Spitzer Observations of Var Her 04: Possible Detection of Dust Formation in a Super-Outbursting TOAD

We present four MIPS (24 \micron) and two IRAC (3.6, 4.5, 5.8, and 8.0 \micron) Spitzer observations of the newly discovered Tremendous Outburst Amplitude Dwarf nova (TOAD) Var Her 04 during decline from super-outburst. The four MIPS observations span 271 days and the two IRAC observations span 211 days. Along the line-of-sight to Var Her 04, there is a foreground M-star within 1\arcsec of the variable; as a result, all of the Spitzer photometry presented in this paper is a blend of the foreground M-star and Var Her 04. We estimate the quiescent level of the TOAD to be $\Delta V=4-5$ magnitudes below that of the M-star. Based upon the spectral energy distribution and the 2MASS colors, we find the M-star to be an M3.5V dwarf at a distance of 80-130 pc. Based upon its outburst amplitude and quiescent apparent magnitude, we estimate the distance to Var Her 04 to be 200-400 pc, suggesting that the line-of-sight foreground star is physically unrelated to the cataclysmic variable. All of the Spitzer photometry is consistent with the photospheric emission of the line-of-sight M3.5V star, except for one 24 \micron observation obtained after the variable re-brightened. This 24 \micron flux density is 75 $\mu$Jy ($4\sigma$) above the preceding and following MIPS observations. We tentatively suggest that the mid-infrared brightening of 75 $\mu$Jy may be associated with a dust formation event in the super-outburst ejecta. Assuming a dust temperature of 100-400 K, we have estimated the amount of dust required. We find $10^{-13}-10^{-11}$ M$_\odot$ of dust is needed, consistent with amounts of mass ejection in TOADs expected during super-outburst, and possibly making TOADs important contributors to the recycling of the interstellar medium.Comment: Accepted for publication in The Astronomical Journa

Near to Mid-infrared Spectroscopy of (65803) Didymos as Observed by JWST: Characterization Observations Supporting the Double Asteroid Redirection Test

The Didymos binary asteroid was the target of the Double Asteroid Redirection Test (DART) mission, which intentionally impacted Dimorphos, the smaller member of the binary system. We used the Near-Infrared Spectrograph and Mid-Infrared Instrument instruments on JWST to measure the 0.6–5 and 5–20 μm spectra of Didymos approximately two months after the DART impact. These observations confirm that Didymos belongs to the S asteroid class and is most consistent with LL chondrite composition, as was previously determined from its 0.6–2.5 μm reflectance spectrum. Measurements at wavelengths >2.5 μm show Didymos to have thermal properties typical for an S-complex asteroid of its size and to be lacking absorptions deeper than ∼2% due to OH or H2O. Didymos’ mid-infrared emissivity spectrum is within the range of what has been measured on S-complex asteroids observed with the Spitzer Space Telescope and is most consistent with emission from small (<25 μm) surface particles. We conclude that the observed reflectance and physical properties make the Didymos system a good proxy for the type of ordinary chondrite asteroids that cross near-Earth space, and a good representative of likely future impactors

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10 ) and AC058822.1 (P = 1.47 × 10 ), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10 ), demonstrating the importance of diversifying study cohorts. [Abstract copyright: © 2023. The Author(s).

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Participation in Active Singing Leads to Cognitive Improvements in Individuals With Dementia

Present study aims to examine effect of music in cognitive improvements in individuals with dementia. Music has been shown to be an effective management strategy for individuals with Alzheimer’s disease and has been shown to reduce agitation, antisocial behavior, depression, aggression, and anxiety. Thus, the effect of active singing on measures of cognition and life satisfaction was examined. The study was performed at an east coast assisted living facility. Singing and listening groups (N = 45) received three vocal music sessions per week. Vocal music programming included familiar (nostalgic) and nonfamiliar (novel) vocal music selections in four, 50-minute singing programs. Music has been shown to be an effective management strategy for individuals with Alzheimer’s disease and has been shown to reduce agitation, antisocial behavior, depression, aggression, and anxiety. Thus, the effect of active singing on measures of cognition and life satisfaction was examined. (PsycINFO Database Record (c) 2016 APA, all rights reserved

The Effects of Fetal Surgery on Retinopathy of Prematurity Development

Background: Fetal surgery is selectively offered for severe or life-threatening fetal malformations. These infants are often born prematurely and are thus at risk for retinopathy of prematurity (ROP). It is not known whether fetal surgery confers an increased risk of developing severe ROP relative to published rates in standard premature populations ≤37 weeks of age grouped by birth weight

The effects of Fetal Surgery on Retinopathy of Prematurity Development

Background Fetal surgery is selectively offered for severe or life-threatening fetal malformations. These infants are often born prematurely and are thus at risk for retinopathy of prematurity (ROP). It is not known whether fetal surgery confers an increased risk of developing severe ROP relative to published rates in standard premature populations ≤37 weeks of age grouped by birth weight (<1500 grams or ≥1500 grams). Design This is a retrospective chart review. Methods We reviewed the charts of 137 patients who underwent open fetal/fetoscopic surgery from 1996–2004. Surgical indications included twin-twin transfusion syndrome (TTTS), myelomeningocele (MMC), congenital diaphragmatic hernia (CDH), sacrococcygeal teratoma (SCT), cystic adenomatoid malformation of the lung (CCAM), and twin reversed arterial perfusion sequence (TRAP). Of these, 17 patients had local ROP examination data. Binomial tests were performed to assess whether rates of ROP in our fetal/fetoscopic surgery cohort were significantly different from published rates. Results There were 5 patients each with an underlying diagnosis of TTTS and MMC, 2 patients each with CDH and TRAP, and 1 patient each with SCT, CCAM, and mediastinal teratoma. The mean gestational age at surgery was 23 4 / 7 ± 2 3 / 7 weeks, mean gestational age at birth was 30 ± 2 5 / 7 weeks, and mean birth weight was 1449 ± 510 grams (610–2485). Compared to published rates of ROP and threshold ROP, our fetal surgery patients had significantly higher rates of ROP and threshold ROP in both the <1500 grams and the ≥1500 grams group (all p-values <0.05). Conclusions Fetal/fetoscopic surgery appears to significantly increase the rate of ROP and threshold ROP development. Greater numbers are needed to confirm these observations

Congenital diaphragmatic hernia in 22q11.2 deletion syndrome.

We report the important association of congenital diaphragmatic hernia (CDH) and 22q11.2 deletion syndrome (22q11.2DS). The prevalence of CDH in our cohort of patients with 22q11.2DS is 0.8% (10/1246), which is greater than in the general population (0.025%). This observation suggests that 22q11.2DS should be considered when a child or fetus presents with CDH, in particular when other clinical findings associated with the 22q11.2DS are present, such as congenital cardiac defects. Furthermore, this finding may lead to the identification of an additional locus for diaphragmatic hernia in the general population. © 2016 Wiley Periodicals, Inc

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Background: low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: we evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: in European ancestry samples, 14 genes were significantly associated (q &lt; 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1 (P = 1.47 × 10-4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10-5), demonstrating the importance of diversifying study cohorts.</p