologically close and smaller (family, friends, neighbors) to those that are more distal and larger (people living in Germany, humankind). We hypothesized that psychologically closer groups would be perceived as less affected by COVID-19 as well as less threatening than more psychologically distal groups. Based on social identity theorizing, we also hypothesized that stronger identification with humankind would change these patterns. Furthermore, we explored how these threat perceptions relate to adherence to COVID-19 health guidelines. In line with our hypotheses, latent random-slope modelling revealed that psychologically distal and larger groups were perceived as more affected by COVID-19 and as more threatening than psychologically closer and smaller groups. Including identification with humankind as a predictor into the threat target model resulted in a steeper increase in threat target perception patterns, whereas identification with humankind did not predict differences in threat source perceptions. Additionally, an increase in threat source perceptions across social groups was associated with more adherence to health guidelines, whereas an increase in threat target perceptions was not. We fully replicated these findings in a subgroup from the original sample (
N
= 989) four weeks later. We argue that societal recovery from this and other crises will be supported by an inclusive approach informed by a sense of our common identity as human beings.
The observation of oxygen isotopes in giant stars sheds light on mixing processes operating in their interiors. Due to the very strong correlation between nuclear burning and mixing processes it is ...very important to reduce the uncertainty on the cross sections of the nuclear reactions that are involved. In this paper we focus our attention on the reaction O18(p,γ)19F. While the O18(p,α)15N channel is thought to be dominant, the (p,γ) channel can still be an important component in stellar burning in giants, depending on the low energy cross section. So far only extrapolations from higher-energy measurements exist and recent estimates vary by orders of magnitude. These large uncertainties call for an experimental reinvestigation of this reaction. We present a direct measurement of the O18(p,γ)19F cross section using a high-efficiency 4π BGO summing detector at the Laboratory for Underground Nuclear Astrophysics (LUNA). The reaction cross section has been directly determined for the first time from 140 keV down to 85 keV and the different cross section components have been obtained individually. The previously highly uncertain strength of the 90 keV resonance was found to be 0.53 ± 0.07 neV, three orders of magnitude lower than an indirect estimate based on nuclear properties of the resonant state and a factor of 20 lower than a recently established upper limit, excluding the possibility that the 90 keV resonance can contribute significantly to the stellar reaction rate.
The 18O(p,α)15N reaction affects the synthesis of 15N, 18O and 19F isotopes, whose abundances can be used to probe the nucleosynthesis and mixing processes occurring deep inside asymptotic giant ...branch (AGB) stars. We performed a low-background direct measurement of the 18O(p,α)15N reaction cross-section at the Laboratory for Underground Nuclear Astrophysics (LUNA) from center of mass energy Ec.m.=340 keV down to Ec.m.=55 keV, the lowest energy measured to date corresponding to a cross-section of less than 1 picobarn/sr. The strength of a key resonance at center of mass energy Er=90 keV was found to be a factor of 10 higher than previously reported. A multi-channel R-matrix analysis of our and other data available in the literature was performed. Over a wide temperature range, T=0.01–1.00 GK, our new astrophysical rate is both more accurate and precise than recent evaluations. Stronger constraints can now be placed on the physical processes controlling nucleosynthesis in AGB stars with interesting consequences on the abundance of 18O in these stars and in stardust grains, specifically on the production sites of oxygen-rich Group II grains.
Workaholism and overcommitment are often used as interchangeable constructs describing an individual’s over-involvement toward their own job. Employees with high levels in both constructs are ...characterized by an excessive effort and attachment to their job, with the incapability to detach from it and negative consequences in terms of poor health and job burnout. However, few studies have simultaneously measured both constructs, and their relationships are still not clear. In this study, we try to disentangle workaholism and overcommitment by comparing them with theoretically related contextual and personal antecedents, as well as their health consequences. We conducted a nonprobability mixed mode research design on 133 employees from different organizations in Italy using both self- and other-reported measures. To test our hypothesis that workaholism and overcommitment are related yet different constructs, we used partial correlations and regression analyses. The results confirm that these two constructs are related to each other, but also outline that overcommitment (and not workaholism) is uniquely related to job burnout, so that overcommitment rather than workaholism could represent the true negative aspect of work drive. Additionally, workaholism is more related to conscientiousness than overcommitment, while overcommitment shows a stronger relationship with neuroticism than workaholism. The theoretical implications are discussed.
