Though people often report more physical symptoms and negative affect on days they experience a stressor, these effects are reduced for adults reporting a higher sense of purpose.
Abstract
Background
...Having a sense of purpose in life has been consistently demonstrated as a predictor of positive health outcomes, including less perceived stress, yet, little is known about the role of sense of purpose on stressful days.
Purpose
The current study investigated the sense of purpose as a moderator of stressor-related changes in daily physical symptoms, positive affect, and negative affect.
Methods
A subset of the Midlife in the United States study (n = 1949, mage: 56.4 years) reported their sense of purpose, along with up to eight daily assessments of stressors, affect, and physical symptoms. Multilevel models evaluated whether sense of purpose was associated with deviations in affect or physical symptom reporting on days when participants reported a stressor versus days when stressors did not occur.
Results
Sense of purpose was associated with higher daily positive affect, lower daily negative affect, and fewer daily physical symptoms. Compared with individuals who reported lower levels of purpose, those reporting higher levels encountered the same number of daily stressors, yet showed less of an increase in negative affect and physical symptoms on stressor days than on stressor-free days. Purpose did not predict changes in positive affect in response to daily stressors.
Conclusions
Findings provide evidence that a purposeful life may be characterized by lower negative affect and physical symptom reporting on stressful days.
MicroRNAs (miRNAs) are 18-23 nucleotide non-coding RNAs that regulate gene expression in a sequence specific manner. Little is known about the repertoire and function of miRNAs in melanoma or the ...melanocytic lineage. We therefore undertook a comprehensive analysis of the miRNAome in a diverse range of pigment cells including: melanoblasts, melanocytes, congenital nevocytes, acral, mucosal, cutaneous and uveal melanoma cells.
We sequenced 12 small RNA libraries using Illumina's Genome Analyzer II platform. This massively parallel sequencing approach of a diverse set of melanoma and pigment cell libraries revealed a total of 539 known mature and mature-star sequences, along with the prediction of 279 novel miRNA candidates, of which 109 were common to 2 or more libraries and 3 were present in all libraries.
Some of the novel candidate miRNAs may be specific to the melanocytic lineage and as such could be used as biomarkers to assist in the early detection of distant metastases by measuring the circulating levels in blood. Follow up studies of the functional roles of these pigment cell miRNAs and the identification of the targets should shed further light on the development and progression of melanoma.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The intracellular signaling molecule TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). We now report that DC-specific deletion of TRAF6 (TRAF6ΔDC) resulted, ...unexpectedly, in loss of mucosal tolerance, characterized by spontaneous development of T helper 2 (Th2) cells in the lamina propria and eosinophilic enteritis and fibrosis in the small intestine. Loss of tolerance required the presence of gut commensal microbiota but was independent of DC-expressed MyD88. Further, TRAF6ΔDC mice exhibited decreased regulatory T (Treg) cell numbers in the small intestine and diminished induction of iTreg cells in response to model antigen. Evidence suggested that this defect was associated with diminished DC expression of interleukin-2 (IL-2). Finally, we demonstrate that aberrant Th2 cell-associated responses in TRAF6ΔDC mice could be mitigated via restoration of Treg cell activity. Collectively, our findings reveal a role for TRAF6 in directing DC maintenance of intestinal immune tolerance through balanced induction of Treg versus Th2 cell immunity.
