Agency, qualia and life: connecting mind and body biologically

Many believe that a suitably programmed computer could act for its own goals and experience feelings. I challenge this view and argue that agency, mental causation and qualia are all founded in the unique, homeostatic nature of living matter. The theory was formulated for coherence with the concept of an agent, neuroscientific data and laws of physics. By this method, I infer that a successful action is homeostatic for its agent and can be caused by a feeling - which does not motivate as a force, but as a control signal. From brain research and the locality principle of physics, I surmise that qualia are a fundamental, biological form of energy generated in specialized neurons. Subjectivity is explained as thermodynamically necessary on the supposition that, by converting action potentials to feelings, the neural cells avert damage from the electrochemical pulses. In exchange for this entropic benefit, phenomenal energy is spent as and where it is produced - which precludes the objective observation of qualia

Contribution of genetic effects to genetic variance components with epistasis and linkage disequilibrium

<p>Abstract</p> <p>Background</p> <p>Cockerham genetic models are commonly used in quantitative trait loci (QTL) analysis with a special feature of partitioning genotypic variances into various genetic variance components, while the F_∞genetic models are widely used in genetic association studies. Over years, there have been some confusion about the relationship between these two type of models. A link between the additive, dominance and epistatic effects in an F_∞model and the additive, dominance and epistatic variance components in a Cockerham model has not been well established, especially when there are multiple QTL in presence of epistasis and linkage disequilibrium (LD).</p> <p>Results</p> <p>In this paper, we further explore the differences and links between the F_∞and Cockerham models. First, we show that the Cockerham type models are allelic based models with a special modification to correct a confounding problem. Several important moment functions, which are useful for partition of variance components in Cockerham models, are also derived. Next, we discuss properties of the F_∞models in partition of genotypic variances. Its difference from that of the Cockerham models is addressed. Finally, for a two-locus biallelic QTL model with epistasis and LD between the loci, we present detailed formulas for calculation of the genetic variance components in terms of the additive, dominant and epistatic effects in an F_∞model. A new way of linking the Cockerham and F_∞model parameters through their coding variables of genotypes is also proposed, which is especially useful when reduced F_∞models are applied.</p> <p>Conclusion</p> <p>The Cockerham type models are allele-based models with a focus on partition of genotypic variances into various genetic variance components, which are contributed by allelic effects and their interactions. By contrast, the F_∞regression models are genotype-based models focusing on modeling and testing of within-locus genotypic effects and locus-by-locus genotypic interactions. When there is no need to distinguish the paternal and maternal allelic effects, these two types of models are transferable. Transformation between an F_∞model's parameters and its corresponding Cockerham model's parameters can be established through a relationship between their coding variables of genotypes. Genetic variance components in terms of the additive, dominance and epistatic genetic effects in an F_∞model can then be calculated by translating formulas derived for the Cockerham models.</p

Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection

Antiviral defense in the liver during acute infection with the hepatotropic virus murine cytomegalovirus (MCMV) involves complex cytokine and cellular interactions. However, the mechanism of viral sensing in the liver that promotes these cytokine and cellular responses has remained unclear. Studies here were undertaken to investigate the role of nucleic acid-sensing Toll-like receptors (TLRs) in initiating antiviral immunity in the liver during infection with MCMV. We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine whether liver antiviral defense depends on signaling through these molecules. Infection of UNC93B1 mutant mice revealed reduced production of systemic and liver proinflammatory cytokines including IFN-α, IFN-γ, IL-12 and TNF-α when compared to wild-type. UNC93B1 deficiency also contributed to a transient hepatitis later in acute infection, evidenced by augmented liver pathology and elevated systemic alanine aminotransferase levels. Moreover, viral clearance was impaired in UNC93B1 mutant mice, despite intact virus-specific CD8+ T cell responses in the liver. Altogether, these results suggest a combined role for nucleic acid-sensing TLRs in promoting early liver antiviral defense during MCMV infection

The microwave background temperature at the redshift of 2.33771

The Cosmic Microwave Background radiation is a fundamental prediction of Hot Big Bang cosmology. The temperature of its black-body spectrum has been measured at the present time, $T_{\rm CMBR,0}$ = 2.726$\pm$ 0.010 K, and is predicted to have been higher in the past. At earlier time, the temperature can be measured, in principle, using the excitation of atomic fine structure levels by the radiation field. All previous measurements however give only upper limits as they assume that no other significant source of excitation is present. Here we report the detection of absorption from the first {\sl and} second fine-structure levels of neutral carbon atoms in an isolated remote cloud at a redshift of 2.33771. In addition, the unusual detection of molecular hydrogen in several rotational levels and the presence of ionized carbon in its excited fine structure level make the absorption system unique to constrain, directly from observation, the different excitation processes at play. It is shown for the first time that the cosmic radiation was warmer in the past. We find 6.0 < T_{\rm CMBR} < 14 K at z = 2.33771 when 9.1 K is expected in the Hot Big Bang cosmology.Comment: 20 pages, 5 figures, accepted for publication in Nature, Press embargo until 1900 hrs London time (GMT) on 20 Dec 200

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Canalization and developmental stability in the Brachyrrhine mouse

The semi-dominant Br mutation affects presphenoid growth, producing the facial retrognathism and globular neurocranial vault that characterize heterozygotes. We analysed the impact of this mutation on skull shape, comparing heterozygotes to wildtype mice, to determine if the effects are skull-wide or confined to the sphenoid region targeted by the mutation. In addition, we examined patterns of variability of shape for the skull as a whole and for three regions (basicranium, face and neurocranium). We found that the Br mice differed significantly from wildtype mice in skull shape in all three regions as well as in the shape of the skull as a whole. However, the significant increases in variance and fluctuating asymmetry were found only in the basicranium of mutant mice. These results suggest that the mutation has a significant effect on the underlying developmental architecture of the skull, which produces an increase in phenotypic variability that is localized to the anatomical region in which the mean phenotype is most dramatically affected. These results suggest that the same developmental mechanisms that produce the change in phenotypic mean also produce the change in variance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75710/1/j.1469-7580.2006.00527.x.pd

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

Forests as Commons – Changing Traditions and Governance in Europe

Commons are complex institutions and exist across the world in a wide range of situations regarding locally developed governance and management systems of many different natural resources. For many people commons remain associated with Hardin’s theory concerning the “Tragedy of the Commons” (1968), in which he assumed that local users of a natural resource are unable to formulate governance and management structures concerning their own choices that took into account the long-term sustainability of the resource itself. As a result, Hardin articulated that the tragedy was that the resource would inevitably become degraded in such situations and that the solution was private or public ownership. However, across Europe many forests have for a very long period of time successfully been managed as commons, just as they have in many other parts of the world. This chapter has three main aims: It will provide an introduction to the various types of commons before going on to link the issue of commons to the traditional forest landscapes of Europe, and it will look at how the role of forests and forest landscapes has changed and how it may change further in the future