Order batching in a bucket brigade order picking system considering picker blocking

Bucket brigade order picking improves operational productivity by balancing workloads among pickers with a minimal level of managerial planning and oversight. However, due to variability and uncertainty of the pick locations within a particular order or batch, pickers can encounter blocking delays and thus lose productivity. This study formulates a model to quantify blocking delays and develops a control model to reduce blocking in bucket brigade order picking systems. The Indexed Batching Model for Bucket brigades (IBMB) has indexed batching constraints for generating batch alternatives, bucket brigade picker blocking constraints for quantifying blocking delay, and release-time updating constraints for progressively connecting the batching results with blocking quantification. The IBMB minimizes total retrieval time and improves picker utilization from 2 to 9 % across diverse and practical order picking situations while maintaining the static Work-In-Process. We note that modeling the separation of retrieved batches into orders still remains a challenge.     

Gene context conservation of a higher order than operons

Operons, co-transcribed and co-regulated contiguous sets of genes, are poorly conserved over short periods of evolutionary time. The gene order, gene content and regulatory mechanisms of operons can be very different, even in closely related species. Here, we present several lines of evidence which suggest that, although an operon and its individual genes and regulatory structures are rearranged when comparing the genomes of different species, this rearrangement is a conservative process. Genomic rearrangements invariably maintain individual genes in very specific functional and regulatory contexts. We call this conserved context an uber-operon.     

Integration of image analysis and robotics into a fully automated colony picking and plate handling system.

We describe here the integration of image analysis and robotics to produce a fully automated colony picking/plate handling system. Biological tests were performed to verify its performance in terms of sterilisation and accuracy of picking. The machine was then used by a single operative to pick a 36,000 clone cDNA library in approximately 42 hrs over 5 days.     

乙型肝炎病毒B2和C2亚型中SSRs的比较分析

乙型肝炎病毒(hepatitis B virus,HBV)属于嗜肝DNA病毒科(hepadnaviridae),它分布在世界各地并严重危害人类的健康。本文从NCBI的GenBank中下载了106条B2亚型和130条C2亚型的基因组全长序列,以下载的数据为材料,分析简单重复序列(simple sequence repeats,SSRs)在B2和C2亚型基因组序列中的分布情况。结果显示,简单重复序列的重复次数比较少;二型简单重复序列在研究的五种简单重复序列类型中占绝对优势;这可能与B2和C2亚型基因组序列有较高的突变率有关。同时还发现最普遍的SSRs、序列间SSRs的平均相对丰度和平均相对密度在B2和C2亚型中分布情况相似。     

Mutations in the effector binding loops in the C2A and C2B domains of synaptotagmin I disrupt exocytosis in a nonadditive manner

The secretory vesicle protein synaptotagmin I (syt) plays a critical role in Ca2+-triggered exocytosis. Its cytoplasmic domain is composed of tandem C2 domains, C2A and C2B; each C2 domain binds Ca2+. Upon binding Ca2+, positively charged residues within the Ca2+-binding loops are thought to interact with negatively charged phospholipids in the target membrane to mediate docking of the cytoplasmic domain of syt onto lipid bilayers. The C2 domains of syt also interact with syntaxin and SNAP-25, two components of a conserved membrane fusion complex. Here, we have neutralized single positively charged residues at the membrane-binding interface of C2A (R233Q) and C2B (K366Q). Either of these mutations shifted the Ca2+ requirements for syt-liposome interactions from approximately 20 to approximately 40 microm Ca2+. Kinetic analysis revealed that the reduction in Ca2+-sensing activity was associated with a decrease in affinity for membranes. These mutations did not affect sytsyntaxin interactions but resulted in an approximately 50% loss in SNAP-25 binding activity, suggesting that these residues lie at an interface between membranes and SNAP-25. Expression of full-length versions of syt that harbored these mutations reduced the rate of exocytosis in PC12 cells. In both biochemical and functional assays, effects of the R233Q and K366Q mutations were not additive, indicating that mutations in one domain affect the activity of the adjacent domain. These findings indicate that the tandem C2 domains of syt cooperate with one another to trigger release via loop-mediated electrostatic interactions with effector molecules.     