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•Dendritic cell (DC)-expressed TRAF6 is critical for small intestine immune tolerance•Spontaneous gut Th2 cell responses develop in the absence of DC-expressed TRAF6•Gut microbiota trigger small intestine autoimmunity absent DC-expressed TRAF6•DC-expressed TRAF6 controls IL-2-associated iTreg cell induction in small intestine
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Proteomic analysis of any biological system by two-dimensional gel electrophoresis (2-DE) requires high resolution and high reproducibility. The results presented here demonstrate the reproducible ...and accurate separation of rice (Oryza sativa L.) proteins using improved procedures for high resolution 2-DE, which were adapted for the separation of rice lamina proteins. Validation of this system was achieved by measuring the effects of sample preparation and biological variation on the coefficient of variation (CV) for replicate spots. The majority of experimental variation was shown to be introduced by the 2-DE technique (CV 0.26). Analysis of biological variation indicated that approximately 93–95% of spots were within a CV of 0.7. This provided a threshold value from which valid differences in expression between experimental groups could be screened. This system was then utilized for the proteomic analysis of short- and long-term salt-stress-responsive proteins in the rice leaf lamina. Analysis resulted in the separation of approximately 2500 protein species of which 32 were observed to be significantly regulated by salinity; so far 11 of these proteins have been identified by tandem mass spectrometry. An increase in eight proteins, including RuBisCO activase and ferritin, occurred by 24 h of exposure to sodium chloride (50 mM) and continued to increase during the following 6 d. Only one protein, a putative phosphoglycerate kinase, was found to increase in expression within 24 h and did not increase over a longer period of exposure to salt. There were also proteins that showed no change 24 h after exposure to salt, but had increased (superoxide dismutase) or decreased (S-adenosyl-L-methionine synthetase) after 7 d salt treatment.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We examine gated-Geiger mode operation of an integrated waveguide-coupled Ge-on-Si lateral avalanche photodiode (APD) and demonstrate single photon detection at low dark count for this mode of ...operation. Our integrated waveguide-coupled APD is fabricated using a selective epitaxial Ge-on-Si growth process resulting in a separate absorption and charge multiplication (SACM) design compatible with our silicon photonics platform. Single photon detection efficiency and dark count rate is measured as a function of temperature in order to understand and optimize performance characteristics in this device. We report single photon detection of 5.27% at 1310 nm and a dark count rate of 534 kHz at 80 K for a Ge-on-Si single photon avalanche diode. Dark count rate is the lowest for a Ge-on-Si single photon detector in this range of temperatures while maintaining competitive detection efficiency. A jitter of 105 ps was measured for this device.
Abstract Background Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC). Objective Report long-term outcomes of patients ...with MIBC treated by TMT. Design, setting, and participants Four hundred and seventy-five patients with cT2–T4a MIBC were enrolled on protocols or treated as per protocol at the Massachusetts General Hospital between 1986 and 2013. Intervention Patients underwent transurethral resection of bladder tumor followed by concurrent radiation and chemotherapy. Patients with less than a complete response (CR) to chemoradiation or with an invasive recurrence were recommended to undergo salvage radical cystectomy. Outcome measurements and statistical analysis Disease-specific survival (DSS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results and limitations Median follow-up for surviving patients was 7.21 yr. Five- and 10-yr DSS rates were 66% and 59%, respectively. Five- and 10-yr OS rates were 57% and 39%, respectively. The risk of salvage cystectomy at 5 yr was 29%. In multivariate analyses, T2 disease (OS hazard ratio HR: 0.57, 95% confidence interval CI: 0.44–0.75, DSS HR: 0.51, 95% CI: 0.36–0.73), CR to chemoradiation (OS HR: 0.61, 95% CI: 0.46–0.81, DSS HR: 0.49, 95% CI: 0.34–0.71), and presence of tumor-associated carcinoma in situ (OS HR: 1.56, 95% CI: 1.17–2.08, DSS HR: 1.50, 95% CI: 1.03–2.17) were significant predictors for OS and DSS. When evaluating our cohort over treatment eras, rates of CR improved from 66% to 88% and 5-yr DSS improved from 60% to 84% during the eras of 1986–1995 to 2005–2013, while the 5-yr risk of salvage radical cystectomy rate decreased from 42% to 16%. Conclusions These data demonstrate high rates of CR and bladder preservation in