Belief, reasons, and irrationality

In this thesis, we explore the question: What is a belief? We do so by considering the folk psychological concept of belief and attempting to unearth some constitutive features of it. We argue that, according to this concept, there is a significant relationship between belief and reasons: one which reveals that beliefs aim at truth, as Bernard Williams (1973) once famously put it. We argue for a particular interpretation of this claim, according to which it is to be understood as follows: (R): It is constitutive of belief that if it is consciously regulated, it is so-regulated solely for truth; and (C): It is constitutive of belief that it is correct if and only if its contents are true. We maintain that (C) explains why it is that (R) is true. So, belief is at base a normative concept: the question as to why one holds a particular belief can always be raised. We then explore two irrational phenomena – self-deception and delusion – and further unravel what (R) and (C) involve, as well as shedding some light on the phenomena themselves. We argue for a position we call doxastic minimalism about self-deception, according to which, in the paradigm case, the self-deceiver holds neither their undesired belief that p nor their desired belief that ~p. This is because they do not have attitudes to these contents that meet conditions (R) and (C). Similarly, we argue that although cases of delusion vary significantly, in some extreme cases, the subject does not seem to relate to the content of their delusion in a manner that meets (R) and (C), and hence ought not to be attributed a belief in such contents

The future of biomolecular simulation in the pharmaceutical industry: what we can learn from aerodynamics modelling and weather prediction. Part 1. understanding the physical and computational complexity of in silico drug design

The predictive power of simulation has become embedded in the infrastructure of modern economies. Computer-aided design is ubiquitous throughout industry. In aeronautical engineering, built infrastructure and materials manufacturing, simulations are routinely used to compute the performance of potential designs before construction. The ability to predict the behaviour of products is a driver of innovation by reducing the cost barrier to new designs, but also because radically novel ideas can be piloted with relatively little risk. Accurate weather forecasting is essential to guide domestic and military flight paths, and therefore the underpinning simulations are critical enough to have implications for national security. However, in the pharmaceutical and biotechnological industries, the application of computer simulations remains limited by the capabilities of the technology with respect to the complexity of molecular biology and human physiology. Over the last 30 years, molecular-modelling tools have gradually gained a degree of acceptance in the pharmaceutical industry. Drug discovery has begun to benefit from physics-based simulations. While such simulations have great potential for improved molecular design, much scepticism remains about their value. The motivations for such reservations in industry and areas where simulations show promise for efficiency gains in preclinical research are discussed. In this, the first of two complementary papers, the scientific and technical progress that needs to be made to improve the predictive power of biomolecular simulations, and how this might be achieved, is firstly discussed (Part 1). In Part 2, the status of computer simulations in pharma is contrasted with aerodynamics modelling and weather forecasting, and comments are made on the cultural changes needed for equivalent computational technologies to become integrated into life-science industries

Emissions from village cookstoves in Haryana, India, and their potential impacts on air quality

Air quality in rural India is impacted by residential cooking and heating with biomass fuels. In this study, emissions of CO, CO2, and 76 volatile organic compounds (VOCs) and fine particulate matter (PM2.5) were quantified to better understand the relationship between cook fire emissions and ambient ozone and secondary organic aerosol (SOA) formation. Cooking was carried out by a local cook, and traditional dishes were prepared on locally built chulha or angithi cookstoves using brushwood or dung fuels. Cook fire emissions were collected throughout the cooking event in a Kynar bag (VOCs) and on polytetrafluoroethylene (PTFE) filters (PM2.5). Gas samples were transferred from a Kynar bag to previously evacuated stainless-steel canisters and analyzed using gas chromatography coupled to flame ionization, electron capture, and mass spectrometry detectors. VOC emission factors were calculated from the measured mixing ratios using the carbon-balance method, which assumes that all carbon in the fuel is converted to CO2, CO, VOCs, and PM2.5 when the fuel is burned. Filter samples were weighed to calculate PM2.5 emission factors. Dung fuels and angithi cookstoves resulted in significantly higher emissions of most VOCs (p < 0.05). Utilizing dung-angithi cook fires resulted in twice as much of the measured VOCs compared to dung-chulha and 4 times as much as brushwood-chulha, with 84.0, 43.2, and 17.2g measured VOCkgg fuel carbon, respectively. This matches expectations, as the use of dung fuels and angithi cookstoves results in lower modified combustion efficiencies compared to brushwood fuels and chulha cookstoves. Alkynes and benzene were exceptions and had significantly higher emissions when cooking using a chulha as opposed to an angithi with dung fuel (for example, benzene emission factors were 3.18gkgg fuel carbon for dung-chulha and 2.38gkgg fuel carbon for dung-angithi). This study estimated that 3 times as much SOA and ozone in the maximum incremental reactivity (MIR) regime may be produced from dung-chulha as opposed to brushwood-chulha cook fires. Aromatic compounds dominated as SOA precursors from all types of cook fires, but benzene was responsible for the majority of SOA formation potential from all chulha cook fire VOCs, while substituted aromatics were more important for dung-angithi. Future studies should investigate benzene exposures from different stove and fuel combinations and model SOA formation from cook fire VOCs to verify public health and air quality impacts from cook fires

