Search

In this paper I develop a sketch of an overall theology that dispenses with “alternative-possibilities” freedom in favor of “actual-sequence” freedom. I hold that acting freely does not require freedom to do otherwise, and that acting freely is the freedom component of moral responsibility. Employing this analytical apparatus, I show how we can offer various important elements of a theology that employs only the notion of acting freely. I distinguish my approach from the important development of Open Theism by William Hasker. My view about God’s foreknowledge is in-between comprehensive foreknowledge and no foreknowledge (Open Theism).

In a recent article in this journal, “Destinism,” Andrew Bailey presents a puzzle (in different versions) for “Destinism,” the view that the only things we can do are those we in fact do. The puzzle is intriguing and important in part because it challenges a doctrine (Destinism) that many philosophers think could be true compatibly with our being morally responsible. Destinism is at least a viable view. Bailey’s puzzle derives from very plausible assumptions, but I argue that these assumptions are not as plausible as they appear. Interpreted in a way that renders one of them acceptable makes another problematic. There is no one interpretation on which the puzzling arguments are uncontrovertibly sound.

The coordination of transcription through enhancers and promoters is a fundamental process that has a central role in development and disease 1–3. Convergent transcription, i.e., the collision of sense and antisense transcription, is ubiquitous in mammalian genomes 4–8 and believed to diminish RNA expression 9,10. Recently, antisense transcription downstream of promoters was found to be surprisingly prevalent 11–13. However, functional characteristics of promoters with convergent transcription are unknown. Here, we show that convergent transcription marks an unexpectedly cooperative promoter constellation we call super-promoters. By assessing transcriptional dynamic systems, we identified strongly cooperative constituent promoters that are connected through a distinct chromatin structure. Within these super-promoter constellations transcription factors can regulate both constituting promoters by binding to only one of them. Super-promoters comprise about a fourth of all active transcript starts and initiate 5’-overlapping antisense RNAs, an RNA class previously believed to be rare 4. Visualization of nascent RNA molecules provides evidence for convergent co-transcription at these loci. Our results demonstrate that super-promoters substantially expand the cis-regulatory repertoire and reveal limitations of the standing model of transcription interference. Together, our study revises the promoter architecture of many genes and calls for adjusting the promoter concept.

The emergence of cloud computing, big data analytics, and machine learning has catalysed the use of remote sensing technologies to enable more timely land management of sustainability indicators such as ground cover and grassland biomass, given the uncertainty of future climate and drought conditions. Here, we examine the potential of “regenerative agriculture”, as an adaptive grazing management strategy to minimise bare ground exposure while maximising pasture biomass productivity. High-intensity sheep grazing treatments were conducted in small fields (less than 1 hectare) for short durations (typically less than 1 day). Paddocks were subsequently spelled to allow pasture biomass recovery (treatments comprising 3, 6, 9, 12, and 15 months) with each compared with control treatments with lighter stocking rates for longer periods (2,000 DSE). Pastures were composed of wallaby grass (Austrodanthonia species), kangaroo grass (Themeda triandra), Phalaris (Phalaris aquatica, and cocksfoot (Dactylis glomerata) were destructively sampled to estimate total standing dry matter (TSDM), standing green biomass, standing dry biomass and trampled biomass. We then invoked a machine learning model using Sentinel-2 imagery to quantify TSDM, standing green biomass and standing dry biomass. Faced with La Nina conditions, regenerative grazing did not significantly impact pasture productivity, with all treatments showing similar TSDM and green biomass. However, regenerative treatments significantly impacted litter fall and trampled material, with the high intensity grazing treatments causing more dry matter trampling, increasing litter, enhancing decomposition rates and surface organic matter. Pasture digestibility was greatest for treatments with minimal spelling (3 months), whereas both standing senescent and trampled material were significantly greater for the treatment with 15-month spell periods. Estimates of TSDM using machine learning with Sentinel-2 imagery underestimated TSDM in treatment plots but explained spatiotemporal variability associated within and across treatments. The root mean square error between the measured and modelled TSDM was 903 kg DM/ha, which was less than the variability measured in the field. We conclude that regenerative grazing with short recovery periods (3-6 months) are most conducive to increasing pasture production under high rainfall conditions, and we speculate that high intensity grazing is likely to positively impact on soil organic carbon through increased litterfall and trampling. Our study paves the way forward for using machine learning with satellite imagery to quantify pasture biomass at small scales, enabling management of pastures from afar.

I offer an overview of the book, Death, Immortality, and Meaning in Life, summarizing the main issues, arguments, and conclusions (Fischer 2020). I also present some new ideas and further developments of the material in the book. A big part of this essay is drawing connections between the specific issues treated in the book and those in other areas of philosophy, and in particular, the theory of agency and moral responsibility. I highlight some striking similarities of both structure and content between the death/meaning in life literature and the free will/moral responsibility literature.