patients receiving TMT, and confirm DSS rates similar to modern cystectomy series. Contemporary results are particularly encouraging, and therefore TMT should be discussed and offered as a treatment option for selected patients. Patient summary Tri-modality therapy is an alternative to radical cystectomy for patients with muscle-invasive bladder cancer, and is associated with comparable long-term survival and high rates of bladder preservation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We present a wide-field optical imaging search for electromagnetic counterparts to the likely neutron star-black hole (NS-BH) merger GW190814/S190814bv. This compact binary merger was detected ...through gravitational waves by the LIGO/Virgo interferometers, with masses suggestive of an NS-BH merger. We imaged the LIGO/Virgo localization region using the MegaCam instrument on the Canada-France-Hawaii Telescope (CFHT). We describe our hybrid observing strategy of both tiling and galaxy-targeted observations, as well as our image differencing and transient detection pipeline. Our observing campaign produced some of the deepest multiband images of the region between 1.7 and 8.7 days post-merger, reaching a 5 depth of g > 22.8 (AB mag) at 1.7 days and i > 23.1 and i > 23.9 at 3.7 and 8.7 days, respectively. These observations cover a mean total integrated probability of 67.0% of the localization region. We find no compelling candidate transient counterparts to this merger in our images, which suggests that the lighter object was tidally disrupted inside of the BH's innermost stable circular orbit, the transient lies outside of the observed sky footprint, or the lighter object is a low-mass BH. We use 5 source detection upper limits from our images in the NS-BH interpretation of this merger to constrain the mass of the kilonova ejecta to be Mej 0. 015M for a "blue" ( ) kilonova and Mej 0. 04M for a "red" ( ) kilonova. Our observations emphasize the key role of large-aperture telescopes and wide-field imagers such as CFHT MegaCam in enabling deep searches for electromagnetic counterparts to gravitational-wave events.
We present experimental results for a selective epitaxially grown Ge-on-Si separate absorption and charge multiplication (SACM) integrated waveguide coupled avalanche photodiode (APD) compatible with ...our silicon photonics platform. Epitaxially grown Ge-on-Si waveguide-coupled linear mode avalanche photodiodes with varying lateral multiplication regions and different charge implant dimensions are fabricated and their illuminated device characteristics and high-speed performance is measured. We report a record gain-bandwidth product of 432 GHz for our highest performing waveguide-coupled avalanche photodiode operating at 1510nm. Bit error rate measurements show operation with BER< 10
, in the range from -18.3 dBm to -12 dBm received optical power into a 50 Ω load and open eye diagrams with 13 Gbps pseudo-random data at 1550 nm.
Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal ...blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.
Abstract
We present optical and near-infrared (NIR) (
ugriYJH
) photometry of host galaxies of Type Ia supernovae (SN Ia) observed by the
Carnegie Supernova Project-I
. We determine host galaxy ...stellar masses and, for the first time, study their correlation with SN Ia standardized luminosity across optical and NIR (
uBgVriYJH
) bands. In the individual bands, we find that SNe Ia are more luminous in more massive hosts with luminosity offsets ranging between −0.07 ± 0.03 and −0.15 ± 0.04 mag after light-curve standardization. The slope of the SN Ia Hubble residual-host mass relation is negative across all
uBgVriYJH
bands with values ranging between −0.029 ± 0.029 and −0.093 ± 0.031 mag dex
−1
—implying that SNe Ia in more massive galaxies are brighter than expected. The near-constant observed correlations across optical and NIR bands indicate that dust may not play a significant role in the observed luminosity offset–host mass correlation. We measure projected separations between SNe Ia and their host centers, and find that SNe Ia that explode beyond a projected 10 kpc have a 50%– 60% reduction of the dispersion in Hubble residuals across all bands—making them a more uniform subset of SNe Ia. Dust in host galaxies, peculiar velocities of nearby SN Ia, or a combination of both may drive this result as the color excesses of SNe Ia beyond 10 kpc are found to be generally lower than those interior, but there is also a diminishing trend of the dispersion as we exclude nearby events. We do not find that SN Ia average luminosity varies significantly when they are grouped in various host morphological types. Host galaxy data from this work will be useful, in conjunction with future high-redshift samples, in constraining cosmological parameters.
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