The Accuracy of Non‐traditional versus Traditional Methods of Forecasting Lumpy Demand

Forecasting for inventory items with lumpy demand is difficult because of infrequent nonzero demands with high variability. This article developed two methods to forecast lumpy demand: an optimally weighted moving average method and an intelligent pattern‐seeking method. We compare them with a number of well‐referenced methods typically applied over the last 30 years in forecasting intermittent or lumpy demand. The comparison is conducted over about 200,000 forecasts (using 1‐day‐ahead and 5‐day‐ahead review periods) for 24 series of actual product demands across four different error measures. One of the most important findings of our study is that the two non‐traditional methods perform better overall than the traditional methods. We summarize results and discuss managerial implications. Copyright © 2011 John Wiley & Sons, Ltd.     

Minimal chromosome number in false spider mites (Tenuipalpidae)

Zusammenfassung Es wurde bei 3Brevipalpus-Arten mit thelytoker Reproduktion festgestellt, dass Zellen in embryonalem Gewebe nur zwei Chromosomen haben und vermutlich ein einfaches Chromosom-Komplement darstellen (n=1).     

Das apolaritäre Prinzip der Mittelfrequenz-Reizung

Ohne Zusammenfassung     

Further studies on endothelial cells of vertebrates and the problem of endothelial granules

Resumen Se describe la ultraestructura de células endoteliales de aorta abdominal de murciélago, foca y pinguino y se discuten los resultados en función de estudios precedentes nuestros y de otros autores sobre esas células en differentes especies. La presencia, o ausencia, y frequencia de los gránulos citoplasmáticos en las células endoteliales en las especies estudiadas parecería la expressión de un proceso evolutivo a nivel de clases.     

Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture

Manipulation or non-physiological embryo culture environments can lead to defective fetal programming in livestock. Our demonstration of reduced fetal methylation and expression of ovine IGF2R suggests pre-implantation embryo procedures may be vulnerable to epigenetic alterations in imprinted genes. This highlights the potential benefits of epigenetic diagnostic screening in developing embryo procedures.     

SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction

The effective use of targeted therapy is highly dependent on the identification of responder patient populations. Loss of FBW7, which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast cancer, colon cancer and T-cell acute lymphoblastic leukaemia (T-ALL). In line with these genomic data, engineered deletion of Fbw7 in mouse T cells results in T-ALL, validating FBW7 as a T-ALL tumour suppressor. Determining the precise molecular mechanisms by which FBW7 exerts antitumour activity is an area of intensive investigation. These mechanisms are thought to relate in part to FBW7-mediated destruction of key proteins relevant to cancer, including Jun, Myc, cyclin E and notch 1 (ref. 9), all of which have oncoprotein activity and are overexpressed in various human cancers, including leukaemia. In addition to accelerating cell growth, overexpression of Jun, Myc or notch 1 can also induce programmed cell death. Thus, considerable uncertainty surrounds how FBW7-deficient cells evade cell death in the setting of upregulated Jun, Myc and/or notch 1. Here we show that the E3 ubiquitin ligase SCF(FBW7) (a SKP1-cullin-1-F-box complex that contains FBW7 as the F-box protein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylation and destruction in a manner that depends on phosphorylation by glycogen synthase kinase 3. Human T-ALL cell lines showed a close relationship between FBW7 loss and MCL1 overexpression. Correspondingly, T-ALL cell lines with defective FBW7 are particularly sensitive to the multi-kinase inhibitor sorafenib but resistant to the BCL2 antagonist ABT-737. On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mechanism that enables FBW7-deficient cells to evade apoptosis. Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7-deficient T-ALL.