One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol

Difluoroalkenylzinc reagents prepared from 1-(2’-methoxy-ethoxymethoxy)-2,2,2-trifluoroethane and 1-(N,N-diethylcarbamoyloxy)-2,2,2-trifluoroethane at ice bath temperatures, underwent Negishi coupling with a range of aryl halides in a convenient one pot procedure. While significant differences between the enol acetal and carbamate reagents were revealed, the Negishi protocol compared very favourably with alternative coupling procedures in terms of overall yields from trifluoroethanol

Baseline T cell dysfunction by single cell network profiling in metastatic breast cancer patients.

BackgroundWe previously reported the results of a multicentric prospective randomized trial of chemo-refractory metastatic breast cancer patients testing the efficacy of two doses of TGFβ blockade during radiotherapy. Despite a lack of objective responses to the combination, patients who received a higher dose of TGFβ blocking antibody fresolimumab had a better overall survival when compared to those assigned to lower dose (hazard ratio of 2.73, p = 0.039). They also demonstrated an improved peripheral blood mononuclear cell (PBMC) counts and increase in the CD8 central memory pool. We performed additional analysis on residual PBMC using single cell network profiling (SCNP).MethodsThe original trial randomized metastatic breast cancer patients to either 1 or 10 mg/kg of fresolimumab, every 3 weeks for 5 cycles, combined with radiotherapy to a metastatic site at week 1 and 7 (22.5 Gy given in 3 doses of 7.5 Gy). Trial immune monitoring results were previously reported. In 15 patients with available residual blood samples, additional functional studies were performed, and compared with data obtained in parallel from seven healthy female donors (HD): SCNP was applied to analyze T cell receptor (TCR) modulated signaling via CD3 and CD28 crosslinking and measurement of evoked phosphorylation of AKT and ERK in CD4 and CD8 T cell subsets defined by PD-1 expression.ResultsAt baseline, a significantly higher level of expression (p < 0.05) of PD-L1 was identified in patient monocytes compared to HD. TCR modulation revealed dysfunction of circulating T-cells in patient baseline samples as compared to HD, and this was more pronounced in PD-1+ cells. Treatment with radiotherapy and fresolimumab did not resolve this dyfunctional signaling. However, in vitro PD-1 blockade enhanced TCR signaling in patient PD-1+ T cells and not in PD-1- T cells or in PD-1+ T cells from HD.ConclusionsFunctional T cell analysis suggests that baseline T cell functionality is hampered in metastatic breast cancer patients, at least in part mediated by the PD-1 signaling pathway. These preliminary data support the rationale for investigating the possible beneficial effects of adding PD-1 blockade to improve responses to TGFβ blockade and radiotherapy.Trial registrationNCT01401062

Airborne lidar detection and characterization of internal waves in a shallow fjord

A dual-polarization lidar and photography are used to sense internal waves in West Sound, Orcas Island, Washington, from a small aircraft. The airborne lidar detected a thin plankton layer at the bottom of the upper layer of the water, and this signal provides the depth of the upper layer, amplitude of the internal waves, and the propagation speed. The lidar is most effective when the polarization filter on the receiver is orthogonal to the transmitted light, but this does not depend significantly on whether the transmitted light is linearly or circularly polarized. The depolarization is greater with circular polarization, and our results are consistent with a single parameter Mueller scattering matrix. Photographs of the surface manifestation of the internal waves clearly show the propagation direction and width of the phase fronts of the internal waves, even though the contrast is low (2%). Combined with the lidar profile, the total energy of the internal wave packet was estimated to be 9 MJ

Results for the hybrid laminar flow control experiment conducted in the NASA Langley 8-foot transonic pressure tunnel on a 7-foot chord model

A description is given of the development of, and results from, the hybrid laminar flow control (HLFC) experiment conducted in the NASA LaRC 8 ft Transonic Pressure Tunnel on a 7 ft chord, 23 deg swept model. The methods/codes used to obtain the contours of the HLFC model surface and to define the suction requirements are outlined followed by a discussion of the model construction, suction system, instrumentation, and some example results from the wind tunnel tests. Included in the latter are the effects of Mach number, suction level, and the extent of suction. An assessment is also given of the effect of the wind tunnel environment on the suction requirements. The data show that, at or near the design Mach number, large extents of laminar flow can be achieved with suction mass flows over the first 25 percent, or less, of the chord. Top surface drag coefficients with suction extending from the near leading edge to 20 percent of the chord were approximately 40 percent lower than those obtained with no suction. The results indicate that HLFC can be designed for transonic speeds with lift and drag coefficients approaching those of LFC designs but with much smaller extents and levels of suction

Wide Field X-Ray Telescope Mission Concept Study Results

The Wide Field X-Ray Telescope (WFXT) is an astrophysics mission concept for detecting and studying extra-galactic x-ray sources, including active galactic nuclei and clusters of galaxies, in an effort to further understand cosmic evolution and structure. This Technical Memorandum details the results of a mission concept study completed by the Advanced Concepts Office at NASA Marshall Space Flight Center in 2012. The design team analyzed the mission and instrument requirements, and designed a spacecraft that enables the WFXT mission while using high heritage components. Design work included selecting components and sizing subsystems for power, avionics, guidance, navigation and control, propulsion, structures, command and data handling, communications, and thermal control

Gold nanoparticles as catalysts for low-temperature WGS reaction

OBJECTIVES: This study aimed to compare the phenotype of Rett syndrome cases with C-terminal deletions to that of cases with different MECP2 mutations and to examine the phenotypic variation within C-terminal deletions. METHODS: Cases were selected from InterRett, an international database and from the population-based Australian Rett Syndrome Database. Cases (n=832) were included if they had a pathogenic MECP2 mutation in which the nature of the amino acid change was known. Three severity scale systems were used, and individual aspects of the phenotype were also compared. RESULTS: Lower severity was associated with C-terminal deletions (n=79) compared to all other MECP2 mutations (e.g. Pineda scale C-terminals mean 15.0 (95% CI 14.0–16.0) vs 16.2 (15.9–16.5). Cases with C-terminal deletions were more likely to have a normal head circumference (odds ratio 3.22, 95% CI 1.53 – 6.79) and weight (odds ratio 2.97, 95% CI 1.25–5.76). Onset of stereotypies tended to be later (median age 2.5 years vs 2 years, p<0.001 from survival analysis), and age of learning to walk tended to be earlier (median age 1.6 years vs 2 years, p=0.002 from survival analysis). Those with C-terminal deletions occurring later in the region had lower average severity scores than those occurring earlier in the region. CONCLUSION: In terms of overall severity C-terminal deletion cases would appear to be in the middle of the range. In terms of individual aspects of phenotype growth and ability to ambulate appear to be particular strengths. By pooling data internationally this study has achieved the case numbers to provide a phenotypic profile of C-terminal deletions in Rett syndrome

Impact of diagnosis of diabetes on health-related quality of life among high risk individuals: the Diabetes Prevention Program outcomes study

Purpose The purpose of this study is to assess if diagnosis of type 2 diabetes affected health-related quality of life (HRQoL) among participants in the Diabetes Prevention Program/Diabetes Prevention Program Outcome Study and changes with treatment or diabetes duration. Methods 3,210 participants with pre-diabetes were randomized to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB). HRQoL was assessed using the SF-36 including: (1) 8 SF-36 subscales; (2) the physical component (PCS) and mental component summary (MCS) scores; and (3) the SF-6D. The sample was categorized by diabetes free versus diagnosed. For diagnosed subgroup, mean scores in the diabetes-free period, at 6 months, 2, 4 and 6 years post-diagnosis, were compared. Results PCS and SF-6D scores declined in all participants in all treatment arms (P <.001). MCS scores did not change significantly in any treatment arm regardless of diagnosis. ILS participants reported a greater decrease in PCS scores at 6 months post-diagnosis (P <.001) and a more rapid decline immediately post-diagnosis in SF-6D scores (P = .003) than the MET or PLB arms. ILS participants reported a significant decrease in the social functioning subscale at 6 months (P <.001) and two years (P <.001) post-diagnosis. Conclusions Participants reported a decline in measures of overall health state (SF-6D) and overall physical HRQoL, whether or not they were diagnosed with diabetes during the study. There was no change in overall mental HRQoL. Participants in the ILS arm with diabetes reported a more significant decline in some HRQoL measures than those in the MET and PLB arms that developed diabetes

Predictors of Serum Polychlorinated Biphenyl Concentrations in Anniston Residents

The Anniston Community Health Survey was a community-based cross-sectional study of Anniston, Alabama, residents who live in close proximity to a former PCB production facility to identify factors associated with serum PCB levels. The survey comprises 765 Anniston residents who completed a questionnaire interview and provided a blood sample for analysis in 2005–2007. Several reports based on data from the Anniston survey have been previously published, including associations between PCB exposure and diabetes and blood pressure. In this study we examine demographic, behavioral, dietary, and occupational characteristics of Anniston survey participants as predictors of serum PCB concentrations. Of the 765 participants, 54% were White and 45% were African-American; the sample was predominantly female (70%), with a mean age of 55 years. Serum PCB concentrations varied widely between participants (range for sum of 35 PCBs: 0.11–170.4 ng/g wet weight). Linear regression models with stepwise selection were employed to examine factors associated with serum PCBs. Statistically significant positive associations were observed between serum PCB concentrations and age, race, residential variables, current smoking, and local fish consumption, as was a negative association with education level. Age and race were the most influential predictors of serum PCB levels. A small age by sex interaction was noted, indicating that the increase in PCB levels with age was steeper for women than for men. Significant interaction terms indicated that the associations between PCB levels and having ever eaten locally raised livestock and local clay were much stronger among African-Americans than among White participants. In summary, demographic variables and past consumption of locally produced foods were found to be the most important predictors of PCB concentrations in residents living in the vicinity of a former PCB manufacturing facility

This advert makes me cry: Disclosure of emotional response to advertisement on Facebook

As social media is transforming how consumers interact with brands and how brand-related content is consumed, this paper aims to investigate if and how Facebook users express their emotions towards advertisements of brand share on the site. Seven hundred and three comments about the Lloyds 250th Anniversary advertisement on Facebook were analysed as positive, negative or neutral attitude towards the advert. Facebook users found the advertisement emotionally appealing and voluntarily report their emotion of love, pride and in some cases anger. The presence of an iconic image like the black horse and the cover music was found to be emotionally appealing. The background music as well aroused positive emotions and engaging. This study introduces the possibility of analysing Facebook comments on brand content to understand consumers’ emotional responses and attitudes to the brand. Managers can explore these opportunities to identify what consumers find interesting in advertisements and how best to develop their creative strategies. It also offers the opportunity to allocate resources better to engage consumers with creative advertisement. Unlike interviews or surveys, this is a pioneering study on measuring emotional responses to advertisement through users’ self-report on social media