In my reply to the thoughtful comments of Timmerman and Gorman, I take up, and further explore, some main questions, including: Can a horribly immoral person (a moral monster) lead a meaningful life? Similarly, can a significantly deluded person lead a meaningful life? What role do judgments of meaningfulness play in our normative framework? How can we understand the debate between those who would embrace the possibility of immortality and those who would reject it? What is the role of narrativity in evaluating meaning in human lives, and how would this concept apply to immortal lives? If death can be a bad thing for the deceased, should we fear death (the status of being dead)?

Przekład na podstawie: „Responsiveness and Moral Responsibility”, w: Responsibility, Character, and the Emotions: New Essays in Moral Psychology, red. Ferdinand Schoeman (Cambridge: Cambridge University Press, 1987), 81–106; przedruk w: John Martin Fischer, My Way: Essays on Moral Responsibility (Oxford: Cambridge University Press, 2006), 63–83. Przekład za zgodą Autora. Autor przedstawia model odpowiedzialności moralnej oparty na faktycznej sekwencji i pojęciu zdolności reagowania na racje, a następnie przeprowadza analogię między tym modelem a opracowanym przez Roberta Nozicka modelem wiedzy opartej na faktycznej sekwencji, oraz wprowadza pojęcie semikompatybilizmu.

Przekład na podstawie: “The Frankfurt Cases: The Moral of the Stories”, Philosophical Review 119 (2010): 315–336. Przekład za zgodą Autora Autor argumentuje, że morał przykładów frankfurtowskich jest następujący: jeśli determinizm przyczynowy wyklucza odpowiedzialność moralną, to nie na mocy eliminacji alternatywnych możliwości, a następnie odpowiada na najważniejsze wyzwanie dla tej tezy, mianowicie argument nazywany „obroną przez dylemat”.

Language processing is influenced by sensorimotor experiences. Here, we review behavioral evidence for embodied and grounded influences in language processing across six linguistic levels of granularity. We examine (a) sub-word features, discussing grounded influences on iconicity (systematic associations between word form and meaning); (b) words, discussing boundary conditions and generalizations for the simulation of color, sensory modality, and spatial position; (c) sentences, discussing boundary conditions and applications of action direction simulation; (d) texts, discussing how the teaching of simulation can improve comprehension in beginning readers; (e) conversations, discussing how multi-modal cues improve turn taking and alignment; and (f) text corpora, discussing how distributional semantic models can reveal how grounded and embodied knowledge is encoded in texts. These approaches are converging on a convincing account of the psychology of language, but at the same time, there are important criticisms of the embodied approach and of specific experimental paradigms. The surest way forward requires the adoption of a wide array of scientific methods. By providing complimentary evidence, a combination of multiple methods on various levels of granularity can help us gain a more complete understanding of the role of embodiment and grounding in language processing.

The aim of the study presented in this paper was to first evaluate a new control logic together with hardware changes done to the DLR bicycle simulator and identify in which areas it is possible to fine tune the simulator so that it allows for a more realistic behavior. For this purpose, two different versions of the simulator will be compared based on objective criteria first in a simulator study and then to data of an equipped research bicycle.

Recurrently mutated in lymphoid neoplasms, the transcription factor RFX7 is emerging as a tumor suppressor. Previous reports suggested that RFX7 may also have a role in neurological and metabolic disorders. We recently reported that RFX7 responds to p53 signaling and cellular stress. Furthermore, we found RFX7 target genes to be dysregulated in numerous cancer types also beyond the hematological system. However, our understanding of RFX7’s target gene network and its role in health and disease remains limited. Here, we generated RFX7 knock-out cells and employed a multi-omics approach integrating transcriptome, cistrome, and proteome data to obtain a more comprehensive picture of RFX7 targets. We identify novel target genes linked to RFX7’s tumor suppressor function and underscoring its potential role in neurological disorders. Importantly, our data reveal RFX7 as a mechanistic link that enables the activation of these genes in response to p53 signaling.

Cellular senescence is a stable cell cycle arrest that normal cells undergo after a finite number of divisions, in response to a variety of intrinsic and extrinsic stimuli. Although senescence is largely established and maintained by the p53/p21WAF1/CIP1 and pRB/p16INK4A tumour suppressor pathways, the downstream targets responsible for the stability of the growth arrest are not known. We have employed a stable senescence bypass assay in conditionally immortalised human breast fibroblasts (CL3EcoR) to investigate the role of the DREAM complex and its associated components in senescence. DREAM is a multi-subunit complex comprised of the MuvB core, containing LIN9, LIN37, LIN52, LIN54, and RBBP4, that when bound to p130, an RB1 like protein, and E2F4 inhibits cell cycle-dependent gene expression thereby arresting cell division. Phosphorylation of LIN52 at Serine 28 is required for DREAM assembly. Re-entry into the cell cycle upon phosphorylation of p130 leads to disruption of the DREAM complex and the MuvB core, associating initially to B-MYB and later to FOXM1 to form MMB and MMB-FOXM1 complexes respectively. Here we report that simultaneous expression of MMB-FOXM1 complex components efficiently bypasses senescence with LIN52, B-MYB, and FOXM1 as the crucial components. Moreover, bypass of senescence requires non-phosphorylated LIN52 that disrupts the DREAM complex, thereby indicating a central role for assembly of the DREAM complex in senescence.

