The impact of spatial and verbal working memory load on semantic relatedness judgements

Studies using a relatedness judgement task have found differences between prime17 target word pairs that vary in the degree of semantic relatedness (Balota & Paul, 1996; Kuperberg et al., 2008). However, the influence of working memory load on semantic processing in this task and the role of the type of working memory task have not yet been investigated. The present study therefore investigated for the first time the effect of working memory load (low vs. high) and working memory type (verbal vs. spatial) on semantic relatedness judgements. Semantically strongly related (e.g. hip – KNEE), weakly related (e.g. muscle – KNEE) and unrelated (e.g. office – KNEE) Polish word pairs were presented in an experiment involving a dual working memory and semantic relatedness task. The data revealed that, relative to semantically unrelated word pairs, responses were faster for strongly related pairs but slower for weakly related pairs. Importantly, the verbal working memory task decreased facilitation for strongly related pairs and increased inhibition for weakly related pairs relative to the spatial working memory task. Furthermore, working memory load impacted only weakly related pairs in the verbal but not in the spatial working memory task. These results show that working memory type and load influence semantic relatedness judgements, but the direction and size of the impact depend on the strength of semantic relation

Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel

PURPOSE This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS Peripheral blood mononuclear cells were isolated before and 30~days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. RESULTS Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0~months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0~months (p = 0.011), respectively. CONCLUSIONS Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC

PD1-CD28 Fusion Protein Enables CD4+ T Cell Help for Adoptive T Cell Therapy in Models of Pancreatic Cancer and Non-hodgkin Lymphoma

Background: Interaction of the programmed death receptor 1 (PD-1) and its ligand, PD-L1, suppresses T cell activity and permits tumors to evade T cell-mediated immune surveillance. We have recently demonstrated that antigen-specific CD8+ T cells transduced with a PD1-CD28 fusion protein are protected from D-1-mediated inhibition. We have now investigated the potential of PD1-CD28 fusion protein-transduced CD4+ T cells alone or in combination with CD8+ T cells for immunotherapy of pancreatic cancer and non-Hodgkin lymphoma. Methods: OVA-specific CD4+ and CD8+ were retrovirally transduced with the PD1-CD28 fusion protein. Cytokine release, proliferation, cytotoxic activity, and phenotype of transduced T cells were assessed in the context of Panc02-OVA (murine pancreatic cancer model) and E.G7-PD-L1 (murine T cell lymphoma model) cells. Results: Stimulation of PD1-CD28 fusion protein-transduced CD4+ T cells with anti-CD3 and recombinant PD-L1 induced specific T cell activation, as measured by IFN-y release and T cell proliferation. Coculture with Panc02-OVA or E.G7-PD-L1 tumor cells also led to specific activation of CD4+ T cells. Cytokine release and T cell proliferation was most effective when tumor cells simultaneously encountered genetically engineered CD4+ and CD8+ T cells. Synergy between both cell populations was also observed for specific tumor cell lysis. T cell cytotoxicity was mediated via granzyme B release and mediated enhanced tumor control in vivo. Transduced CD4+ and CD8+ T cells in co-culture with tumor cells developed a predominant central memory phenotype over time. Different ratios of CD4+ and CD8+ transduced T cells led to a significant increase of IFN-y and IL-2 secretion positively correlating with CD4+ T cell numbers used. Mechanistically, IL-2 and MHC-I were central to the synergistic activity of CD4+ and CD8+ T cells, since neutralization of IL-2 prevented the crosstalk between these cell populations. Conclusion: PD1-CD28 fusion protein-transduced CD4+ T cells significantly improved anti-tumoral effect of fusion protein-transduced CD8+ T cells. Thus, our results indicate that PD1-CD28 fusion protein-transduced CD4+ T cells have the potential to overcome the PD-1-PD-L1 immunosuppressive axis in pancreatic cancer and non-Hodgkin lymphoma

Field evaluation of controlled traffic farming in central Europe using commercially available machinery

The progressive increase in the size and weight of farm machinery causes concerns due to the increased risk of soil compaction that arises from non-organized vehicle traffic. Controlled traffic farming (CTF) offers an effective means to manage compaction by confining all load-bearing wheels to the least possible area of permanent traffic lanes. Although CTF is relatively well-established in Australia and in some countries in Northern Europe, its benefits and suitability for Central European conditions have not been demonstrated. A long-term experimental site was established in 2010 in Nitra, Slovakia, using a 6 m 'OutTrac-CTF' system with shallow non-inversion tillage practices. The 16 ha experimental field of loam soil is representative of land used for arable cropping in Central Europe. Four traffic intensities (non-trafficked, one traffic event per year with a single pass, multiple passes with permanent traffic lanes, and random traffic) were evaluated using two traffic systems: controlled (CTF) and non-controlled traffic farming (referred to as random traffic farming or RTF). This article reports the findings derived from the first four years of the project and focuses on the effects of traffic systems on yields observed in cereal crops (winter wheat, spring barley, and maize) grown at the site in a rotation cycle. Significant differences (p < 0.1) in yield are reported due to the heterogeneity of the field and the seasonal effect of weather. The results of this investigation suggest that CTF systems have potential to increase production sustainably in arable farming systems in Central Europe. Well-designed CTF systems using commercially available machinery allow for reductions in the area affected by traffic of up to 50% compared with random, non-organized traffic systems. Results also show that in years when soil moisture was not limiting, the yield penalty from a single (annual) machine pass was relatively small (~5%). However, in dry years, compaction caused by multiple machinery passes may lead to yield losses of up to 33%. When considering the ratio of non-trafficked to trafficked area within the different CTF systems evaluated in this study, yield improvements of up to 0.5 t ha-1 for cereals are possible when converting from RTF to CTF. Given the assumptions made in the analyses, such yield increases translate into increased revenues of up to 117 USD ha-1 (1 Euro= 1.1 USD). For Central European farming systems, the main benefit of CTF appears to be improved efficiency and enhanced agronomic stability, especially in dry seasons, where the significant yield penalty from machinery passes is likely

