Design for a Darwinian Brain: Part 1. Philosophy and Neuroscience

Physical symbol systems are needed for open-ended cognition. A good way to understand physical symbol systems is by comparison of thought to chemistry. Both have systematicity, productivity and compositionality. The state of the art in cognitive architectures for open-ended cognition is critically assessed. I conclude that a cognitive architecture that evolves symbol structures in the brain is a promising candidate to explain open-ended cognition. Part 2 of the paper presents such a cognitive architecture.Comment: Darwinian Neurodynamics. Submitted as a two part paper to Living Machines 2013 Natural History Museum, Londo

A Phase I/II trial comparing autologous dendritic cell vaccine pulsed either with personalized peptides (PEP-DC) or with tumor lysate (OC-DC) in patients with advanced high-grade ovarian serous carcinoma.

Most ovarian cancer patients are diagnosed at a late stage with 85% of them relapsing after surgery and standard chemotherapy; for this reason, new treatments are urgently needed. Ovarian cancer has become a candidate for immunotherapy by reason of their expression of shared tumor-associated antigens (TAAs) and private mutated neoantigens (NeoAgs) and the recognition of the tumor by the immune system. Additionally, the presence of intraepithelial tumor infiltrating lymphocytes (TILs) is associated with improved progression-free and overall survival of patients with ovarian cancer. The aim of active immunotherapy, including vaccination, is to generate a new anti-tumor response and amplify an existing immune response. Recently developed NeoAgs-based cancer vaccines have the advantage of being more tumor specific, reducing the potential for immunological tolerance, and inducing robust immunogenicity. We propose a randomized phase I/II study in patients with advanced ovarian cancer to compare the immunogenicity and to assess safety and feasibility of two personalized DC vaccines. After standard of care surgery and chemotherapy, patients will receive either a novel vaccine consisting of autologous DCs pulsed with up to ten peptides (PEP-DC), selected using an agnostic, yet personalized, epitope discovery algorithm, or a sequential combination of a DC vaccine loaded with autologous oxidized tumor lysate (OC-DC) prior to an equivalent PEP-DC vaccine. All vaccines will be administered in combination with low-dose cyclophosphamide. This study is the first attempt to compare the two approaches and to use NeoAgs-based vaccines in ovarian cancer in the adjuvant setting. The proposed treatment takes advantage of the beneficial effects of pre-treatment with OC-DC prior to PEP-DC vaccination, prompting immune response induction against a wide range of patient-specific antigens, and amplification of pre-existing NeoAgs-specific T cell clones. Trial registration This trial is already approved by Swissmedic (Ref.: 2019TpP1004) and will be registered at http://www.clinicaltrials.gov before enrollment opens

The long-term survival chances of young massive star clusters

We review the long-term survival chances of young massive star clusters (YMCs), hallmarks of intense starburst episodes often associated with violent galaxy interactions. We address the key question as to whether at least some of these YMCs can be considered proto-globular clusters (GCs), in which case these would be expected to evolve into counterparts of the ubiquitous old GCs believed to be among the oldest galactic building blocks. In the absence of significant external perturbations, the key factor determining a cluster's long-term survival chances is the shape of its stellar initial mass function (IMF). It is, however, not straightforward to assess the IMF shape in unresolved extragalactic YMCs. We discuss in detail the promise of using high-resolution spectroscopy to make progress towards this goal, as well as the numerous pitfalls associated with this approach. We also discuss the latest progress in worldwide efforts to better understand the evolution of entire cluster systems, the disruption processes they are affected by, and whether we can use recently gained insights to determine the nature of at least some of the YMCs observed in extragalactic starbursts as proto-GCs. We conclude that there is an increasing body of evidence that GC formation appears to be continuing until today; their long-term evolution crucially depends on their environmental conditions, however.Comment: invited refereed review article; ChJA&A, in press; 33 pages LaTeX (2 postscript figures); requires chjaa.cls style fil

Cluster Density and the IMF

Observed variations in the IMF are reviewed with an emphasis on environmental density. The remote field IMF studied in the LMC by several authors is clearly steeper than most cluster IMFs, which have slopes close to the Salpeter value. Local field regions of star formation, like Taurus, may have relatively steep IMFs too. Very dense and massive clusters, like super star clusters, could have flatter IMFs, or inner-truncated IMFs. We propose that these variations are the result of three distinct processes during star formation that affect the mass function in different ways depending on mass range. At solar to intermediate stellar masses, gas processes involving thermal pressure and supersonic turbulence determine the basic scale for stellar mass, starting with the observed pre-stellar condensations, and they define the mass function from several tenths to several solar masses. Brown dwarfs require extraordinarily high pressures for fragmentation from the gas, and presumably form inside the pre-stellar condensations during mutual collisions, secondary fragmentations, or in disks. High mass stars form in excess of the numbers expected from pure turbulent fragmentation as pre-stellar condensations coalesce and accrete with an enhanced gravitational cross section. Variations in the interaction rate, interaction strength, and accretion rate among the primary fragments formed by turbulence lead to variations in the relative proportions of brown dwarfs, solar to intermediate mass stars, and high mass stars.Comment: 14 pages, 3 figures, to be published in ``IMF@50: A Fest-Colloquium in honor of Edwin E. Salpeter,'' held at Abbazia di Spineto, Siena, Italy, May 16-20, 2004. Kluwer Academic Publishers; edited by E. Corbelli, F. Palla, and H. Zinnecke

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

Gender differences in the impact of daily sadness on 24-h heart rate variability

Reduced heart rate variability (HRV) is proposed to mediate the relation between depressive symptoms and cardiovascular health problems. Yet, several studies have found that in women depression is associated with higher HRV levels, whereas in men depression is associated with lower HRV levels. So far, these studies have only examined gender differences in HRV levels using a single assessment. This study aimed to test the interactive effects of gender and sadness on ambulatory-assessed HRV levels. A sample of 60 (41 women) employees participated in an ambulatory study. HRV levels (mean of successive differences; MSD) were continuously measured for 24 h. During the daytime, hourly assessments of sadness and other mood states were taken, while depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale (CES-D). Gender differences were observed when examining the impact of average daily sadness on MSD. In women, but not in men, the total amount of sadness experienced during the day was associated with higher circadian MSD levels. These findings suggest that researchers need to take gender differences into account when examining the relation between sadness, HRV, and cardiovascular problems.FSW - Self-regulation models for health behavior and psychopathology - ou