Intermittent demand forecasting in the Enterprise: Empirical verification

Forecasting methods are often valued by means of simulation studies. For intermittent demand items there are often very few non–zero observations, so it is hard to check any assumptions, because statistical information is often too weak to determine, for example, distribution of a variable. Therefore, it seems important to verify the forecasting methods on the basis of real data. The main aim of the article is an empirical verification of several forecasting methods applicable in case of intermittent demand. Some items are sold only in specific subperiods (in given month in each year, for example), but most forecasting methods (such as Croston's method) give non–zero forecasts for all periods. For example, summer work clothes should have non–zero forecasts only for summer months and many methods will usually provide non–zero forecasts for all months under consideration. This was the motivation for proposing and testing a new forecasting technique which can be applicable to seasonal items. In the article six methods were applied to construct separate forecasting systems: Croston's, SBA (Syntetos–Boylan Approximation), TSB (Teunter, Syntetos, Babai), MA (Moving Average), SES (Simple Exponential Smoothing) and SESAP (Simple Exponential Smoothing for Analogous subPeriods). The latter method (SESAP) is an author's proposal dedicated for companies facing the problem of seasonal items. By analogous subperiods the same subperiods in each year are understood, for example, the same months in each year. A data set from the real company was used to apply all the above forecasting procedures. That data set contained monthly time series for about nine thousand products. The forecasts accuracy was tested by means of both parametric and non–parametric measures. The scaled mean and the scaled root mean squared error were used to check biasedness and efficiency. Also, the mean absolute scaled error and the shares of best forecasts were estimated. The general conclusion is that in the analyzed company a forecasting system should be based on two forecasting methods: TSB and SESAP, but the latter method should be applied only to seasonal items (products sold only in specific subperiods). It also turned out that Croston's and SBA methods work worse than much simpler methods, such as SES or MA. The presented analysis might be helpful for enterprises facing the problem of forecasting intermittent items (and seasonal intermittent items as well).     

RNA-mediated epigenetic programming of a genome-rearrangement pathway

Genome-wide DNA rearrangements occur in many eukaryotes but are most exaggerated in ciliates, making them ideal model systems for epigenetic phenomena. During development of the somatic macronucleus, Oxytricha trifallax destroys 95% of its germ line, severely fragmenting its chromosomes, and then unscrambles hundreds of thousands of remaining fragments by permutation or inversion. Here we demonstrate that DNA or RNA templates can orchestrate these genome rearrangements in Oxytricha, supporting an epigenetic model for sequence-dependent comparison between germline and somatic genomes. A complete RNA cache of the maternal somatic genome may be available at a specific stage during development to provide a template for correct and precise DNA rearrangement. We show the existence of maternal RNA templates that could guide DNA assembly, and that disruption of specific RNA molecules disables rearrangement of the corresponding gene. Injection of artificial templates reprogrammes the DNA rearrangement pathway, suggesting that RNA molecules guide genome rearrangement.     

Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia

The duplication of entire genomes has long been recognized as having great potential for evolutionary novelties, but the mechanisms underlying their resolution through gene loss are poorly understood. Here we show that in the unicellular eukaryote Paramecium tetraurelia, a ciliate, most of the nearly 40,000 genes arose through at least three successive whole-genome duplications. Phylogenetic analysis indicates that the most recent duplication coincides with an explosion of speciation events that gave rise to the P. aurelia complex of 15 sibling species. We observed that gene loss occurs over a long timescale, not as an initial massive event. Genes from the same metabolic pathway or protein complex have common patterns of gene loss, and highly expressed genes are over-retained after all duplications. The conclusion of this analysis is that many genes are maintained after whole-genome duplication not because of functional innovation but because of gene dosage constraints.     

Role of Bax and Bak in mitochondrial morphogenesis

Bcl-2 family proteins are potent regulators of programmed cell death. Although their intracellular localization to mitochondria and the endoplasmic reticulum has focused research on these organelles, how they function remains unknown. Two members of the Bcl-2 family, Bax and Bak, change intracellular location early in the promotion of apoptosis to concentrate in focal clusters at sites of mitochondrial division. Here we report that in healthy cells Bax or Bak is required for normal fusion of mitochondria into elongated tubules. Bax seems to induce mitochondrial fusion by activating assembly of the large GTPase Mfn2 and changing its submitochondrial distribution and membrane mobility-properties that correlate with different GTP-bound states of Mfn2. Our results show that Bax and Bak regulate mitochondrial dynamics in healthy cells and indicate that Bcl-2 family members may also regulate apoptosis through organelle morphogenesis machineries.     