Compiling SHIM

Embedded systems demand concurrency for supporting simultaneous actions in their environment and parallel hardware. Although most concurrent programming formalisms are prone to races and non-determinism, some, such as our SHIM (software/hardware integration medium) language, avoid them by design. In particular, the behavior of SHIM programs is scheduling-independent, meaning the I/O behavior of a program is independent of scheduling policies, including the relative execution rates of concurrent processes. The SHIM project demonstrates how a scheduling-independent language simplifies the design, optimization, and verification of concurrent systems. Through examples and discussion, we describe the SHIM language and code generation techniques for both shared-memory and message-passing architectures, along with some verification algorithms

Molecular composition of particulate matter emissions from dung and brushwood burning household cookstoves in Haryana, India

Emissions of airborne particles from biomass burning are a significant source of black carbon (BC) and brown carbon (BrC) in rural areas of developing countries where biomass is the predominant energy source for cooking and heating. This study explores the molecular composition of organic aerosols from household cooking emissions with a focus on identifying fuel-specific compounds and BrC chromophores. Traditional meals were prepared by a local cook with dung and brushwood-fueled cookstoves in a village in Palwal district, Haryana, India. Cooking was done in a village kitchen while controlling for variables including stove type, fuel moisture, and meal. Fine particulate matter (PM2.5) emissions were collected on filters, and then analyzed via nanospray desorption electrospray ionization-high-resolution mass spectrometry (nano-DESI-HRMS) and high-performance liquid chromatography-photodiode array-high-resolution mass spectrometry (HPLC-PDA-HRMS) techniques. The nano-DESI-HRMS analysis provided an inventory of numerous compounds present in the particle phase. Although several compounds observed in this study have been previously characterized using gas chromatography methods a majority of the species in the nano-DESI spectra were newly observed biomass burning compounds. Both the stove (chulha or angithi) and the fuel (brushwood or dung) affected the composition of organic aerosols. The geometric mean of the PM2.5 emission factor and the observed molecular complexity increased in the following order: brushwood-chulha (7.3±1.8 g kg-1 dry fuel, 93 compounds), dung-chulha (21.1±4.2 g kg-1 dry fuel, 212 compounds), and dung-angithi (29.8±11.5 g kg-1 dry fuel, 262 compounds). The mass-normalized absorption coefficient (MACbulk) for the organic-solvent extractable material for brushwood PM2.5 was 3.7±1.5 and 1.9±0.8m2 g-1 at 360 and 405 nm, respectively, which was approximately a factor of two higher than that for dung PM2.5. The HPLC-PDA-HRMS analysis showed that, regardless of fuel type, the main chromophores were CxHyOz lignin fragments. The main chromophores accounting for the higher MACbulk values of brushwood PM2.5 were C8H10O3 (tentatively assigned to syringol), nitrophenols C8H9NO4, and C10H10O3 (tentatively assigned to methoxycinnamic acid)

