Higher Powers in Gravitation

We consider the Friedmann-Robertson-Walker cosmologies of theories of gravity that generalise the Einstein-Hilbert action by replacing the Ricci scalar, R, with some function, f(R). The general asymptotic behaviour of these cosmologies is found, at both early and late times, and the effects of adding higher and lower powers of R to the Einstein-Hilbert action is investigated. The assumption that the highest powers of R should dominate the Universe's early history, and that the lowest powers should dominate its future is found to be inaccurate. The behaviour of the general solution is complicated, and while it can be the case that single powers of R dominate the dynamics at late times, it can be either the higher or lower powers that do so. It is also shown that it is often the lowest powers of R that dominate at early times, when approach to a bounce or a Tolman solution are generic possibilities. Various examples are considered, and both vacuum and perfect fluid solutions investigated.Comment: 30 pages, 9 figure

Shifts in growth strategies reflect tradeoffs in cellular economics

The growth rate-dependent regulation of cell size, ribosomal content, and metabolic efficiency follows a common pattern in unicellular organisms: with increasing growth rates, cell size and ribosomal content increase and a shift to energetically inefficient metabolism takes place. The latter two phenomena are also observed in fast growing tumour cells and cell lines. These patterns suggest a fundamental principle of design. In biology such designs can often be understood as the result of the optimization of fitness. Here we show that in basic models of self-replicating systems these patterns are the consequence of maximizing the growth rate. Whereas most models of cellular growth consider a part of physiology, for instance only metabolism, the approach presented here integrates several subsystems to a complete self-replicating system. Such models can yield fundamentally different optimal strategies. In particular, it is shown how the shift in metabolic efficiency originates from a tradeoff between investments in enzyme synthesis and metabolic yields for alternative catabolic pathways. The models elucidate how the optimization of growth by natural selection shapes growth strategies

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

A unified treatment of single component replacement models

In this paper we discuss a general framework for single component replacement models. This framework is based on the regenerative structure of these models and by using results from renewal theory a unified presentation of the discounted and average finite and infinite horizon cost models is given. Finally, some well-known replacement models are discussed, and making use of the previous results an easy derivation of their cost functions is presented

Sensory Electrical Stimulation Improves Foot Placement during Targeted Stepping Post-Stroke

Proper foot placement is vital for maintaining balance during walking, requiring the integration of multiple sensory signals with motor commands. Disruption of brain structures post-stroke likely alters the processing of sensory information by motor centers, interfering with precision control of foot placement and walking function for stroke survivors. In this study, we examined whether somatosensory stimulation, which improves functional movements of the paretic hand, could be used to improve foot placement of the paretic limb. Foot placement was evaluated before, during, and after application of somatosensory electrical stimulation to the paretic foot during a targeted stepping task. Starting from standing, twelve chronic stroke participants initiated movement with the non-paretic limb and stepped to one of five target locations projected onto the floor with distances normalized to the paretic stride length. Targeting error and lower extremity kinematics were used to assess changes in foot placement and limb control due to somatosensory stimulation. Significant reductions in placement error in the medial–lateral direction (p = 0.008) were observed during the stimulation and post-stimulation blocks. Seven participants, presenting with a hip circumduction walking pattern, had reductions (p = 0.008) in the magnitude and duration of hip abduction during swing with somatosensory stimulation. Reductions in circumduction correlated with both functional and clinical measures, with larger improvements observed in participants with greater impairment. The results of this study suggest that somatosensory stimulation of the paretic foot applied during movement can improve the precision control of foot placement

Взаимосвязь ожирения и нарушений углеводного обмена с синдромом обструктивного апноэ во сне

Представлены литературные данные клинических исследований, в которых синдром обструктивного апноэ во сне (СОАС) рассматривается как фактор риска развития нарушений углеводного обмена, в том числе сахарного диабета 2−го типа. Анализируется взаимосвязь наиболее значимых факторов, влияющих на прогрессирование нарушений углеводного обмена у пациентов с СОАС. Приведен анализ данных о связи СОАС с диабетической автономной нейропатией и инсулинорезистентностью. Рассматривается возможность применения СРАР−терапии для коррекции метаболических нарушений у пациентов с сахарным диабетом.Представлено літературні дані клінічних досліджень, у яких синдром обструктивного апное під час сну (СОАС) розглянуто як фактор ризику розвитку порушень вуглеводного обміну, у тому числі цукрового діабету 2−го типу. Аналізується взаємозв'язок найбільш значущих факторів, що впливають на прогресування порушень вуглеводного обміну у пацієнтів із СОАС. Наведено аналіз даних про зв'язок СОАС із діабетичною автономною нейропатією та інсулінорезистентністю. Розглянуто можливість використання СРАР−терапії для корекції метаболічних порушень у пацієнтів із цукровим діабетом.Literature data about clinical trials, in which sleep apnea syndrome (SAS) is featured as a risk factor of carbohydrate metabolism disorders, including type 2 diabetes mellitus, are presented. Association of the most significant factors influencing the progress carbohydrate metabolism disorders in patients with SAS is analyzed. The data about the association of SAS and diabetic autonomous neuropathy and insulin resistance are featured. Possibility to use CPAP therapy for correction of metabolic disorders in patients with diabetes mellitus is discussed

Genetic Covariance Structure of Reading, Intelligence and Memory in Children

This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained by a common genetic factor for reading performance, IQ, WM and STM and a genetic factor that only influenced reading performance and verbal memory. Genetic variation explained 83% of the variation in reading performance; most of this genetic variance was explained by variation in IQ and memory performance. We hypothesize, based on these results, that children with reading problems possibly can be divided into three groups: (1) children low in IQ and with reading problems; (2) children with average IQ but a STM deficit and with reading problems; (3) children with low IQ and STM deficits; this group may experience more reading problems than the other two