The C2B domain of synaptotagmin I is a Ca2+-binding module

Synaptotagmin I is a synaptic vesicle protein that contains two C(2) domains and acts as a Ca(2+) sensor in neurotransmitter release. The Ca(2+)-binding properties of the synaptotagmin I C(2)A domain have been well characterized, but those of the C(2)B domain are unclear. The C(2)B domain was previously found to pull down synaptotagmin I from brain homogenates in a Ca(2+)-dependent manner, leading to an attractive model whereby Ca(2+)-dependent multimerization of synaptotagmin I via the C(2)B domain participates in fusion pore formation. However, contradictory results have been described in studies of Ca(2+)-dependent C(2)B domain dimerization, as well as in analyses of other C(2)B domain interactions. To shed light on these issues, the C(2)B domain has now been studied using biophysical techniques. The recombinant C(2)B domain expressed as a GST fusion protein and isolated by affinity chromatography contains tightly bound bacterial contaminants despite being electrophoretically pure. The contaminants bind to a polybasic sequence that has been previously implicated in several C(2)B domain interactions, including Ca(2+)-dependent dimerization. NMR experiments show that the pure recombinant C(2)B domain binds Ca(2+) directly but does not dimerize upon Ca(2+) binding. In contrast, a cytoplasmic fragment of native synaptotagmin I from brain homogenates, which includes the C(2)A and C(2)B domains, participates in a high molecular weight complex as a function of Ca(2+). These results show that the recombinant C(2)B domain of synaptotagmin I is a monomeric, autonomously folded Ca(2+)-binding module and suggest that a potential function of synaptotagmin I multimerization in fusion pore formation does not involve a direct interaction between C(2)B domains or requires a posttranslational modification.     

B cell immune repertoire diversifies in a predictable temporal order in vitro

The appearance of functional, antigen-specific B cells was studied in an in vitro fetal organ culture system in the absence of environmental influences associated with circulation and cell migration. In this way the B cell diversification process could be analyzed when genetic influences were dominating. By using this system in combination with the splenic focus assay, the frequency of developing B cells responsive to a number of hapten probes was measured. The results indicate that B cell diversification in vitro, in the apparent absence of many environmental influences, results in the appearance of antigen-responsive B cells in a predictable, temporal order. The results suggest that the acquisition of the expressed repertoire to a large extent is genetically controlled.     

DNA polymorphism of the C2 and factor B genes

Factor B and the second component of complement (C2) in man are encoded within the major histocompatibility complex by single loci that are less than 1 kb apart. A 2.3 kb factor B-specific cDNA probe has been used to examine, by Southern blot analysis, the genomic DNA of individuals typed for C2 and factor B by protein electrophoresis. We have identified a restriction fragment length polymorphism using the endonuclease Taq I, which subdivides haplotypes carrying both the common variant of C2 (C2C) and the fast (F) variant of factor B. This DNA polymorphism has been mapped to lie in the C2 gene and represents a new genetic marker not defined by protein electrophoresis. This polymorphism may serve as a useful marker in the genetic analysis of diseases that are related to the major histocompatibility complex.     

