Alkali metal distribution in composite cement pastes and its relation to accelerated ASR tests

Accelerated testing of alkali silica reaction (ASR) in concrete at elevated temperatures of 38 and 60 °C has an unknown impact on the alkali metal distribution in the cement paste. This paper investigates how the alkali metals released from hydrating Portland cement, limestone, and SCMs distribute between non-reactive and unreacted phases, C-A-S-H, and the pore solution. The SCMs investigated were fly ash and a volcanic pozzolan. The hydrate assemblage and pore solution of cement pastes cured at 20, 38 and 60 °C were analysed and related to the expansion of concrete prisms. There is little difference in alkali metal distribution at 20 and 38 °C, whereas curing at 60 °C has a large impact for the SCM containing blends. At alkali metal concentrations in the pore solution below 0.5 mol/L (Na + K) expansion of concrete was suppressed. Pore solution analysis could be used to screen new SCMs for ASR mitigation.publishedVersio

A functional spleen contributes to afucosylated IgG in humans

As a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells

FMAP: Distributed Cooperative Multi-Agent Planning

This paper proposes FMAP (Forward Multi-Agent Planning), a fully-distributed multi-agent planning method that integrates planning and coordination. Although FMAP is specifically aimed at solving problems that require cooperation among agents, the flexibility of the domain-independent planning model allows FMAP to tackle multi-agent planning tasks of any type. In FMAP, agents jointly explore the plan space by building up refinement plans through a complete and flexible forward-chaining partial-order planner. The search is guided by h D T G , a novel heuristic function that is based on the concepts of Domain Transition Graph and frontier state and is optimized to evaluate plans in distributed environments. Agents in FMAP apply an advanced privacy model that allows them to adequately keep private information while communicating only the data of the refinement plans that is relevant to each of the participating agents. Experimental results show that FMAP is a general-purpose approach that efficiently solves tightly-coupled domains that have specialized agents and cooperative goals as well as loosely-coupled problems. Specifically, the empirical evaluation shows that FMAP outperforms current MAP systems at solving complex planning tasks that are adapted from the International Planning Competition benchmarks.This work has been partly supported by the Spanish MICINN under projects Consolider Ingenio 2010 CSD2007-00022 and TIN2011-27652-C03-01, the Valencian Prometeo project II/2013/019, and the FPI-UPV scholarship granted to the first author by the Universitat Politecnica de Valencia.Torreño Lerma, A.; Onaindia De La Rivaherrera, E.; Sapena Vercher, O. (2014). FMAP: Distributed Cooperative Multi-Agent Planning. Applied Intelligence. 41(2):606-626. https://doi.org/10.1007/s10489-014-0540-2S606626412Benton J, Coles A, Coles A (2012) Temporal planning with preferences and time-dependent continuous costs. In: Proceedings of the 22nd international conference on automated planning and scheduling (ICAPS). AAAI, pp 2–10Borrajo D. (2013) Multi-agent planning by plan reuse. In: Proceedings of the 12th international conference on autonomous agents and multi-agent systems (AAMAS). IFAAMAS, pp 1141–1142Boutilier C, Brafman R (2001) Partial-order planning with concurrent interacting actions. J Artif Intell Res 14(105):136Brafman R, Domshlak C (2008) From one to many: planning for loosely coupled multi-agent systems. In: Proceedings of the 18th international conference on automated planning and scheduling (ICAPS). AAAI, pp 28–35Brenner M, Nebel B (2009) Continual planning and acting in dynamic multiagent environments. J Auton Agents Multiagent Syst 19(3):297–331Bresina J, Dearden R, Meuleau N, Ramakrishnan S, Smith D, Washington R (2002) Planning under continuous time and resource uncertainty: a challenge for AI. 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Appl Intell:1–22Koehler J, Ottiger D (2002) An AI-based approach to destination control in elevators. AI Mag 23(3):59–78Kovacs DL (2011) Complete BNF description of PDDL3.1. Technical reportvan der Krogt R (2009) Quantifying privacy in multiagent planning. Multiagent Grid Syst 5(4):451–469Kvarnström J (2011) Planning for loosely coupled agents using partial order forward-chaining. In: Proceedings of the 21st international conference on automated planning and scheduling (ICAPS). AAAI, pp 138–145Lesser V, Decker K, Wagner T, Carver N, Garvey A, Horling B, Neiman D, Podorozhny R, Prasad M, Raja A et al (2004) Evolution of the GPGP/TAEMS domain-independent coordination framework. Auton Agents Multi-Agent Syst 9(1–2):87–143Long D, Fox M (2003) The 3rd international planning competition: results and analysis. J Artif Intell Res 20:1–59Nissim R, Brafman R, Domshlak C (2010) A general, fully distributed multi-agent planning algorithm. 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A functional spleen contributes to afucosylated IgG in humans

