Allocation under dictatorship : research in Stalin’s archives

We survey recent research on the Soviet economy in the state, party, and military archives of the Stalin era. The archives have provided rich new evidence on the economic arrangements of a command system under a powerful dictator including Stalin’s role in the making of the economic system and economic policy, Stalin’s accumulation objectives and the constraints that limited his power to achieve them, the limits to administrative allocation, the information flows and incentives that governed the behavior of economic managers, the scope and significance of corruption and market-oriented behavior, and the prospects for economic reform

The Role of Dendritic Cell Subsets and Innate Immunity in the Pathogenesis of Type 1 Diabetes and Other Autoimmune Diseases

Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are four main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in autoimmune pathogenesis and regulation, as well as the genetic and environmental signals that influence their function. Specific topics to be addressed include impact of susceptibility loci on DC subsets, alterations in DC subset development, the role of infection- and host-derived innate inflammatory signals, and the role of the intestinal microbiota on DC phenotype. The effects of these various signals on disease progression and the relative effects of DC subset composition and maturation level of DCs will be examined. These areas will be explored using examples from several autoimmune diseases but will focus mainly on type 1 diabetes

Climate fluctuations of tropical coupled system: The role of ocean dynamics

The tropical oceans have long been recognized as the most important region for large-scale ocean–atmosphere interactions, giving rise to coupled climate variations on several time scales. During the Tropical Ocean Global Atmosphere (TOGA) decade, the focus of much tropical ocean research was on understanding El Niño–related processes and on development of tropical ocean models capable of simulating and predicting El Niño. These studies led to an appreciation of the vital role the ocean plays in providing the memory for predicting El Niño and thus making seasonal climate prediction feasible. With the end of TOGA and the beginning of Climate Variability and Prediction (CLIVAR), the scope of climate variability and predictability studies has expanded from the tropical Pacific and ENSO-centric basis to the global domain. In this paper the progress that has been made in tropical ocean climate studies during the early years of CLIVAR is discussed. The discussion is divided geographically into three tropical ocean basins with an emphasis on the dynamical processes that are most relevant to the coupling between the atmosphere and oceans. For the tropical Pacific, the continuing effort to improve understanding of large- and small-scale dynamics for the purpose of extending the skill of ENSO prediction is assessed. This paper then goes beyond the time and space scales of El Niño and discusses recent research activities on the fundamental issue of the processes maintaining the tropical thermocline. This includes the study of subtropical cells (STCs) and ventilated thermocline processes, which are potentially important to the understanding of the low-frequency modulation of El Niño. For the tropical Atlantic, the dominant oceanic processes that interact with regional atmospheric feedbacks are examined as well as the remote influence from both the Pacific El Niño and extratropical climate fluctuations giving rise to multiple patterns of variability distinguished by season and location. The potential impact of Atlantic thermohaline circulation on tropical Atlantic variability (TAV) is also discussed. For the tropical Indian Ocean, local and remote mechanisms governing low-frequency sea surface temperature variations are examined. After reviewing the recent rapid progress in the understanding of coupled dynamics in the region, this study focuses on the active role of ocean dynamics in a seasonally locked east–west internal mode of variability, known as the Indian Ocean dipole (IOD). Influences of the IOD on climatic conditions in Asia, Australia, East Africa, and Europe are discussed. While the attempt throughout is to give a comprehensive overview of what is known about the role of the tropical oceans in climate, the fact of the matter is that much remains to be understood and explained. The complex nature of the tropical coupled phenomena and the interaction among them argue strongly for coordinated and sustained observations, as well as additional careful modeling investigations in order to further advance the current understanding of the role of tropical oceans in climate

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

A century of exercise physiology : key concepts in regulation of glycogen metabolism in skeletal muscle.

Glycogen is a branched, glucose polymer and the storage form of glucose in cells. Glycogen has traditionally been viewed as a key substrate for muscle ATP production during conditions of high energy demand and considered to be limiting for work capacity and force generation under defined conditions. Glycogenolysis is catalyzed by phosphorylase, while glycogenesis is catalyzed by glycogen synthase. For many years, it was believed that a primer was required for de novo glycogen synthesis and the protein considered responsible for this process was ultimately discovered and named glycogenin. However, the subsequent observation of glycogen storage in the absence of functional glycogenin raises questions about the true role of the protein. In resting muscle, phosphorylase is generally considered to be present in two forms: non-phosphorylated and inactive (phosphorylase b) and phosphorylated and constitutively active (phosphorylase a). Initially, it was believed that activation of phosphorylase during intense muscle contraction was primarily accounted for by phosphorylation of phosphorylase b (activated by increases in AMP) to a, and that glycogen synthesis during recovery from exercise occurred solely through mechanisms controlled by glucose transport and glycogen synthase. However, it now appears that these views require modifications. Moreover, the traditional roles of glycogen in muscle function have been extended in recent years and in some instances, the original concepts have undergone revision. Thus, despite the extensive amount of knowledge accrued during the past 100 years, several critical questions remain regarding the regulation of glycogen metabolism and its role in living muscle

