Impact of economic inventory and payment policies on working capital optimization in purchase-to-pay processes

The thesis at hand includes eight chapter and is structured as follows: Following a brief introduction of the topic in Chapter 1, Chapter 2 provides a survey of literature reviews in the area of lot sizing. Its intention is to show which streams of research emerged from Harris' seminal lot size model, and which major achievements have been accomplished in the respective areas. It first develops the methodology and then descriptively analyzes the sample. Subsequently, a content-related classification scheme for lot sizing models is developed, and the reviews contained in the sample are discussed in light of this classification scheme. The analysis reveals that various extensions of Harris' lot size model have been developed over the years, such as lot sizing models that include multi-stage inventory systems, incentives, or productivity issues. The aims of such a tertiary study are the following: firstly, it helps primary researchers to position their own work in the literature, to reproduce the development of different types of lot sizing problems, and to find starting points if they intend to work in a new research direction. Secondly, the study identifies several topics that offer opportunities for future secondary research apart from the ones covered in this thesis. In the presence of a progressive payment scheme, the supplier offers a sequence of credit periods, where the interest rate that is charged on the outstanding balance usually increases from period to period. If a buyer faces a progressive trade credit scheme, various options for settling the unpaid balance exist, where the financial impact of each option depends on the current credit interest structure and the alternative investment conditions. Chapter 3 takes up this issue by generalizing the trade credit inventory model with progressive interest scheme by considering a) the case where the credit interest rate of the buyer may (but not necessarily has to) exceed the interest rate charged by the supplier, b) where the buyer has the option to settle the outstanding balance continuously within the credit periods, c) where compound interest accrues at the retailer, and d) bank loans are available as a substitute for the trade credit. In addition, some inaccuracies in earlier formulations of the effective interest cost are corrected. Subsequently, Chapter 4 studies and extends solution algorithms for deriving the optimal ordering and payment policies of a retailer on the condition that the supplier provides a progressive interest scheme. Based on the finding that the piecewise total cost functions are convex but not necessarily continuous, a modified solution algorithm is developed and collated with existing ones in the course of a simulation experiment. The results indicate that the modified algorithm can locate all optimal solutions and outperforms existing approaches. Chapters 5 and 6 further extend the scope of the analysis by considering models aimed at finding ordering and payment policies for a buyer with stock-dependent demand and a supplier that offers a progressive payment scheme. Such a setting can frequently be observed in retail stores where the demand rate is usually influenced by the amount of inventories displayed on the shelves. These chapters correct some errors in the formulation of previously published approaches and extend those works by assuming that the credit interest rate of the retailer may exceed the interest rate charged by the supplier. Several numerical examples illustrate the benefits of the suggested modifications. The results also illustrate the close linkage between operational and financial aspects in supply chain management, which should be considered by employing more integrated planning approaches. As decisions on the working capital structure of the company defined by an appropriate inventory and payment policy significantly influence future cash-flows and thus the temporal allocation of payments, they should also be evaluated in terms of long-term profitability by considering their net present value or equivalent measures. Especially in situations where trade credit agreements are used over a long period of time and where discount rates are varying, explicitly considering the time-value of money in inventory models helps to make them more realistic. This aspect is considered in Chapter 7 that studies the optimal ordering and payment policies of a buyer assuming that the supplier offers a progressive interest scheme. The models proposed enable decision makers to improve decision making and the results reveal that taking into account the temporal allocation of payments, the prevailing interest relation influences replenishment policies significantly. Finally, Chapter 8 studies a buyer sourcing a product from multiple suppliers under stochastic demand. The buyer uses a (Q,s) continuous review, reorder point, order quantity inventory control system to determine the size and timing of orders. Lead time is assumed to be deterministic and to vary linearly with the lot size, wherefore lead time and the associated stock-out risk may be influenced both by varying the lot size and the number of contracted suppliers. After presenting several mathematical models for a multiple supplier single buyer integrated inventory problem with stochastic demand and variable lead time, the impact of different delivery structures on the risk of incurring a stock-out during lead time and the required inventories is analyzed

Chronic Immune Activation in HIV-1 Infection Contributes to Reduced Interferon Alpha Production via Enhanced CD40:CD40 Ligand Interaction

