Nonstatistical dynamics on potentials exhibiting reaction path bifurcations and valley-ridge inflection points

We study reaction dynamics on a model potential energy surface exhibiting post-transition state bifurcation in the vicinity of a valley ridge inflection point. We compute fractional yields of products reached after the VRI region is traversed, both with and without dissipation. It is found that apparently minor variations in the potential lead to significant changes in the reaction dynamics. Moreover, when dissipative effects are incorporated, the product ratio depends in a complicated and highly non-monotonic fashion on the dissipation parameter. Dynamics in the vicinity of the VRI point itself play essentially no role in determining the product ratio, except in the highly dissipative regime.Comment: 33 pages, 10 figures, corrected the author name in reference [6

Distinct Mitochondrial Pathologies Caused by Mutations of the Proximal Tubular Enzymes EHHADH and GATM

The mitochondria of the proximal tubule are essential for providing energy in this nephron segment, whose ATP generation is almost exclusively oxygen dependent. In addition, mitochondria are involved in a variety of metabolic processes and complex signaling networks. Proximal tubular mitochondrial dysfunction can therefore affect renal function in very different ways. Two autosomal dominantly inherited forms of renal Fanconi syndrome illustrate how multifaceted mitochondrial pathology can be: Mutation of EHHADH, an enzyme in fatty acid metabolism, results in decreased ATP synthesis and a consecutive transport defect. In contrast, mutations of GATM, an enzyme in the creatine biosynthetic pathway, leave ATP synthesis unaffected but do lead to mitochondrial protein aggregates, inflammasome activation, and renal fibrosis with progressive renal failure. In this review article, the distinct pathophysiological mechanisms of these two diseases are presented, which are examples of the spectrum of proximal tubular mitochondrial diseases

EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies

In 2009, two groups independently linked human mutations in the inwardly rectifying K+ channel Kir4.1 (gene name KCNJ10) to a syndrome affecting the central nervous system (CNS), hearing, and renal tubular salt reabsorption. The autosomal recessive syndrome has been named EAST (epilepsy, ataxia, sensorineural deafness, and renal tubulopathy) or SeSAME syndrome (seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance), accordingly. Renal dysfunction in EAST/SeSAME patients results in loss of Na+, K+, and Mg2+ with urine, activation of the renin–angiotensin–aldosterone system, and hypokalemic metabolic alkalosis. Kir4.1 is highly expressed in affected organs: the CNS, inner ear, and kidney. In the kidney, it mostly forms heteromeric channels with Kir5.1 (KCNJ16). Biallelic loss-of-function mutations of Kir5.1 can also have disease significance, but the clinical symptoms differ substantially from those of EAST/SeSAME syndrome: although sensorineural hearing loss and hypokalemia are replicated, there is no alkalosis, but rather acidosis of variable severity; in contrast to EAST/SeSAME syndrome, the CNS is unaffected. This review provides a framework for understanding some of these differences and will guide the reader through the growing literature on Kir4.1 and Kir5.1, discussing the complex disease mechanisms and the variable expression of disease symptoms from a molecular and systems physiology perspective. Knowledge of the pathophysiology of these diseases and their multifaceted clinical spectrum is an important prerequisite for making the correct diagnosis and forms the basis for personalized therapies

Groundwater microflora of the Aptian-Cenomanian deposits at the Igolsko-Talovoe field in Tomsk Region

The authors have studied the microbiological composition of the groundwater of the Aptian-Cenomanian deposits in the territory of the Igolsko-Talovoe field in Tomsk Region. The detected diversity of the physiological groups of bacteria can be a corrosive component for waters used in the reservoir pressure maintenance system. The research findings have allowed making conclusions about the need to study the contribution of all microorganisms inhabiting the waters of the Aptian-Cenomanian deposits to corrosion