As a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography-mass spectrometry (LC-MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.Proteomic

Phylogenetic Relationships of the Marine Haplosclerida (Phylum Porifera) Employing Ribosomal (28S rRNA) and Mitochondrial (cox1, nad1) Gene Sequence Data

The systematics of the poriferan Order Haplosclerida (Class Demospongiae) has been under scrutiny for a number of years without resolution. Molecular data suggests that the order needs revision at all taxonomic levels. Here, we provide a comprehensive view of the phylogenetic relationships of the marine Haplosclerida using many species from across the order, and three gene regions. Gene trees generated using 28S rRNA, nad1 and cox1 gene data, under maximum likelihood and Bayesian approaches, are highly congruent and suggest the presence of four clades. Clade A is comprised primarily of species of Haliclona and Callyspongia, and clade B is comprised of H. simulans and H. vansoesti (Family Chalinidae), Amphimedon queenslandica (Family Niphatidae) and Tabulocalyx (Family Phloeodictyidae), Clade C is comprised primarily of members of the Families Petrosiidae and Niphatidae, while Clade D is comprised of Aka species. The polyphletic nature of the suborders, families and genera described in other studies is also found here

Bortezomib maintenance after R-CHOP, cytarabine and autologous stem cell transplantation in newly diagnosed patients with mantle cell lymphoma, results of a randomised phase II HOVON trial

Rituximab-containing induction followed by autologous stem cell transplantation (ASCT) is the standard first-line treatment for young mantle cell lymphoma patients. However, most patients relapse after ASCT. We investigated in a randomised phase II study the outcome of a chemo-immuno regimen and ASCT with or without maintenance therapy with bortezomib. Induction consisted of three cycles R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles high-dose cytarabine, BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT. Patients responding were randomised between bortezomib maintenance (1·3 mg/m2 intravenously once every 2 weeks, for 2 years) and observation. Of 135 eligible patients, 115 (85%) proceeded to ASCT, 60 (44%) were randomised. With a median follow-up of 77·5 months for patients still alive, 5-year event-free survival (EFS) was 51% (95% CI 42–59%); 5-year overall survival (OS) was 73% (95% CI 65–80%). The median follow-up of randomised patients still alive was 71·5 months. Patients with bortezomib maintenance had a 5-year EFS of 63% (95% CI 44–78%) and 5-year OS of 90% (95% CI 72–97%). The patients randomised to observation had 5-year PFS of 60% (95% CI, 40–75%) and OS of 90% (95% CI 72–97%). In conclusion, in this phase II study we found no indication of a positive effect of bortezomib maintenance after ASCT

Phase II study of carfilzomib, thalidomide, and low-dose dexamethasone as induction and consolidation in newly diagnosed, transplant eligible patients with multiple myeloma; the Carthadex trial

This is a phase II dose escalation trial of carfilzomib in combination with thalidomide and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The results of four dose levels are reported. Induction therapy consisted of four cycles of carfilzomib 20/27 mg/m2 (n=50), 20/36 mg/m2 (n=20), 20/45 mg/m2 (n=21), and 20/56 mg/m2 (n=20) on days 1, 2, 8, 9, 15, 16 of a 28-day cycle; thalidomide 200 mg on day 1 through 28 and dexamethasone 40 mg weekly. Induction therapy was followed by high-dose melphalan and autologous stem cell transplantation and consolidation therapy with four cycles of carfilzomib, thalidomide and dexamethasone in the same schedule except a lower dose of thalidomide (50 mg). Very good partial response rate or better and complete response rate or better after ind