Factors contributing to high performance of sows in free farrowing systems

\ua9 The Author(s) 2024. Background: Pressure to abolish farrowing crates is increasing, and producers are faced with decisions about which alternative system to adopt. For sow welfare, well designed free farrowing systems without close confinement are considered optimal but producers have concerns about increased piglet mortality, particularly crushing by the sow. Reporting accurate performance figures from commercial farms newly operating such systems could inform the transition process. This study investigated performance on three commercial farms operating four different zero-confinement systems, three of which were newly installed. A total of 3212 litters from 2920 sows were followed from farrowing to weaning over a three-year period with key performance indicators (KPIs) recorded. Mixed Models (LMMs, GLMMs) determined the influence of different factors (e.g. farrowing system, sow parity, management aspects) and litter characteristics on performance, including levels and causes of piglet mortality. Results: Piglet mortality was significantly influenced by farm/system. Live-born mortality ranged from 10.3 to 20.6% with stillbirths ranging from 2.5 to 5.9%. A larger litter size and higher parity resulted in higher levels of mortality regardless of system. In all systems, crushing was the main cause of piglet mortality (59%), but 31% of sows did not crush any piglets, whilst 26% crushed only one piglet and the remaining sows (43%) crushed two or more piglets. System significantly influenced crushing as a percentage of all deaths, with the system with the smallest spatial footprint (m2) compared to the other systems, recording the highest levels of crushing. Time from the start of the study influenced mortality, with significant reductions in crushing mortality (by ~ 4%) over the course of the three-year study. There was a highly significant effect of length of time (days) between moving sows into the farrowing accommodation and sows farrowing on piglet mortality (P < 0.001). The less time between sows moving in and farrowing, the higher the levels of piglet mortality, with ~ 3% increase in total mortality every five days. System effects were highly significant after adjusting for parity, litter size, and days pre-farrowing. Conclusion: These results from commercial farms demonstrate that even sows that have not been specifically selected for free farrowing are able, in many cases, to perform well in these zero-confinement systems, but that a period of adaptation is to be expected for overall farm performance. There are performance differences between the farms/systems which can be attributed to individual farm/system characteristics (e.g. pen design and management, staff expertise, pig genotypes, etc.). Higher parity sows and those producing very large litters provide a greater challenge to piglet mortality in these free farrowing systems (just as they do in crate systems). Management significantly influences performance, and ensuring sows have plenty of time to acclimatise between moving in to farrowing accommodation and giving birth is a critical aspect of improving piglet survival

High rate of lymphoma among a UK cohort of adolescents with vertically acquired HIV-1 infection transitioning to adult care in the era of antiretroviral therapy

Among an inner London UK cohort of 147 adolescents transitioning from paediatric into adult care between 2007 and 2015, a new diagnosis of lymphoma was made in five patients; incidence rate = 0.425/100 person-years (95% confidence interval = 0.424–0.426). Previously described risk factors, including low nadir CD4+ cell count and ongoing HIV-1 viraemia, appeared to be important. These data suggest that careful surveillance and a low threshold for investigating relevant symptoms continue to be essential for such patients

Brk expression may affect the differentiation status of breast cancer cells

The breast tumour kinase Brk (PTK6) is found in over two-thirds of breast cancer cell lines and tumours but is not expressed in normal mammary cells. Brk has previously been shown to play a role in regulating proliferation in breast tumour cells [1]. However, in vivo, the site of Brk expression in normal tissues is restricted to nonproliferating cells that are undergoing terminal differentiation such as those in the gut or the skin [2,3]. This led us to hypothesise that Brk expression in breast tumours could be reflective of a differentiation phenotype, especially as a previous study had shown that involucrin, a marker of terminal keratinocyte differentiation, was expressed in a subset of tumours [4]. We therefore examined involucrin expression in breast tumour cells lines and patient biopsy samples. In addition we investigated whether inducers of differentiation in keratinocytes such as prolonged culture in suspension or vitamin D3 treatment could also affect differentiation of breast tumour cells. We found that the expression of Brk in cultured cell lines correlated with involucrin expression. In addition the change in Brk expression, as a result of culture conditions, was accompanied by a change in involucrin levels. Moreover, treatment with vitamin D3 resulted in a decrease in cell numbers in the Brk-positive cell lines relative to the control treatments. The Brk-negative cell line was unaffected by vitamin D3 treatment. These data suggest that Brk and involucrin may be coregulated and that inducers of differentiation such as vitamin D3 could be considered potential therapeutic strategies