Effects of inflation and time value of money on an inventory system with deteriorating items and partially backlogged shortages

As the long arm of the grinding, deep financial crisis continues to haunt the global economy, the effects of inflation and time value of money cannot be oblivious to an inventory system. Inflation, defined as a general rise in the prices of goods and services over a period of time, has monetary depreciation as one of its major side effects. And, since inventories correspond to substantial investment in capital for any organization, it would be unethical if the effects of inflation and time value of money are not considered while determining the optimal inventory policy. Moreover, deterioration of items is a phenomenon which cannot be ignored, as it may yield misleading results. Further, under the inflationary conditions, the different cost parameters including the price are bound to vary from cycle to cycle over the planning horizon. Another important factor is shortages which no retailer would prefer, and in practice are partially backlogged and partially lost. In order to convert the lost sales into sales, the retailer offers such customers an incentive, by charging them the price prevailing at the time of placing an order, instead of the current inflated price. Therefore, bearing in mind these facts, the present paper develops an inventory model for a retailer dealing with deteriorating items under inflationary conditions over a fixed planning horizon. The objective is to derive the optimal number of cycles and cycle length that maximizes the net present value of the total profit over a fixed planning horizon. An appropriate algorithm has been proposed to obtain the optimal solution. Finally, a numerical example is provided to illustrate the proposed model. Sensitivity analysis of the optimal solution with respect to major parameters is carried out and some managerial inferences have been presented

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Molecular mechanisms of mammalian cell survival and differentiation

Cellular and developmental processes are regulated by extracellular and intracellular signals that are mediated by networks of signaling pathways. In recent years, microRNAs have also emerged as a class of critical modulators of the same processes. For my thesis studies, I focused on regulatory mechanisms underlying mammalian cell survival and differentiation. In particular, I investigated the regulation of mammalian target of rapamycin (mTOR), an evolutionarily conserved Ser/Thr kinase that integrates signals from nutrient availability, growth factors, differentiation inducers, and various types of stress, to control a wide range of biological processes. Separately, I also discovered a novel microRNA regulator of myogenic differentiation, microRNA-146b. Emerging evidence implicates the deregulation of mTOR signaling in a variety of diseases including cancer and diabetes, underscoring the importance to fully understand the regulation of mTOR signaling. mTOR forms two distinct complexes known as mTORC1 and mTORC2. mTORC2 controls a wide range of cellular functions, but the regulation of its signaling remains incompletely understood. In Chapter 2, I identified XPLN, a RhoGEF, as an endogenous inhibitor of mTORC2 kinase activity towards Akt. Furthermore, I showed that the GEF activity of XPLN is dispensable for its regulation of mTORC2 and Akt, whereas an N-terminal 125-amino acid fragment of XPLN is both necessary and sufficient for the inhibition of mTORC2. XPLN negatively regulates myoblast differentiation and cell survival by suppressing mTORC2 and Akt, and could likely be an important player in many other aspects of biology and diseases involving mTORC2 and Akt. Next, I set out to search for a mechanism by which XPLN could be regulated in cells in order to allow Akt activation following growth factor stimulation. In Chapter 3, I investigated the subcellular localization of XPLN, and found it to be localized throughout the cell but concentrated in the nucleus. I subsequently manipulated the location by tagging various localization signals to XPLN and examined the functional consequence. Furthermore, I studied the function and localization of alternative splice isoforms of XPLN. Given the well-known hyperactivation of Akt in many human tumors, I probed a potential role of XPLN in cancer by analyzing its protein levels in various cancer cell lines, as described in Appendix A. Knockdown and overexpressed XPLN were also performed in cancer cells to probe the effects on Akt phosphorylation. Finally, as described in Appendix B, I am in the process of generating XPLN knockout mice using the TALEN technology, in order to facilitate future in vivo studies of XPLN. In Chapter 4, I identified and characterized microRNA-146b (miR-146b) as a novel positive regulator of skeletal myogenesis. Inhibition of miR-146b led to reduced myoblast differentiation, whereas overexpression of miR-146b enhanced differentiation. In addition, miR-146b directly targets Smad4, Hmga2, and Notch1 in muscle cells. The expression of miR-146b and its target genes was inversely correlated during myoblast differentiation and muscle regeneration, suggesting that these genes most likely mediate the myogenic function of miR-146b. In conclusion, my studies have uncovered novel regulators and mechanisms of mammalian cell survival and myogenic differentiation, and laid the foundation for future investigations

Effects of inflation and time value of money on an inventory system with deteriorating items and partially backlogged shortages