Although a signature of increased interferon (IFN-)alpha production is observed in HIV-1 infection, the response of circulating plasmacytoid dendritic cells (PDC) to Toll-like receptor ligand stimulation is substantially impaired. This functional PDC deficit, which we specifically observed in HIV-1 infected individuals with less than 500 CD4+ T cells/µl, is not well understood. We provide evidence that the peripheral IFN-alpha production in HIV-1 infection is actively suppressed by the enhanced interaction of CD40 ligand (CD40L), a member of the tumor necrosis factor family, and its receptor CD40, which are both upregulated upon immune activation. Plasma levels of soluble CD40L were significantly higher in untreated HIV-1 infected individuals (n = 52) than in subjects on long-term antiretroviral therapy (n = 62, p<0.03) and in uninfected control donors (n = 16, p<0.001). Concomitantly, cell-associated CD40L and the expression of the receptor CD40 on the PDC were significantly upregulated in HIV-1 infection (p<0.05). Soluble and cell-associated CD40L inhibited the PDC-derived IFN-alpha production by CpG oligodeoxynucleotides dose-dependently. This suppressive effect was observed at much lower, physiological CD40L concentrations in peripheral blood mononuclear cells (PBMC) of HIV-1 infected individuals compared to controls (p<0.05). The CpG-induced IFN-alpha production in PBMC of HIV-1 infected donors was directly correlated with PDC and CD4+ T cell counts, and inversely correlated with the viral loads (p<0.001). In HIV-1 infected donors with less than 500 CD4+ T cells/µl, the CpG-induced IFN-alpha production was significantly correlated with the percentage of CD40-expressing PDC and the level of CD40 expression on these cells (p<0.05), whereas CD40L plasma levels played a minor role. In addition, low-dose CD40L contributed to the enhanced production of interleukin 6 and 8 in PBMC of HIV-1 infected donors compared to controls. Our data support the conclusion that the chronic immune activation in HIV-1 infection impairs peripheral PDC innate immune responses at least in part via enhanced CD40:CD40L interactions

Tensin3 Is a Negative Regulator of Cell Migration and All Four Tensin Family Members Are Downregulated in Human Kidney Cancer

BACKGROUND: The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4) are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC), as well as probed the biological function of Tensin3. PRINCIPAL FINDINGS: Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated in human kidney tumors (50-100% reduction versus normal kidney cortex; P<0.001). Furthermore, the mRNA expressions of Tensins mostly correlated positively with each other and negatively with tumor grade, but not tumor size. Immunohistochemical analysis revealed Tensin3 to be present in the cytoplasm of tubular epithelium in normal human kidney sections, whilst expression was weaker or absent in 41% of kidney tumors. A subset of tumor sections showed a preferential plasma membrane expression of Tensin3, which in clear cell RCC patients was correlated with longer survival. Stable expression of Tensin3 in HEK 293 cells markedly inhibited both cell migration and matrix invasion, a function independent of putative phosphatase activity in Tensin3. Conversely, siRNA knockdown of endogenous Tensin3 in human cancer cells significantly increased their migration. CONCLUSIONS: Our findings indicate that the Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. Moreover, tumorigenesis in the human kidney may be facilitated by a general downregulation of Tensins. Therefore, anti-metastatic therapies may benefit from restoring or preserving Tensin expression in primary tumors

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Publisher Copyright: © 2021, The Author(s).Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.Peer reviewe

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

Impact of economic inventory and payment policies on working capital optimization in purchase-to-pay processes

The thesis at hand includes eight chapter and is structured as follows: Following a brief introduction of the topic in Chapter 1, Chapter 2 provides a survey of literature reviews in the area of lot sizing. Its intention is to show which streams of research emerged from Harris' seminal lot size model, and which major achievements have been accomplished in the respective areas. It first develops the methodology and then descriptively analyzes the sample. Subsequently, a content-related classification scheme for lot sizing models is developed, and the reviews contained in the sample are discussed in light of this classification scheme. The analysis reveals that various extensions of Harris' lot size model have been developed over the years, such as lot sizing models that include multi-stage inventory systems, incentives, or productivity issues. The aims of such a tertiary study are the following: firstly, it helps primary researchers to position their own work in the literature, to reproduce the development of different types of lot sizing problems, and to find starting points if they intend to work in a new research direction. Secondly, the study identifies several topics that offer opportunities for future secondary research apart from the ones covered in this thesis. In the presence of a progressive payment scheme, the supplier offers a sequence of credit periods, where the interest rate that is charged on the outstanding balance usually increases from period to period. If a buyer faces a progressive trade credit scheme, various options for settling the unpaid balance exist, where the financial impact of each option depends on the current credit interest structure and the alternative investment conditions. Chapter 3 takes up this issue by generalizing the trade credit inventory model with progressive interest scheme by considering a) the case where the credit interest rate of the buyer may (but not necessarily has to) exceed the interest rate charged by the supplier, b) where the buyer has the option to settle the outstanding balance continuously within the credit periods, c) where compound interest accrues at the retailer, and d) bank loans are available as a substitute for the trade credit. In addition, some inaccuracies in earlier formulations of the effective interest cost are corrected. Subsequently, Chapter 4 studies and extends solution algorithms for deriving the optimal ordering and payment policies of a retailer on the condition that the supplier provides a progressive interest scheme. Based on the finding that the piecewise total cost functions are convex but not necessarily continuous, a modified solution algorithm is developed and collated with existing ones in the course of a simulation experiment. The results indicate that the modified algorithm can locate all optimal solutions and outperforms existing approaches. Chapters 5 and 6 further extend the scope of the analysis by considering models aimed at finding ordering and payment policies for a buyer with stock-dependent demand and a supplier that offers a progressive payment scheme. Such a setting can frequently be observed in retail stores where the demand rate is usually influenced by the amount of inventories displayed on the shelves. These chapters correct some errors in the formulation of previously published approaches and extend those works by assuming that the credit interest rate of the retailer may exceed the interest rate charged by the supplier. Several numerical examples illustrate the benefits of the suggested modifications. The results also illustrate the close linkage between operational and financial aspects in supply chain management, which should be considered by employing more integrated planning approaches. As decisions on the working capital structure of the company defined by an appropriate inventory and payment policy significantly influence future cash-flows and thus the temporal allocation of payments, they should also be evaluated in terms of long-term profitability by considering their net present value or equivalent measures. Especially in situations where trade credit agreements are used over a long period of time and where discount rates are varying, explicitly considering the time-value of money in inventory models helps to make them more realistic. This aspect is considered in Chapter 7 that studies the optimal ordering and payment policies of a buyer assuming that the supplier offers a progressive interest scheme. The models proposed enable decision makers to improve decision making and the results reveal that taking into account the temporal allocation of payments, the prevailing interest relation influences replenishment policies significantly. Finally, Chapter 8 studies a buyer sourcing a product from multiple suppliers under stochastic demand. The buyer uses a (Q,s) continuous review, reorder point, order quantity inventory control system to determine the size and timing of orders. Lead time is assumed to be deterministic and to vary linearly with the lot size, wherefore lead time and the associated stock-out risk may be influenced both by varying the lot size and the number of contracted suppliers. After presenting several mathematical models for a multiple supplier single buyer integrated inventory problem with stochastic demand and variable lead time, the impact of different delivery structures on the risk of incurring a stock-out during lead time and the required inventories is analyzed