LArGe is a GERDA low-background test facility to study novel background suppression methods in a low-background environment, for future application in the GERDA experiment. Similar to GERDA, LArGe ...operates bare germanium detectors submersed into liquid argon (1 m3, 1.4tons), which in addition is instrumented with photomultipliers to detect argon scintillation light. The light is used in anti-coincidence with the germanium detectors to effectively suppress background events that deposit energy in the liquid argon. The background suppression efficiency was studied in combination with a pulse shape discrimination (PSD) technique using a BEGe detector for various sources, which represent characteristic backgrounds to GERDA. Suppression factors of a few times 103 have been achieved. First background data of LArGe with a coaxial HPGe detector (without PSD) yield a background index of the order 10−2 cts/(keV-kg-y), which is at the level of the GERDA phase I design goal. As a consequence of these results, the development of an active liquid argon veto in GERDA is pursued.
The NeNa and the MgAl cycles play a fundamental role in the nucleosynthesis of asymptotic giant branch stars undergoing hot bottom burning. The Na23(p,γ)24Mg reaction links these two cycles and a ...precise determination of its rate is required to correctly estimate the contribution of these stars to the chemical evolution of various isotopes of Na, Mg and Al. At temperatures of 50≲T≲110MK, narrow resonances at Ep=140 and 251keV are the main contributors to the reaction rate, in addition to the direct capture that dominates in the lower part of the temperature range. We present new measurements of the strengths of these resonances at the Laboratory for Underground Nuclear Astrophysics (LUNA). We have used two complementary detection approaches: high efficiency with a 4π BGO detector for the 140keV resonance, and high resolution with a HPGe detector for the 251keV resonance. Thanks to the reduced cosmic ray background of LUNA, we were able to determine the resonance strength of the 251keV resonance as ωγ=482(82)μeV and observed new gamma ray transitions for the decay of the corresponding state in Mg24 at Ex=11931keV. With the highly efficient BGO detector, we observed a signal for the 140keV resonance for the first time in a direct measurement, resulting in a strength of ωγ140=1.46−0.53+0.58neV (68% CL). Our measurement reduces the uncertainty of the Na23(p,γ)24Mg reaction rate in the temperature range from 0.05 to 0.1GK to at most −35%+50% at 0.07GK. Accordingly, our results imply a significant reduction of the uncertainties in the nucleosynthesis calculations.
Working in academia entails many challenges including rejections by journals, competition for funding or jobs, and uncertain job outlooks (for non-tenure staff), which can result in poor mental ...health and well-being. Previous studies have suggested self-compassion as a resource for mental health and well-being, but to date no study has been published that has tested interventions targeting self-compassion in academia. In this weekly diary study, 317 academics from Germany, Switzerland, and the US were asked to recall a negative event and were then randomly assigned to either a self-compassionate writing intervention, a three good things intervention, or an active control intervention, respectively. They also completed two surveys on four consecutive Thursdays measuring state positive and negative affect and job-related well-being (i.e., job satisfaction and work engagement). Using multi-level regression modelling, results showed that participants in the self-compassion condition reported more job satisfaction and work engagement due to experiencing less negative affect. Academics in the three good things condition showed no such effects. Results indicated that self-compassion in academia is a resource that enables emotion-oriented coping during difficult times or in challenging situations that may benefit academics’ job-related well-being. The study highlights both the importance of discussing well-being in academia and ways to strengthen it.
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