A new physical accounting model for material flows in urban systems with application to the Stockholm Royal Seaport District

Sustainable urbanization requires streamlining of resource management in urban systems which in turn requires understanding of urban metabolism (UM). Even though various methods have been applied for UM analysis, to date there is no standardized method for comprehensive accounting of material flows in urban systems. Moreover, the accounting of material flows is rarely implemented with a bottom‐up approach that can provide a thorough analysis of UM. This article presents the Urban Accounting Model (UAM) which aims to allow comprehensive accounting of urban material flows based on a bottom‐up approach. The model comprises two interlinked sub‐models. The first was developed by integrating a new physical input output table (PIOT) framework for urban systems into a three‐dimensional structure. The second comprises a set of physical accounts for systematic accounting of material flows of each economic sector in the system in order to support the compilation of the PIOTs. The functions of the UAM were explored through its application to two urban neighborhoods in the Stockholm Royal Seaport district. The application highlighted that the UAM can describe the physical interactions between the urban system and the environment or other socioeconomic systems, and capture the intersectoral flows within the system. Moreover, its accounts provide information that allow an in‐depth analysis of the metabolism of specific sectors. Overall, the UAM can function as a useful tool for UM analysis as it systematizes data collection and at the same time depicts the physical reality of the urban system.     

Medium term planning of biopharmaceutical manufacture using mathematical programming

Regulatory pressures and capacity constraints are forcing the biopharmaceutical industry to consider employing multiproduct manufacturing facilities running on a campaign basis. The need for such flexible and cost-effective manufacture poses a significant challenge for planning and scheduling. This paper reviews the problem of planning and scheduling of biopharmaceutical manufacture and presents a methodology for the planning of multiproduct biopharmaceutical manufacturing facilities. The problem is formulated as a mixed integer linear program (MILP) to represent the relevant decisions required within the planning process and is tested on two typical biopharmaceutical industry planning problems. The proposed formulation is compared with an industrial rule based approach, which it outperforms in terms of profitability. The results indicate that the developed formulation offers an effective representation of the planning problem and would be a useful decision tool for manufacturers in the biopharmaceutical industry particularly at times of limited manufacturing capacity.     

Structural similarities and differences in Staphylococcus aureus exfoliative toxins A and B as revealed by their crystal structures

Staphylococcal aureus epidermolytic toxins (ETs) A and B are responsible for the induction of staphylococcal scalded skin syndrome, a disease of neonates and young children. The clinical features of this syndrome vary from localized blisters to severe exfoliation affecting most of the body surface. Comparison of the crystal structures of two subtypes of ETs-rETA (at 2.0 A resolution), rETB (at 2.8 A resolution), and an active site variant of rETA, Ser195Ala at 2.0 A resolution has demonstrated that their overall topology resembles that of a "trypsin-like" serine protease, but with significant differences at the N- and C-termini and loop regions. The details of the catalytic site in both ET structures are very similar to those in glutamate-specific serine proteases, suggesting a common catalytic mechanism. However, the "oxyanion hole," which is part of the catalytic sites of glutamate specific serine proteases, is in the closed or inactive conformation for rETA, yet in the open or active conformation for rETB. The ETs contain a unique amphipathic helix at the N-terminus, and it appears to be involved in optimizing the conformation of the catalytic site residues. Determination of the structure of the rETA catalytic site variant, Ser195Ala, showed no significant perturbation at the active site, establishing that the loss of biological and esterolytic activity can be attributed solely to disruption of the catalytic serine residue. Finally, the crystal structure of ETs, together with biochemical data and mutagenesis studies, strongly confirms the classification of these molecules as "serine proteases" rather than "superantigens."     

The DNase activity of an endoplasmic reticulum nuclease and its effect on DNA synthesis in vitro

An endoplasmic reticulum nuclease which was isolated previously in this laboratory from rat liver ( Kouidou et al. (1981) Eur.J. Bioch . 120, 9-14) was found to degrade linear and circular single stranded DNA but not double stranded DNA. The DNA fragments resulting from this cleavage were longer than 20 nucleotides. In addition the nuclease was found to improve the efficiency of DNA template used by DNA polymerase I in DNA synthesis in vitro. The results were the same whether incubation of the template with the nuclease was prior to addition of DNA polymerase I or simultaneously with polymerization. When nuclease was added after the completion of polymerization by DNA polymerase I it was ineffective unless the product was denatured. These data further corroborate the observation that double stranded DNA is not cleaved by this enzyme.     

On Characterizing Some Discrete Distributions by a Conditional Distribution and a Regression Function

In this paper we consider characterizations of the binomial, negative binomial, hypergeometric, negative hypergeometric, multinomial and multivariate hypergeometric distributions, by linear regression of one random variable (vector) on the other and the conditional distribution of the other random variable (vector) given the first. It is also indicated how these results can be used in genetics.     

Characterizations of Some Discrete Distribution Models Arising in Pollen Studies

Characterizations are obtained for multinomial and multiple binominal mixtures. Examples are given when the beta distribution is used as the mixing distribution. Biological applications are indicated.     