On the significance of C2, C4, and factor B polymorphisms in disease

Summary In this review article, recent evidence is presented that some diseases like insulin-dependent diabetes mellitus, multiple sclerosis, and idiopathic membranous nephropathy, which are primarily associated with HLA-D,DR, are also related to the rare C2, C4, and Factor B alleles. Circumstantial evidence is available that at least some of these rare variants may be functionally deficient. Based on the concept of functionally interacting gene clusters, mutant complement genes may lead to impaired effector mechanisms in virus neutralization or lysis of virus-infected cells. Other mechanisms such as alteration of vascular permeability may be involved in the development of proliferative retinopathy and familial hypertension. In lepromatous lepra, an impaired cell-mediated lysis of M. leprae may be related to the hemolytically inactive C4F1 allelic product.The authors' original work was supported in part by grants from Deutsche Forschungsgemeinschaft (Ri 164/14, Be 758/4, SFB 113, B3)     

Joint order batching and picker routing in single and multiple-cross-aisle warehouses using cluster-based tabu search algorithms

The organization of order picking operations is one of the most critical issues in warehouse management. In this paper, novel tabu search (TS) algorithms integrated with a novel clustering algorithm are proposed to solve the order batching and picker routing problems jointly for multiple-cross-aisle warehouse systems. A clustering algorithm that generates an initial solution for the TS algorithms is developed to provide fast and effective solutions to the order-batching problem. Unlike most common picker routing heuristics, we model the routing problem of pickers as a classical TSP and propose efficient Nearest Neighbor+Or-opt and Savings+2-Opt heuristics to meet the specific features for the problem. Various problem instances including the number of orders, weight of items, and picking coordinates are generated randomly, and detailed numerical experiments are carried out to evaluate the performances of the proposed methods. In conclusion, the TS algorithms come out to be the most efficient methods in terms of solution quality and computational efficiency.     

Structure and activation of complement components C2 and factor B

The activation of complement is initiated by two independent pathways. Each leads to the formation of a complex protease, C3 convertase, with equivalent specificity and function but different composition. The convertase derived from the classical pathway is composed of complement components C4 and C2 while that from the alternative pathway consists of components C3 and Factor B. C2 and Factor B contain the catalytic site of each convertase respectively. The amino acid sequence of Factor B has been determined. Limited sequence of CNBr-peptides isolated from C2 has also been obtained. The two enzymes are shown to be homologous and to represent a novel type of serine proteinase, characterized by their unusual structure and mechanism of activation, when compared to known serine proteinases.     

Synaptotagmin I-ΔC2B. A novel synaptotagmin isoform with a single C2 domain in the bovine adrenal medulla

Synaptotagmin I is a 65 kDa type 1 membrane glycoprotein found in secretory organelles that plays a key role in regulated exocytosis. We have characterised two forms (long and short) of synaptotagmin I that are present in the bovine adrenal medulla. The long form is a type I integral membrane protein which has two cytoplasmic C2 domains and corresponds to the previously characterised full-length synaptotagmin I isoform. The short-form synaptotagmin I-ΔC2B has the same structure in the lumenal and transmembrane sequences, but synaptotagmin I-ΔC2B is truncated such that it only has a single cytoplasmic C2 domain. Analysis of synaptotagmin I-ΔC2B expression indicates that synaptotagmin I-ΔC2B is preferentially expressed in the bovine adrenal medulla. However, it is absent from the dense core chromaffin granules. Furthermore, when expressed in the rat pheochromocytoma cell line PC12 bovine synaptotagmin I-ΔC2B is largely absent from dense core granules and synaptic-like microvesicles. Instead, indirect immunofluorescence microscopy reveals the intracellular location of synaptotagmin I-ΔC2B to be the plasma membrane.     

Transferases of O-antigen biosynthesis in Salmonella enterica: dideoxyhexosyltransferases of groups B and C2 and acetyltransferase of group C2.

The O antigen is a polymer of oligosaccharide units. O antigens differ in their sugar composition and glycosidic linkages, and genes responsible for O-antigen-specific biosynthesis are grouped in the rfb gene cluster. In this study, we identified two abequosyltransferase genes and an acetyltransferase gene in Salmonella enterica groups B and C2 by in vitro assay and identified paratosyl-, tyvelosyl-, and abequosyltransferase genes from S. enterica groups A and D and Yersinia pseudotuberculosis serovar IIA, respectively, by comparison.