Design of an optimized nested-mirror neutron reflector for a NNBAR experiment

The NNBAR experiment for the European Spallation Source will search for free neutrons converting to antineutrons with an expected sensitivity improvement of three orders of magnitude compared to the last such search. This paper describes both the simulations of a key component for the experiment, the neutron optical reflector and the expected gains in sensitivity

The HIBEAM program: search for neutron oscillations at the ESS

With the construction of the European Spallation Source, a remarkable opportunity has emerged to conduct high sensitivity searches for neutron oscillations, including a first search for thirty years for free neutrons converting to antineutrons. Furthermore, searches can be made for transitions of neutrons and antineutrons to sterile neutron states. The HIBEAM program provides an increase in sensitivity of an order of magnitude compared to previous work. The HIBEAM program corresponds to baryon number violation by one and two units. The observation of a process satisfying a Sakharov condition addresses the open question of the origin of the matter-antimatter asymmetry in the Universe. Sterile neutron states would belong to a `dark' sector of particles which may explain dark matter. As electrically neutral, meta-stable objects that can be copiously produced and studied, neutrons represent an attractive portal to a `dark' sector. This paper describes the capability, design, infrastructure, and potential of the HIBEAM program. This includes a dedicated beamline, neutron optical system, magnetic shielding and control, and detectors for neutrons and antineutrons.Comment: 41 pages, 12 figure

Development of a High Intensity Neutron Source at the European Spallation Source: The HighNESS project

The European Spallation Source (ESS), presently under construction in Lund, Sweden, is a multidisciplinary international laboratory that will operate the world's most powerful pulsed neutron source. Supported by a 3M Euro Research and Innovation Action within the EU Horizon 2020 program, a design study (HighNESS) is now underway to develop a second neutron source below the spallation target. Compared to the first source, located above the spallation target and designed for high cold and thermal brightness, the new source will provide higher intensity, and a shift to longer wavelengths in the spectral regions of cold (2 /- 20 {\AA}), very cold (VCN, 10 /- 120 {\AA}), and ultra cold (UCN, > 500 {\AA}) neutrons. The core of the second source will consist of a large liquid deuterium moderator to deliver a high flux of cold neutrons and to serve secondary VCN and UCN sources, for which different options are under study. The features of these new sources will boost several areas of condensed matter research and will provide unique opportunities in fundamental physics. Part of the HighNESS project is also dedicated to the development of future instruments that will make use of the new source and will complement the initial suite of instruments in construction at ESS. The HighNESS project started in October 2020. In this paper, the ongoing developments and the results obtained in the first year are described.Comment: 10 pages, 10 figures, 14th International Topical Meeting on Nuclear Applications of Accelerators, November 30 to December 4, 2021, Washington, D

Quality of life and cost-effectiveness of interferon-alpha in malignant melanoma: results from randomised trial

A definitive conclusion regarding the value of low-dose extended duration adjuvant interferon-alpha therapy in the treatment of malignant melanoma is only possible once data on health-related quality of life (HRQoL) and costs have been considered. This trial randomised 674 patients to interferon alpha-2a (3 megaunits three times per week for 2 years or until recurrence) or placebo. Health-related quality of life (QoL) was to be assessed up to 60 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Data for the economic analysis, including cost information and the EQ-5D were also collected. Patients in the observation (OBS) group had significantly better mean follow-up quality of on five dimensions of the EORTC QLQ-C30 functional scales: role functioning (P=0.033), emotional functioning (P=0.003), cognitive functioning (P=0.001), social functioning (P=0.003) and global health status (P=0.001). Patients in the OBS group had significantly better mean follow-up symptom scores on seven dimensions of the EORTC QLQ-C30 V1 symptom scales. Economic data showed that costs were £3066 higher in the interferon group and produces an incremental cost per quality-adjusted life year of £41 432 at 5 years. The results show that interferon has significant effects on QoL and symptomatology and is unlikely to be cost-effective in this patient group in the UK

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio