A simulated annealing approach to optimal storing in a multi-level warehouse

We propose a simulated annealing algorithm specifically tailored to optimise total retrieval times in a multi-level warehouse under complex pre-batched picking constraints. Experiments on real data from a picker-to-parts order picking process in the warehouse of a European manufacturer show that optimal storage assignments do not necessarily display features presumed in heuristics, such as clustering of positively correlated items or ordering of items by picking frequency. In an experiment run on more than 4000 batched orders with 1 to 150 items per batch, the storage assignment suggested by the algorithm produces a 21\% reduction in the total retrieval time with respect to a frequency-based storage assignment

Concept of dealing with uncertainty in radar-based data for hydrological purpose

International audiencePrecipitation radar-based data constitute essential input to Numerical Weather Prediction (NWP) and rainfall-runoff models, however the data introduce a number of errors. Thus their uncertainty should be determined to provide end-users with more reliable information about forecasts. The common idea is to use Quality Index (QI) scheme for some number of quality parameters on the assumption that: (1) relationship between the parameters and relevant quality indexes is linear; (2) averaged QI is a weighted average of all particular indexes. The uncertainty parameters can be topography-dependent, resulting from spatial and temporal distribution of data, etc. Uncertainty in radar-based data is described by gamma PDF of precipitation, and it is proposed to determine the probability density function (PDF) parameters basing on QI values. Practically, precipitation is presented as ensemble of quantiles of the PDF and such an ensemble can constitute input to rainfall-runoff modelling. Since the ensemble is a precipitation input, the hydrological model needs to be activated according to a number of input members

Long-term multi-source precipitation estimation with high resolution (RainGRS Clim)

This paper explores the possibility of using multi-source precipitation estimates for climatological applications. A data-processing algorithm (RainGRS Clim) has been developed to work on precipitation accumulations such as daily or monthly totals, which are significantly longer than operational accumulations (generally between 5 min and 1 h). The algorithm makes the most of additional opportunities, such as the possibility of complementing data with delayed data, access to high-quality data that are not operationally available, and the greater efficiency of the algorithms for data quality control and merging with longer accumulations. Verification of the developed algorithms was carried out using monthly accumulations through comparison with precipitation from manual rain gauges. As a result, monthly accumulations estimated by RainGRS Clim were found to be significantly more reliable than accumulations generated operationally. This improvement is particularly noticeable for the winter months, when precipitation estimation is much more difficult due to less reliable radar estimates.</p

26 Efekty uboczne kompleksowej raodioterapii u chorych na nowotwory narządów płciowych

Radioterapia jest jedną z podstawowych metod leczenia onkologicznego w raku szyjki i błony śluzowej macicy. Ze względu na różną radiowrażliwość narządów miednicy mniejszej autorzy pracy zwrócili szczególną uwagę na ewentualną obecność objawów uszkodzenia przewodu pokarmowego, układu moczowego i szpiku kostnego.W okresie 1998–2000 w Klinice Ginekologii Operacyjnej poddano obserwacji 40 chorych poddanych kompleksowej radioterapii. Wszystkie pacjentki w trakcie teleterapii otrzymały całkowitą dawkę 28 Gy na guz w okresie 4 tygodni oraz poddane zostały brachyterapii. W zależności od stopnia zaawansowania klinicznego nowotworu zastosowano:-u 25 chorych ze stopniem klinicznym nowotworu I i II – brachyterapię dopochwową w dawce 24 Gy (w 3 cotygodniowych frakcjach);-u 15 chorych ze stopniem zaawansowania II, III i IV – brachyterapię domaciczną w dawce 40 Gy (w 5 cotygodniowych frakcjach).Brachyterapię stosowano za pomocą microSelectronu HDR firmy Nucletron z użyciem żródła irydowego Ir192 z nominalną aktywnością 10 Ci (370GBq).Zaobserwowano:[[tgroup cols="3"]][[colspec colname="col1"/]][[colspec colname="col2"/]][[colspec colname="col3"/]][[tbody]][[row]][[entry align="left"]]1. Objawy uszkodzenia przewodu pokarmowego:[[/entry]][[entry align="left"]]nudności i wymioty[[/entry]][[entry align="left"]]− 4(10%)[[/entry]][[/row]][[row]][[entry/]][[entry align="left"]]biegunka[[/entry]][[entry align="left"]]− 6(15%)[[/entry]][[/row]][[row]][[entry align="left"]]2. Objawy podrażnienia układu moczowego (objawy dyzuryczne + zmiany w badaniu ogó1nym moczu):[[/entry]][[entry/]][[entry align="left"]]− 22 (55%)[[/entry]][[/row]][[row]][[entry align="left"]]3. Objawy uszkodzenia szpiku kostnego:[[/entry]][[entry align="left"]]niedokrwistość :[[/entry]][[entry align="left"]]− 3 (7,5%)[[/entry]][[/row]][[row]][[entry/]][[entry align="left"]]leukopenia:[[/entry]][[entry align="left"]]− 9 (22,5%)[[/entry]][[/row]][[/tbody]][[/tgroup]]Uzyskane wyniki potwierdzają względnie niski odsetek notowanych powikłań. Jest to dowodem na to, że tylko właściwa ocena kliniczna i prawidłowo prowadzona dozymetria przy kompleksowej radioterapii umożliwiają minimalizację objawów ubocznych

Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes

Enteroviral infections have been associated with the development of type 1 diabetes (T1D), a chronic inflammatory disease characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Cultured human islets, including the insulin-producing beta cells, can be infected with coxsackievirus B4 (CVB4) and thus are useful for understanding cellular responses to infection. We performed quantitative mass spectrometry analysis on cultured primary human islets infected with CVB4 to identify molecules and pathways altered upon infection. Corresponding uninfected controls were included in the study for comparative protein expression analyses. Proteins were significantly and differentially regulated in human islets challenged with virus compared with their uninfected counterparts. Complementary analyses of gene transcripts in CVB4-infected primary islets over a time course validated the induction of RNA transcripts for many of the proteins that were increased in the proteomics studies. Notably, infection with CVB4 results in a considerable decrease in insulin. Genes/proteins modulated during CVB4 infection also include those involved in activation of immune responses, including type I interferon pathways linked to T1D pathogenesis and with antiviral, cell repair, and inflammatory properties. Our study applies proteomics analyses to cultured human islets challenged with virus and identifies target proteins that could be useful in T1D interventions

Artificially expanded genetic information system: a new base pair with an alternative hydrogen bonding pattern

To support efforts to develop a ‘synthetic biology’ based on an artificially expanded genetic information system (AEGIS), we have developed a route to two components of a non-standard nucleobase pair, the pyrimidine analog 6-amino-5-nitro-3-(1′-β-D-2′-deoxyribofuranosyl)-2(1H)-pyridone (dZ) and its Watson–Crick complement, the purine analog 2-amino-8-(1′-β-D-2′-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (dP). These implement the pyDDA:puAAD hydrogen bonding pattern (where ‘py’ indicates a pyrimidine analog and ‘pu’ indicates a purine analog, while A and D indicate the hydrogen bonding patterns of acceptor and donor groups presented to the complementary nucleobases, from the major to the minor groove). Also described is the synthesis of the triphosphates and protected phosphoramidites of these two nucleosides. We also describe the use of the protected phosphoramidites to synthesize DNA oligonucleotides containing these AEGIS components, verify the absence of epimerization of dZ in those oligonucleotides, and report some hybridization properties of the dZ:dP nucleobase pair, which is rather strong, and the ability of each to effectively discriminate against mismatches in short duplex DNA

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

Proteomic and Transcriptional Profiles of Human Stem Cell-Derived beta Cells Following Enteroviral Challenge

Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant beta-cell stress and damage occur with viral infection, leading to cells that are dysfunctional and vulnerable to destruction. Human stem cell-derived beta (SC-beta) cells are insulin-producing cell clusters that closely resemble native beta cells. To better understand the events precipitated by enteroviral infection of beta cells, we investigated transcriptional and proteomic changes in SC-beta cells challenged with coxsackie B virus (CVB). We confirmed infection by demonstrating that viral protein colocalized with insulin-positive SC-beta cells by immunostaining. Transcriptome analysis showed a decrease in insulin gene expression following infection, and combined transcriptional and proteomic analysis revealed activation of innate immune pathways, including type I interferon (IFN), IFN-stimulated genes, nuclear factor-kappa B (NF-kappaB) and downstream inflammatory cytokines, and major histocompatibility complex (MHC) class I. Finally, insulin release by CVB4-infected SC-beta cells was impaired. These transcriptional, proteomic, and functional findings are in agreement with responses in primary human islets infected with CVB ex vivo. Human SC-beta cells may serve as a surrogate for primary human islets in virus-induced diabetes models. Because human SC-beta cells are more genetically tractable and accessible than primary islets, they may provide a preferred platform for investigating T1D pathogenesis and developing new treatments