Bridging the Gap- Workshop series 2020-21 This is the full report and discussions in the consensus building workshops and highlights of the thematic synthesis.

Differential Attainment Healthcare professionals are among the most respected, valued members in any society- and also the most regulated. It attracts some of the most talented, innovative and resilient individuals who are keen to do good. Respect, job satisfaction and autonomy are fundamental to the experience of any professional, and often valued above financial or material reward. Doctors are no different. Education and training of the healthcare workforce is a lengthy and resource intense process. No nation-state can be truly self-sufficient. Hence workforce migration is a reality where various pull and push factors lead to professionals moving across countries and continents, in the service of populations. Society is divided along many lines and steeped with structural inequalities. Many of these are the result of thousands of years of history, legacy and societal wrongs. Healthcare services and professionals reflect similar patterns of the 'big society'. The phenomenon of differential attainment (DA), which is the subject of this report is simply a manifestation of such structural inequalities. DA or differential outcomes for doctors due to their age, race, gender, sexual orientation, ethnicity, disability, socio-economic deprivation or influenced by migrant status - rather than motivation, ability, effort or enterprise. DA is fundamentally unfair. Those affected by DA are either unaware or unable to counteract the influence on their careers. DA leads to demoralisation, disengagement and poor outcomes for professionals and their patients. It takes its toll not only on careers but on lives and livelihoods. DA leads to a huge under-utlisation of human resources- a true waste of talent and enterprise. This report- BTG21 focuses on DA in the medical profession exploring the career cycle through the themes of recruitment, assessments, career progression, research & academia, leadership roles, awards and professionalism. BTG21 is people-centred and in tackling inequalities offers solutions on career fulfillment and wellbeing- by an ideological shift of hearts and minds. Thematic Synthesis BTG21 summary report is the culmination of a thematic synthesis of evidence covering the full spectrum of medical careers. It presents lived experiences (collected through mixed method approaches) capturing patterns in peoples experiences through an online survey, and in-depth qualitative interviews with a purposive sample of professionals from across the career cycle, range of ethnic heritage, medical specialism and country of origin. Followed by consensus developed through workshops by a triumvirate of experts, stakeholders and grassroots professionals. There are 5 primary causes of DA- bias, social class & deprivation, immigration status, geographical and individual factors and impacts every stage of medical professional careers. The thematic synthesis reviews are published in the Sushruta Journal of Health Policy. Recommendations The Workshop discussions, recommendations (the 10-point plan) include policy enablers, immediate actions and research questions in the following areas; Tackling bias Embracing diversity & inclusion Celebrating the contribution of migrants Leveling the playing field Inclusive leadership & accountability Removing structural barriers Review-Reform-Rethink assessments Redefining professionalism Disaggregation-intersectionality-benchmarking of data Support-flexibility & Wellbeing

This paper deals with the historical development of the noise emission of cars, trucks and their petrol and diesel engines; it focus on the European Union and the time period between 1910 and 2020. Combustion engines were and are important noise sources of road vehicles. Until around 1970 engine noise levels were increased strongly by higher speeds, by higher cylinder pressures and especially for truck engines by the introduction of the diesel combustion process. The noise emission was mainly caused by the drive train until the 1960ies for cars and until the 1970ies for trucks. Since then the development of acoustically more advantageous engines was forced by noise regulations and simultaneously enabled by technical advancements. As a consequence of the acoustical optimization of the engines the tire/road noise became dominant. Despite of the technical advancements the road noise stress of the population is still much too high. Therefor the necessary short-term reduction of noise stress has to be realized by regulatory measures.

This paper describes a novel method to select the optimal member sizes and connection types for steel frame structures to minimize total installed cost. The proposed dimension increasing search (DIS) method addresses geometric constraints associated with connection, safety, and serviceability constraints. Solving this optimization problem requires addressing a non-convex objective function of total installed cost, a large number of constraints, the time-consuming structural analysis for evaluation of the constraints, and intractability resulting from high-dimensional variables. The DIS method involves initial grouping of design variables to reduce the search dimension from the original dimension. Random search coupled with forward checking and branch-and-bound techniques are then employed to optimize the configuration of the steel frame. This approach eliminates designs that are more expensive or do not satisfy geometric constraints without performing structural analysis. The variable groups are then split into subgroups to increase the search dimension, and the increased dimensional design variables are optimized until the original search dimension is achieved. We benchmarked the DIS method against leading methods using three numerical examples with increasing problem scales. The DIS method was more computationally efficient compared to other leading methods by an order of magnitude, and the solutions found by the method have a 9% lower total installed cost on average. The DIS method also showed scalability; the computational time increased only slightly as the problem scale increased. The scalability of the DIS method demonstrates the potential for its successful industrial application to large-scale building projects.

The Frankfurt-style Counterexamples (FSCs) to the Principle of Alternative Possibilities (PAP) have been controversial. I sketch some of the major moves in the debates surrounding the FSCs, and I s...