Translational control of intron splicing in eukaryotes

Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poorly understood. In most organisms, short introns recognized by the intron definition mechanism cannot be efficiently predicted solely on the basis of sequence motifs. In multicellular eukaryotes, long introns are recognized through exon definition and most genes produce multiple mRNA variants through alternative splicing. The nonsense-mediated mRNA decay (NMD) pathway may further shape the observed sets of variants by selectively degrading those containing premature termination codons, which are frequently produced in mammals. Here we show that the tiny introns of the ciliate Paramecium tetraurelia are under strong selective pressure to cause premature termination of mRNA translation in the event of intron retention, and that the same bias is observed among the short introns of plants, fungi and animals. By knocking down the two P. tetraurelia genes encoding UPF1, a protein that is crucial in NMD, we show that the intrinsic efficiency of splicing varies widely among introns and that NMD activity can significantly reduce the fraction of unspliced mRNAs. The results suggest that, independently of alternative splicing, species with large intron numbers universally rely on NMD to compensate for suboptimal splicing efficiency and accuracy.     

Biology and defensive secretion of myrmecophilous Thiasophila spp. (Coleoptera: Staphylinidae: Aleocharinae) associated with the Formica rufa species group

Various aspects of the biology of the myrmecophilous Thiasophila angulata and T. szujeckii (Staphylinidae; Aleocharinae), mainly associated with the Formica rufa species group, are studied. The composition of defensive gland secretions from adults of T. angulata has been analysed. The complete development (egg-L_1-3-pupa-adult form), including adult overwintering, of both species takes place solely in ant nests. Under laboratory conditions, this lasts for about 22 days in T. angulata, and the period elapsing between the old and new generations of insects is approximately two months. The mean fecundity of adults of this species (28 eggs) was determined, as well as the duration of its reproductive period (mean 28.5 days), and lifespan (mean 67 days). In natural conditions T. angulata, found within nests of Formica polyctena and F. rufa, produces three generations, and the sibling species T. szujeckii one generation per year. These two species differ in their phenologies and abundance dynamics of adults and larvae, which is linked to the size and temperature regime of the host nest. The results of this study uphold the recent separation of T. angulata and T. szujeckii based on morphological features of adults and selected molecular markers. Adults and larvae of T. angulata forage on both live and dead food items accumulated by the host, as well as on the host’s eggs and larvae. Both the beetle larvae and adults remain unmolested among the host workers. The adults use their defensive gland secretions, which contains substantial quantities of toxic quinones, when necessary. According to the current categories of myrmecophiles, T. angulata (and by analogy, T. szujeckii as well) should be classified as a species wholly integrated with the host.     

Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation

The optic atrophy 3 (OPA3) gene, which has no known homolog or biological function, is mutated in patients with hereditary optic neuropathies. Here, we identified OPA3 as an integral protein of the mitochondrial outer membrane (MOM), with a C-terminus exposed to the cytosol and an N-terminal mitochondrial targeting domain. By quantitative analysis, we demonstrated that overexpression of OPA3 significantly induced mitochondrial fragmentation, whereas OPA3 knockdown resulted in highly elongated mitochondria. Cells with mitochondria fragmented by OPA3 did not undergo spontaneous apoptotic cell death, but were significantly sensitized to staurosporine- and TRAIL-induced apoptosis. In contrast, overexpression of a familial OPA3 mutant (G93S) induced mitochondrial fragmentation and spontaneous apoptosis, suggesting that OPA3 mutations may cause optic atrophy via a gain-of-function mechanism. Together, these results indicate that OPA3, as an integral MOM protein, has a crucial role in mitochondrial fission, and provides a direct link between mitochondrial morphology and optic atrophy.     

"Every Man in His Notions" or Alchemists' Discussion on Artificial Intelligence

A survey of the main approaches in a mind study -oriented part of Artificial Intelligence is made focusing on controversial issues and extreme hypotheses. Various meanings of terms: "intelligence" and "artificial intelligence" are discussed. Limitations for constructing intelligent systems resulting from the lack of formalized models of cognitive activity are shown. The approaches surveyed are then recapitulated in the light of these limitations.     

Watching hydrogen-bond dynamics in a beta-turn by transient two-dimensional infrared spectroscopy

X-ray crystallography and nuclear magnetic resonance measurements provide us with atomically resolved structures of an ever-growing number of biomolecules. These static structural snapshots are important to our understanding of biomolecular function, but real biomolecules are dynamic entities that often exploit conformational changes and transient molecular interactions to perform their tasks. Nuclear magnetic resonance methods can follow such structural changes, but only on millisecond timescales under non-equilibrium conditions. Time-resolved X-ray crystallography has recently been used to monitor the photodissociation of CO from myoglobin on a subnanosecond timescale, yet remains challenging to apply more widely. In contrast, two-dimensional infrared spectroscopy, which maps vibrational coupling between molecular groups and hence their relative positions and orientations, is now routinely used to study equilibrium processes on picosecond timescales. Here we show that the extension of this method into the non-equilibrium regime allows us to observe in real time in a short peptide the weakening of an intramolecular hydrogen bond and concomitant opening of a beta-turn. We find that the rate of this process is two orders of magnitude faster than the 'folding speed limit' established for contact formation between protein side chains.