Correlation of CpG-induced interferon (IFN)-alpha production with clinical parameters.

<p>Spearman rank order correlation of CpG-A and CpG-P induced IFN-alpha production with (<b>a</b>) the percentage of PDC, (<b>b</b>) the CD4+ T cell count, and (<b>c</b>) the viral load in untreated HIV-1 infected individuals (n = 40).</p

Suppression of interferon (IFN) alpha production by CD40 ligand.

<p>(<b>a</b>) Preincubation of peripheral blood mononuclear cells (PBMC) of controls without (w/o) or with (w/t) a cell-culture grade commercial soluble CD40 ligand (sCD40L; 3 µg/ml) for 48 hours (h), followed by stimulation with CpG-P 21798. Data represent 11 and 5 separate experiments for IL-3 levels of 0 and 5–5,000 pg/ml, respectively. The arrow indicates physiological IL-3 levels. (<b>b</b>) Neutralization of sCD40L with a cell-culture grade anti-CD40L antibody with subsequent CpG-P stimulation in two donors. Similar data were obtained using CpG-A (data not shown). (<b>c</b>) Direct effect of sCD40L (3 µg/ml) on the CpG-P induced IFN-alpha production by plasmacytoid dendritic cells (PDC) of control donors. (<b>d</b>) Expression of cell-associated CD40L (cCD40L) on baby hamster kidney (BHK) cells. (<b>e</b>) Shedding of sCD40L into the cell culture supernatants after 24 h and 48 h of culture. (<b>f</b>) Western Blot of concentrated supernatants of CD40L-expressing BHK cells and a commercial sCD40L preparation (R&D Systems) using reducing conditions. Data represent three separate experiments. No bands were detected in the supernatants of BHK wild type cells (data not shown). (<b>g</b>) Inhibition of CpG-P induced IFN-alpha production using sCD40L from R&D Systems and BHK cells. Statistics were calculated between PBMC of HIV-1 infected patients (pat.) (n = 5) and controls (ctrl.) (n = 10) exposed to sCD40L (R&D Systems). (<b>h</b>) cCD40L expression on CD4+ and CD8+ T cells of control donors after stimulation with mock (grey filled curve) or PMA/ionomycin (black dotted curve). (<b>i</b>) Inhibition of CpG-P induced IFN-alpha production by increasing counts of untreated (unstim.) or PMA/ionomycin-stimulated (stim.) CD4+ T cells, which were left unfixed or fixed used 4% paraformaldehyde, and coincubated with 1×10⁶ PBMC of five control donors. Similar results were obtained with CpG-A (data not shown). (<b>j</b>) Inhibition of CpG-P induced IFN-alpha production by paraformaldehyde-fixed cCD40L-expressing and wild type (WT) BHK cells using PBMC of eight control donors. Data are presented as mean and standard error. *p<0.05, **p<0.01, ***p<0.001 (Student's t-test).</p