The Balkans and the colonization of Europe: the post‐glacial range expansion of the wild boar,Sus scrofa

Aim We focus on the biogeographical role of the Balkan Peninsula as a glacial refugium and source of northward post‐glacial dispersal for many European taxa. Specifically, we analysed the genetic structure and variation of wild boar (Sus scrofa) samples primarily from Greece, a region that has repeatedly served as a glacial refugium within the Balkan Peninsula. Location Continental Greece, the Aegean island of Samos and Bulgaria. Methods We analysed wild boar samples from 18 localities. Samples from common domestic breeds were also examined to take into account interactions between wild and domesticated animals. Phylogenetic analyses were carried out on a 637‐bp fragment of the mitochondrial DNA control region in 200 wild boar and 27 domestic pigs. The sequences were also compared with 791 Eurasian wild boar and domestic pig D‐loop sequences obtained from GenBank. Results Ninety‐four haplotypes were identified in the European wild boar data set, of which 68 were found in the Balkan samples and assigned to two previously described clades: the E1 European and Near Eastern clades. All of the continental samples clustered in the E1 clade and the samples from Samos fell into the Near Eastern clade, consistent with the island’s proximity to Asia Minor. Intriguingly, 62 novel haplotypes were identified and are found exclusively in the Balkans. Only six haplotypes were shared between wild boar and domestic pigs. Main conclusions Our data reveal numerous novel and geographically restricted haplotypes in wild boar populations, suggesting the presence of separate refugia in the Balkans. Our analyses support the hypothesis of a post‐glacial wild boar expansion consistent with the leading edge model, north and west from modern day Greece, and suggest little maternal introgression of Near Eastern and domestic haplotypes into wild Balkan populations.     

Let-7, Mir-98 and Mir-181 as Biomarkers for Cancer and Schizophrenia

Recent evidence supports a role of microRNAs in cancer and psychiatric disorders such as schizophrenia and bipolar disorder, through their regulatory role on the expression of multiple genes. The rather rare co-morbidity of cancer and schizophrenia is an old hypothesis which needs further research on microRNAs as molecules that might exert their oncosuppressive or oncogenic activity in the context of their role in psychiatric disorders. The expression pattern of a variety of different microRNAs was investigated in patients (N = 6) suffering from schizophrenia termed control, patients with a solid tumor (N = 10) and patients with both schizophrenia and tumor (N = 8). miRNA profiling was performed on whole blood samples using the miRCURY LNA microRNA Array technology (6th & 7th generation). A subset of 3 microRNAs showed a statistically significant differential expression between the control and the study groups. Specifically, significant down-regulation of the let-7p-5p, miR-98-5p and of miR-183-5p in the study groups (tumor alone and tumorand schizophrenia) was observed (p<0.05). The results of the present study showed that let-7, miR-98 and miR-183 may play an important oncosuppressive role through their regulatory impact in gene expression irrespective of the presence of schizophrenia, although a larger sample size is required to validate these results. Nevertheless, further studies are warranted in order to highlight a possible role of these and other micro-RNAs in the molecular pathways of schizophrenia.     

Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2'-O-methyltransferase nsp10/nsp16 complex

Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-adenosylmethionine-dependent (nucleoside-2'-O)-methyltransferase only active in the presence of its activating partner nsp10. We report the nsp10/nsp16 complex structure at 2.0 ? resolution, which shows nsp10 bound to nsp16 through a ～930 ?2 surface area in nsp10. Functional assays identify key residues involved in nsp10/nsp16 association, and in RNA binding or catalysis, the latter likely through a SN2-like mechanism. We present two other crystal structures, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in +RNA viruses.     

Designing cost‐effective biopharmaceutical facilities using mixed‐integer optimization

Chromatography operations are identified as critical steps in a monoclonal antibody (mAb) purification process and can represent a significant proportion of the purification material costs. This becomes even more critical with increasing product titers that result in higher mass loads onto chromatography columns, potentially causing capacity bottlenecks. In this work, a mixed‐integer nonlinear programming (MINLP) model was created and applied to an industrially relevant case study to optimize the design of a facility by determining the most cost‐effective chromatography equipment sizing strategies for the production of mAbs. Furthermore, the model was extended to evaluate the ability of a fixed facility to cope with higher product titers up to 15 g/L. Examination of the characteristics of the optimal chromatography sizing strategies across different titer values enabled the identification of the maximum titer that the facility could handle using a sequence of single column chromatography steps as well as multi‐column steps. The critical titer levels for different ratios of upstream to dowstream trains where multiple parallel columns per step resulted in the removal of facility bottlenecks were identified. Different facility configurations in terms of number of upstream trains were considered and the trade‐off between their cost and ability to handle higher titers was analyzed. The case study insights demonstrate that the proposed modeling approach, combining MINLP models with visualization tools, is a valuable decision‐support tool for the design of cost‐effective facility configurations and to aid facility fit decisions. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 29:1472–1483, 2013