As the long arm of the grinding, deep financial crisis continues to haunt the global economy, the effects of inflation and time value of money cannot be oblivious to an inventory system. Inflation, defined as a general rise in the prices of goods and services over a period of time, has monetary depreciation as one of its major side effects. And, since inventories correspond to substantial investment in capital for any organization, it would be unethical if the effects of inflation and time value of money are not considered while determining the optimal inventory policy. Moreover, deterioration of items is a phenomenon which cannot be ignored, as it may yield misleading results. Further, under the inflationary conditions, the different cost parameters including the price are bound to vary from cycle to cycle over the planning horizon. Another important factor is shortages which no retailer would prefer, and in practice are partially backlogged and partially lost. In order to convert the lost sales into sales, the retailer offers such customers an incentive, by charging them the price prevailing at the time of placing an order, instead of the current inflated price. Therefore, bearing in mind these facts, the present paper develops an inventory model for a retailer dealing with deteriorating items under inflationary conditions over a fixed planning horizon. The objective is to derive the optimal number of cycles and cycle length that maximizes the net present value of the total profit over a fixed planning horizon. An appropriate algorithm has been proposed to obtain the optimal solution. Finally, a numerical example is provided to illustrate the proposed model. Sensitivity analysis of the optimal solution with respect to major parameters is carried out and some managerial inferences have been presented

Optimal replenishment policy for fuzzy inventory model with deteriorating items and allowable shortages under inflationary conditions

This study develops an inventory model to determine ordering policy for deteriorating items with constant demand rate under inflationary condition over a fixed planning horizon. Shortages are allowed and are partially backlogged. In today’s wobbling economy, especially for long term investment, the effects of inflation cannot be disregarded as uncertainty about future inflation may influence the ordering policy. Therefore, in this paper a fuzzy model is developed that fuzzify the inflation rate, discount rate, deterioration rate, and backlogging parameter by using triangular fuzzy numbers to represent the uncertainty. For Defuzzification, the well known signed distance method is employed to find the total profit over the planning horizon. The objective of the study is to derive the optimal number of cycles and their optimal length so to maximize the net present value of the total profit over a fixed planning horizon. The necessary and sufficient conditions for an optimal solution are characterized. An algorithm is proposed to find the optimal solution. Finally, the proposed model has been validated with numerical example. Sensitivity analysis has been performed to study the impact of various parameters on the optimal solution, and some important managerial implications are presented

OPTIMIZATION OF FUTURISTIC DECISION PRIORITIES FOR CANCER CONTROL IN INDIA

Cancer population is increasing with tremendous pace in our country. If the present state of disease continues due to lack of awareness, diagnostic and treatment facilities, inadequate human resources and ignorance about carcinogenic factors, then Cancer will be the biggest killer disease in near future. This paper presents an application of MultiCriteria Futuristic Decision Making (M.C.F.D.M.). Methodology to optimize futuristic decision priorities for control of Cancer Population from the face of India by the year 2020 A.D

MicroRNA-146b Promotes Myogenic Differentiation and Modulates Multiple Gene Targets in Muscle Cells

<div><p>MicroRNAs are established as crucial modulators of skeletal myogenesis, but our knowledge about their identity and targets remains limited. In this study, we have identified microRNA-146b (miR-146b) as a novel regulator of skeletal myoblast differentiation. Following up on a previous microRNA profiling study, we establish that the expression of miR-146b is up-regulated during myoblast differentiation in vitro and muscle regeneration in vivo. Inhibition of miR-146b led to reduced myoblast differentiation, whereas overexpression of miR-146b enhanced differentiation. Computational prediction combined with gene expression information has revealed candidates for miR-146b targets in muscles. Among them, the expression of Smad4, Notch1, and Hmga2 are significantly suppressed by miR-146b overexpression in myocytes. In addition, expression levels of Smad4, Notch1 and Hmga2 are decreased during myoblast differentiation and muscle regeneration, inversely correlating to the levels of miR-146b. Importantly, inhibition of endogenous miR-146b prevents the down-regulation of Smad4, Notch1 and Hmga2 during differentiation. Furthermore, miR-146b directly targets the microRNA response elements (MREs) in the 3′UTR of those genes as assessed by reporter assays. Reporters with the seed regions of MREs mutated are insensitive to miR-146b, further confirming the specificity of targeting. In conclusion, miR-146b is a positive regulator of myogenic differentiation, possibly acting through multiple targets.</p></div

THE IMPACT OF TREATMENT ON THE QUALITY OF LIFE IN INDIAN TRIBAL CANCER PATIENTS

The management of cancer disease can have a major impact on every aspect of a patient's Quality of Life (Q.O.L.). This paper presents an application of Multi Criteria Futuristic Decision Making (M.C.F.D.M.) Methodology to generate futuristic priorities and to select optimal futuristic priority scenario for enhancing the Quality of Life of Indian Tribal Cancer Population