The Learning Curve and Optimal Production Under Uncertainty

This paper examines the implications of the learning curve in a world of uncertainty. We consider a competitive firm whose costs decline with cumulative output. Because the price of the firm's output evolves stochastically, future production and cumulative output are unknown, and are contingent on future prices and costs. We derive an optimal decision rule that maximizes the firm's market value: produce when price exceeds a critical level, which is a declining function of cumulative output. We show how the shadow value of cumulative production, as well as the total value of the firm, depend on the volatility of price and other parameters. Over the relevant range of prices, uncertainty reduces the shadow value of cumulative production, and therefore increases the critical price required for the firm to begin producing.

Time to Build, Option Value, and Investment Decisions

Many investment projects have the following characteristics: (i) spending decisions and cash outlays occur sequentially over time, (ii) there is a maximum rate at which outlays and construction can proceed -- it takes "time to build," and (iii) the project yields no cash return until it is actually completed. Furthermore, the pattern of investment outlays is usually flexible,and can be adjusted as new information arrives. For such projects traditional discounted cash flow criteria, which treat the spending pattern as fixed, are inadequate as a guide for project evaluation. This paper develops an explicit model of investment projects with these characteristics, and uses option pricing methods to derive optimal decision rules for investment outlays over the entire construction program. Numerical solutions are used to demonstrate how time to build, opportunity cost, and uncertainty interact in affecting the investment decision. We show that with moderate levels of uncertainty over the future value of the completed project, a simple NPV rule could lead to gross over-investment. Also, we show how the contingent nature of the investment program magnifies the depressive effect of increased uncertainty on investment spending.

A comparative study of IP Versions 4, 5, and 6

This research examines the Internet Protocol (IP) versions 4, 5, and 6, as well as the differences between them and which protocol is more suitable for the future of the internet, among other things. Through this research, we have established the most advantageous characteristics of these protocols, as well as the specific elements that each protocol uses to allow the internet network to operate at maximum capacity. The main aim of this study is to discover which of the internet protocols, IPv4, IPv5, or IPv6, is the most widely used. IPv4 is the most widely used protocol, followed by IPv5. The most essential elements of getting a more relevant job on the internet network are highlighted in this article. It all comes down to how IP protocols operate and what they accomplish

Neuronal response in Alzheimer's and Parkinson's disease: the effect of toxic proteins on intracellular pathways

Accumulation of protein aggregates is the leading cause of cellular dysfunction in neurodegenerative disorders. Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, Prion disease and motor disorders such as amyotrophic lateral sclerosis, present with a similar pattern of progressive neuronal death, nervous system deterioration and cognitive impairment. The common characteristic is an unusual misfolding of proteins which is believed to cause protein deposition and trigger degenerative signals in the neurons. A similar clinical presentation seen in many neurodegenerative disorders suggests the possibility of shared neuronal responses in different disorders. Despite the difference in core elements of deposits in each neurodegenerative disorder, the cascade of neuronal reactions such as activation of glycogen synthase kinase-3 beta, mitogen-activated protein kinases, cell cycle re-entry and oxidative stress leading to a progressive neurodegeneration are surprisingly similar. This review focuses on protein toxicity in two neurodegenerative diseases, AD and PD. We reviewed the activated mechanisms of neurotoxicity in response to misfolded beta-amyloid and α-synuclein, two major toxic proteins in AD and PD, leading to neuronal apoptosis. The interaction between the proteins in producing an overlapping pathological pattern will be also discussed.Shohreh Majd, John H. Power and Hugh J.M. Grantha

The impact of tau hyperphosphorylation at Ser(262) on memory and learning after global brain ischaemia in a rat model of reversible cardiac arrest