Process Mining for Six Sigma

Process mining offers a set of techniques for gaining data-based insights into business processes from event logs. The literature acknowledges the potential benefits of using process mining techniques in Six Sigma-based process improvement initiatives. However, a guideline that is explicitly dedicated on how process mining can be systematically used in Six Sigma initiatives is lacking. To address this gap, the Process Mining for Six Sigma (PMSS) guideline has been developed to support organizations in systematically using process mining techniques aligned with the DMAIC (Define-Measure-Analyze-Improve-Control) model of Six Sigma. Following a design science research methodology, PMSS and its tool support have been developed iteratively in close collaboration with experts in Six Sigma and process mining, and evaluated by means of focus groups, demonstrations and interviews with industry experts. The results of the evaluations indicate that PMSS is useful as a guideline to support Six Sigma-based process improvement activities. It offers a structured guideline for practitioners by extending the DMAIC-based standard operating procedure. PMSS can help increasing the efficiency and effectiveness of Six Sigma-based process improving efforts. This work extends the body of knowledge in the fields of process mining and Six Sigma, and helps closing the gap between them. Hence, it contributes to the broad field of quality management

The steel–concrete interface

Although the steel–concrete interface (SCI) is widely recognized to influence the durability of reinforced concrete, a systematic overview and detailed documentation of the various aspects of the SCI are lacking. In this paper, we compiled a comprehensive list of possible local characteristics at the SCI and reviewed available information regarding their properties as well as their occurrence in engineering structures and in the laboratory. Given the complexity of the SCI, we suggested a systematic approach to describe it in terms of local characteristics and their physical and chemical properties. It was found that the SCI exhibits significant spatial inhomogeneity along and around as well as perpendicular to the reinforcing steel. The SCI can differ strongly between different engineering structures and also between different members within a structure; particular differences are expected between structures built before and after the 1970/1980s. A single SCI representing all on-site conditions does not exist. Additionally, SCIs in common laboratory-made specimens exhibit significant differences compared to engineering structures. Thus, results from laboratory studies and from practical experience should be applied to engineering structures with caution. Finally, recommendations for further research are made

Elevated Levels of the Polo Kinase Cdc5 Override the Mec1/ATR Checkpoint in Budding Yeast by Acting at Different Steps of the Signaling Pathway

Checkpoints are surveillance mechanisms that constitute a barrier to oncogenesis by preserving genome integrity. Loss of checkpoint function is an early event in tumorigenesis. Polo kinases (Plks) are fundamental regulators of cell cycle progression in all eukaryotes and are frequently overexpressed in tumors. Through their polo box domain, Plks target multiple substrates previously phosphorylated by CDKs and MAPKs. In response to DNA damage, Plks are temporally inhibited in order to maintain the checkpoint-dependent cell cycle block while their activity is required to silence the checkpoint response and resume cell cycle progression. Here, we report that, in budding yeast, overproduction of the Cdc5 polo kinase overrides the checkpoint signaling induced by double strand DNA breaks (DSBs), preventing the phosphorylation of several Mec1/ATR targets, including Ddc2/ATRIP, the checkpoint mediator Rad9, and the transducer kinase Rad53/CHK2. We also show that high levels of Cdc5 slow down DSB processing in a Rad9-dependent manner, but do not prevent the binding of checkpoint factors to a single DSB. Finally, we provide evidence that Sae2, the functional ortholog of human CtIP, which regulates DSB processing and inhibits checkpoint signaling, is regulated by Cdc5. We propose that Cdc5 interferes with the checkpoint response to DSBs acting at multiple levels in the signal transduction pathway and at an early step required to resect DSB ends