Maximal exercise tolerance after induced alkalosis

Eight healthy males performed two rides to exhaustion at a work load corresponding to 125% Q02 max, one hr after ingesting either NaHCO3 (E) or NaCl (C). Mean + SE pre-exercise blood pH, HCO3 and base excess (BE) values were respectively 7.42 + 0.01, 28.2 + 1.5 mmol/l and 2.02 + 0.1 mmol/l for the E condition, and 7.39 + 0.01, 24.4 + 0.7 mmol/l and -0.4 + 0.7 mmol/l for the C condition (P < 0.05 for all variables). Cycling time to exhaustion (E = 100.66.1; C = 98.6 + 5.7 sec) and total "02 during recovery (E 17.7 + 0.9; C = 17.3 + 0.8 1/30 min) did not differ between treatments. Blood pH, HCO3 and BE were significantly higher while the hydrogen ion to lactate ratio (LH+I/ELAI) was significantly lower in E than in C during recovery. Blood LA levels were also greater in E than in C during the latter part of recovery although peak individual values were not significantly different between trials CE = 14.4 + 0.4; C = 13.3 + 0.0 mmol /1) . In view of the insignificant differences in cycling time, peakLA production was greater in E than in C. Rather it individual LA and total recovery 002, it is not likely that Given this protocol, alkalosis does not help to sustain an appears that LA efflux was enhanced by the NaHCO3 feeding. Additionally, the return of the acid-base status in blood to resting conditions was more rapid during alkalosis does not help to sustain an intense exercise bout. These data suggest, however, that NaHCO3 may be of benefit following repeated work bouts.Thesis (M.A.

Maximal exercise tolerance after induced alkalosis

Eight healthy males performed two rides to exhaustion at a work load corresponding to 125% Q02 max, one hr after ingesting either NaHCO3 (E) or NaCl (C). Mean + SE pre-exercise blood pH, HCO3 and base excess (BE) values were respectively 7.42 + 0.01, 28.2 + 1.5 mmol/l and 2.02 + 0.1 mmol/l for the E condition, and 7.39 + 0.01, 24.4 + 0.7 mmol/l and -0.4 + 0.7 mmol/l for the C condition (P < 0.05 for all variables). Cycling time to exhaustion (E = 100.66.1; C = 98.6 + 5.7 sec) and total "02 during recovery (E 17.7 + 0.9; C = 17.3 + 0.8 1/30 min) did not differ between treatments. Blood pH, HCO3 and BE were significantly higher while the hydrogen ion to lactate ratio (LH+I/ELAI) was significantly lower in E than in C during recovery. Blood LA levels were also greater in E than in C during the latter part of recovery although peak individual values were not significantly different between trials CE = 14.4 + 0.4; C = 13.3 + 0.0 mmol /1) . In view of the insignificant differences in cycling time, peakLA production was greater in E than in C. Rather it individual LA and total recovery 002, it is not likely that Given this protocol, alkalosis does not help to sustain an appears that LA efflux was enhanced by the NaHCO3 feeding. Additionally, the return of the acid-base status in blood to resting conditions was more rapid during alkalosis does not help to sustain an intense exercise bout. These data suggest, however, that NaHCO3 may be of benefit following repeated work bouts.Thesis (M.A.

The role of glycogen phosphorylase in glycogen biogenesis in skeletal muscle after exercise

Initially it was believed that phosphorylase was responsible for both glycogen breakdown and synthesis in the living cell. The discovery of glycogen synthase and McArdle's disease (lack of phosphorylase activity), together with the high Pi/glucose 1-P ratio in skeletal muscle, demonstrated that glycogen synthesis could not be attributed to reversal of the phosphorylase reaction. Rather, glycogen synthesis was attributable solely to the activity of glycogen synthase, subsequent to the transport of glucose into the cell. However, the well-established observation that phosphorylase was inactivated (i.e., dephosphorylated) during the initial recovery period after prior exercise, when the rate of glycogen accumulation is highest and independent of insulin, suggested that phosphorylase could play an active role in glycogen accumulation. But the quantitative contribution of phosphorylase inactivation was not established until recently, when studying isolated murine muscle preparations during recovery from repeated contractions at temperatures ranging from 25 to 35 °C. Thus, in both slow-twitch, oxidative and fast-twitch, glycolytic muscles, inactivation of phosphorylase accounted for 45%–75% of glycogen accumulation during the initial hours of recovery following repeated contractions. Such data indicate that phosphorylase inactivation may be the most important mechanism for glycogen accumulation under defined conditions. These results support the initial belief that phosphorylase plays a quantitative role in glycogen formation in the living cell. However, the mechanism is not via activation of phosphorylase, but rather via inactivation of the enzyme