Photothermal treatment of cutaneous lesions

This thesis reviews the understanding of the processes involved in the laser treatment of cutaneous blemishes. The current treatment protocol for the treatment of vascular lesions - double scanning with transient blanching used at St George's Hospital is shown to give excellent results. The protocol takes advantage of the precise control provided by the SCANALL automatic scanner and the 5 W, 578 nm output of the copper vapour laser. The clinical endpoint - transient blanching - is shown to be due to a temporary halting of blood flow (probably by vasoconstriction) rather than coagulation necrosis of overlying tissues. Various models of the laser treatment of vascular lesions are presented and examined. A histological study of the double scanning, transient blanching protocol shows that tissue damage is confined to vascular and perivascular tissue. Cosmetic lightening is due to a reduction in both the number and size of the vessels in the upper dermis. The protocol is also investigated by interview and postal survey. The incidence of adverse effects is small. For example, there are only two 1 cm² adverse skin texture changes in 64000cm² of treated area. Patients receiving treatment for telangiectasia and spider naevus are satisfied with the outcome after one or two treatments, but many with port-wine stain cease treatment after four sessions when government funding runs out. Patient perception of the success is compared with the surgeon's perception. Patients often needed to be reminded of the size and severity of their original lesion with a photograph. The thesis reports on a parallel investigation of the use of millisecond scale pulses of white light for the treatment of tattoos. A xenon flash-lamp system is designed, constructed, and used in a clinical trial. This includes building pulse forming networks to produce rectangular current pulses of differing lengths. During the clinical trial the system produced a strong inflammatory response in the skin adjacent to the pigment, and lightening of the tattoo. Modelling, histology and other literature studies lead to the conclusion that the pulse length is too long to cause the explosive rupture of pigment-containing cells observed after Q-switched laser treatment, and too short to cause sufficient necrosis and phagocytosis of the pigment-containing cells for it to be useful clinically. The thesis also describes the construction of a device to measure muscle tension during tendon transfer surgery. The device uses diffraction to measure the separation of the fundamental unit of muscle tissue - the sarcomere

Media, Capabilities, and Justification

In this paper, I evaluate the ‘capability approach’ developed by Amartya Sen and Martha Nussbaum as a normative perspective for critical media research. The concept of capabilities provides a valuable way of assessing media and captures important aspects of the relationship between media and equality. However, following Rainer Forst’s critique of outcome- oriented approaches to justice, I argue the capability approach needs to pay more attention to questions of power and process. In particular, when it comes to deciding which capabilities media should promote and what media structure and practices should promote them, the capability approach must accept the priority of deliberative and democratic processes of justification. Once we do this, we are urged to situate the concept of capabilities within a more process-oriented view of justice, focused not on capabilities as such, but on outlining the conditions required for justificatory equality. After discussing the capability approach, I will outline the process-oriented theory of justice Forst has developed around the idea of the ‘right to justification’. While Forst does not discuss media in depth, I argue his theory of justice can provide a valuable alternative normative standpoint for the critical media research

On Justification, Idealization, and Discursive Purchase

Conceptions of acceptability-based moral or political justification take it that authoritative acceptability, widely conceived, constitutes, or contributes to, validity, or justification. There is no agreement as to what bar for authoritativeness such justification may employ. The paper engages the issue in relation to (i) the level of idealization that a bar for authoritativeness, ψ, imparts to a standard of acceptability-based justification, S, and (ii) the degree of discursive purchase of the discursive standing that S accords to people when it builds ψ. I argue that (i) and (ii) are interdependent: high idealization values entail low discursive purchase, while high degrees of purchase require low idealization values. I then distinguish between alethic conceptions of justification that prioritize ends that commit to high idealization values, and recognitive conceptions that favor high discursive purchase. On this basis, I argue for a moderately recognitivist constraint on idealization. To render the recognitive discursive minimum available to relevant people at the site of justification, S should set ψ low enough so that it is a genuine option for actual people to reject relevant views in ways that S recognizes as authoritative. (The Appendix applies this to a Forst-type view of reciprocity of reasons to draw out some limitations of this view.) [Draft available from author on request.

Bottlenecks to vibrational energy flow in OCS: Structures and mechanisms

Finding the causes for the nonstatistical vibrational energy relaxation in the planar carbonyl sulfide (OCS) molecule is a longstanding problem in chemical physics: Not only is the relaxation incomplete long past the predicted statistical relaxation time, but it also consists of a sequence of abrupt transitions between long-lived regions of localized energy modes. We report on the phase space bottlenecks responsible for this slow and uneven vibrational energy flow in this Hamiltonian system with three degrees of freedom. They belong to a particular class of two-dimensional invariant tori which are organized around elliptic periodic orbits. We relate the trapping and transition mechanisms with the linear stability of these structures.Comment: 13 pages, 13 figure