An increase in phosphorylated tau (p-tau) is associated with Alzheimer's disease (AD), and brain hypoxia. Investigation of the association of residue-specific tau hyperphosphorylation and changes in cognition, leads to greater understanding of its potential role in the pathology of memory impairment. The aims of this study are to investigate the involvement of the main metabolic kinases, Liver Kinase B1 (LKB1) and Adenosine Monophosphate Kinase Protein Kinase (AMPK), in tau phosphorylation-derived memory impairment, and to study the potential contribution of the other tau kinases and phosphatases including Glycogen Synthase Kinase (GSK-3β), Protein kinase A (PKA) and Protein Phosphatase 2A (PP2A). Spatial memory and learning were tested in a rat global brain ischemic model of reversible cardiac arrest (CA). The phosphorylation levels of LKB1, AMPK, GSK-3β, PP2A, PKA and tau-specific phosphorylation were assessed in rats, subjected to ischaemia/reperfusion and in clinically diagnosed AD and normal human brains. LKB1 and AMPK phosphorylation increased 4 weeks after CA as did AMPK related p-tau (Ser262). The animals showed unchanged levels of GSK-3β specific p-tau (Ser202/Thr205), phospho-PP2A (Tyr307), total GSK-3β, PP2A, phospho-cAMP response element-binding protein (CREB) which is an indicator of PKA activity, and no memory deficits. AD brains had hyperphosphorylated tau in all the residues of Ser262, Ser202 and Thr205, with increased phosphorylation of both AMPK (Thr172) and GSK-3β (Ser9), and reduced PP2A levels. Our data suggests a crucial role for a combined activation of tau kinases and phosphatases in adversely affecting memory and that hyperphosphorylation of tau in more than one specific site may be required to create memory deficits.Shohreh Majd, John H.T.Power, Simon A.Koblar, Hugh J.M.Grantha

Hypertrophic pyloric stenosis, an unusual presentation and rare association: case report and literature review

Hypertrophic pyloric stenosis (HPS) is a commonly encountered surgical condition that occurs in infancy, but not in neonates. This report describes a 10-day-old male patient with atypical presentation of HPS, with an incidental diagnosis of eventration of the left diaphragm. The symptoms were present since birth with nonprojectile, nonbilious vomiting and gastric distension. A contrast study showed a gastric outlet obstruction with the possibility of gastric volvulus. Emergency surgery established the diagnosis. To the best of our knowledge, the association of HPS with diaphragmatic defect and gastric volvulus is rare, and few cases have been reported in the literature

Early glycogen synthase kinase-3beta and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway

Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This study assessed the effects of global brain ischaemia/reperfusion on the immediate status of p-tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser(396) and Ser(262) after 2 min of ischaemia, which did not recover during the first two hours of reperfusion, while the tau phosphorylation at GSK-3β sensitive but AMPK insensitive residues, Ser(202) /Thr(205) (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK-3β and PP2A during similar episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischaemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p-AMPK, in ischaemic/reperfusion groups. This suggests the involvement of AMPK in changing the p-tau levels, indicating that tau dephosphorylation following ischaemia is not dependent on GSK-3β or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction in AMPK activity is a possible early mechanism responsible for tau dephosphorylation.Shohreh Majd, John H. T. Power, Simon A. Koblar and Hugh J. M. Grantha

Histomorphometrical study of silver carp fish testis in two age classes

In this research, morphological and histomorphometrical structure of testis of 20 silver male carp fish were studied in two classes or groups. Group1 was composed of 10 fish with average (±SD) weight of 1.247+0.656kg and average(±SD) length of 43.675+1.414cm with about 2 years age, Group2 was composed of 10 fish with average(±SD) weight of 5.716+0.519kg and average(±SD) length of 81.5+1.643cm. Average (±SD) weight of testis were 2.34+1.47gr and 83.33+25.81gr with average (±SD) GSI of 0.187+0.224 and 1.457+4.974 in groups 1 and 2 respectively. Samples from testis were taken by maximum thickness of 0.5cm and after fixation in bouin , s fixative and 5-6µm thickness section were made routine paraffin embedding method and stained by Hematoxylin-Eosin and PAS staining. The microscopic results showed that the silver carp testis was lobular and cystic type in two groups. In group 1, there was no spermatozoon activity and PGCs were only germ cells in the cysts. But in group2, the numbers of PGCs were decreased significantly and spermatogenic cells were seen in different phases including spermatogonia, primary and secondary spermatocysts, early and late spermatid, and spermatozoa which each one was located in a separated cyst. There was no significant difference in nucleus diameter of PGCs in testis of group1 (6.97+0.438µ) and group (6.13+0.438µ). In group2, the nucleolus diameter of spermatogonia was 2.97+0.112µm, primary spermatocyt 3.59+0.107µ, early spermatid 1.59+0.761µ, late spermatid 1.24+0.132µ, spermatozoa 1.16+0.054µ, and the length of spermatozoia 17.412+1.946µ. The interesting finding was immature testis in fish of group 1 with average weigh (1.247+0.656kg) and average length (43.675+1.414cm) in about 2 years age and mature testis in fish of group 2 with average weight of (5.716+0.519kg) and average length of (81.5+1.643cm) with about 4 years age in Khuzestan climate conditions