Discussion of “Learning from Failure of a Long Curved Veneer Wall: Structural Analysis and Repair” by Paulo B. Lourenço and Pedro Medeiros

The authors, in an interesting and valuable paper, describe the failure of the brick-masonry veneer façade of a multiuse public hall in Gondomar, Portugal. Damage occurred within 2 years of construction. The veneer was a single leaf of continuous brick masonry tied to a RC structural wall, forming a cavity of nominal width 0.07 m that was partly filled with foamed polyurethane. The veneer wall was 242 m in length and 15 m in height, without movement joints, and extended around most of the elliptical perimeter of the building with portions facing north, east, and south. From their site investigations and technical analysis, the authors attributed the failure primarily to effects of “the irreversible expansion of clay brick,” apparent both from cracking and from extensive out-of-plane deformation of the wall, which had widened the cavity to as much as 0.13 m. Effects were greater on parts of the wall facing south. The failure analysis made use of a power law proposed by Wilson et al. (2003) to describe how expansive strain develops in fired-clay ceramics with time. Here, the discussers comment on recent fundamental work on moisture expansion in brick, and in particular on its temperature dependence, matters of direct relevance to the paper under discussion. The discussers’ comments support and extend the conclusions of the authors, with which the discussers broadly agree. Irreversible moisture expansion occurs as a result of slow chemical reactions between components of the fired-clay ceramic and environmental moisture (Hamilton and Hall 2012). The magnitude of the expansion varies strongly with brick mineralogy and kiln firing history, but a predictive model for expansion based on these factors does not yet exist. However, in general, highly crystalline engineering ceramics produced at high kiln temperatures expand less than low-fired ceramics with a higher amorphous content. The penalty is that high-fired ceramics tend to be more brittle and prone to cracking. It is now established that the expansive reaction continues indefinitely, although at a diminishing rate over all timescales; therefore, there is no well-defined time at which it ceases. Recent reanalysis of published data (Hall et al. 2011; Hall and Hoff 2012) shows that the equation e=at1/4 accurately describes expansion strain e over periods of time t as long as 65 years. It follows from this equation that expansive strain at 16 years is double the value at 1 year and three times the 1-year value at 81 years. The persistence of the expansion reaction, albeit at a diminishing rate, emphasizes the need to incorporate appropriate movement joints in masonry design. The authors mention the possibility of using a “poor mortar” to accommodate some of the expansive strain. The use of weak mortars undoubtedly explains the absence of expansion damage in some much-older buildings with thick brick walls. However, the discussers consider that in thin brick veneers, such as those used in Gondomar, a weak mortar is potentially dangerous. It is unfortunate both for design and for failure analysis that the test procedures generally used to characterize clay brick do not provide values of the expansivity a that are needed to apply the equation e=at1/4 . Accelerated steam tests, such as EN772-19 cited by the authors, are at best semiquantitative. In our view, it is essential to determine the expansivity from measurements of expansion strain made over an appropriate period of time under controlled conditions (Hall and Hoff 2012). The discussers also draw attention to the important practical matter of the temperature dependence of the moisture expansivity (Hall et al. 2013). The fact that moisture expansion is the direct consequence of a chemical rehydroxylation reaction (Hamilton and Hall 2012) ensures that the expansivity increases notably with temperature. Available data indicate that the activation energy (which controls the temperature dependence) is about 70 kJ/mol. This means, for example, that the expansivity a of any brick material is about 60% greater at a temperature of 30°C than it is at 10°C. Thus, if a limit expansion strain (say, 1×10−3) is reached in a particular material in 50 years at 10°C, the same strain is attained in the same material in only 7 years at 30°C. It seems likely that its strong temperature dependence explains why moisture expansion is perceived differently in different geographical regions [e.g., McNeilly (1985)] and generally receives more attention in regions with warmer climates, such as Australia, southern Asia, and Brazil. However, in any particular region, the magnitude of expansion and the associated damage within individual buildings are influenced by local temperature variations, in particular variations due to solar heat gain. In the Gondomar structure, deformation and cavity expansion were greatest in parts of the structure with a southern aspect, where the summer temperatures of the veneer are highest. The influence of aspect here is presumably exacerbated by the open situation of the building and by the insulation of the cavity where large temperature gradients might be expected. The discussers believe this large gradient acting over a thin veneer may partly explain such dramatic damage over a short period of time. A thicker brick cladding would probably fare better. Undoubtedly, there are also seasonal modulations of the expansion. The discussers have shown elsewhere how related thermal effects in the rehydroxylation of archaeological ceramics may be calculated (Hall et al. 2013)

Rising damp: capillary rise dynamics in walls

We analyse rising damp using the concepts and methods of unsaturated flow theory. A simple first-order Sharp Front model is developed which uses clear physical principles and includes the effects of evaporation and gravity. We find that the simple model captures well the observed features of capillary rise in walls and is supported by the underpinning nonlinear capillary diffusion theory. For most cases, capillary forces are dominant and the effects of gravity can be neglected

RuleMonkey: software for stochastic simulation of rule-based models

<p>Abstract</p> <p>Background</p> <p>The system-level dynamics of many molecular interactions, particularly protein-protein interactions, can be conveniently represented using reaction rules, which can be specified using model-specification languages, such as the BioNetGen language (BNGL). A set of rules implicitly defines a (bio)chemical reaction network. The reaction network implied by a set of rules is often very large, and as a result, generation of the network implied by rules tends to be computationally expensive. Moreover, the cost of many commonly used methods for simulating network dynamics is a function of network size. Together these factors have limited application of the rule-based modeling approach. Recently, several methods for simulating rule-based models have been developed that avoid the expensive step of network generation. The cost of these "network-free" simulation methods is independent of the number of reactions implied by rules. Software implementing such methods is now needed for the simulation and analysis of rule-based models of biochemical systems.</p> <p>Results</p> <p>Here, we present a software tool called RuleMonkey, which implements a network-free method for simulation of rule-based models that is similar to Gillespie's method. The method is suitable for rule-based models that can be encoded in BNGL, including models with rules that have global application conditions, such as rules for intramolecular association reactions. In addition, the method is rejection free, unlike other network-free methods that introduce null events, i.e., steps in the simulation procedure that do not change the state of the reaction system being simulated. We verify that RuleMonkey produces correct simulation results, and we compare its performance against DYNSTOC, another BNGL-compliant tool for network-free simulation of rule-based models. We also compare RuleMonkey against problem-specific codes implementing network-free simulation methods.</p> <p>Conclusions</p> <p>RuleMonkey enables the simulation of rule-based models for which the underlying reaction networks are large. It is typically faster than DYNSTOC for benchmark problems that we have examined. RuleMonkey is freely available as a stand-alone application <url>http://public.tgen.org/rulemonkey</url>. It is also available as a simulation engine within GetBonNie, a web-based environment for building, analyzing and sharing rule-based models.</p

Compositional landscape for glass formation in metal alloys

A high-resolution compositional map of glass-forming ability (GFA) in the Ni–Cr–Nb–P–B system is experimentally determined along various compositional planes. GFA is shown to be a piecewise continuous function formed by intersecting compositional subsurfaces, each associated with a nucleation pathway for a specific crystalline phase. Within each subsurface, GFA varies exponentially with composition, wheres exponential cusps in GFA are observed when crossing from one crystallization pathway to another. The overall GFA is shown to peak at multiple exponential hypercusps that are interconnected by ridges. At these compositions, quenching from the high-temperature melt yields glassy rods with diameters exceeding 1 cm, whereas for compositions far from these cusps the critical rod diameter drops precipitously and levels off to 1 to 2 mm. The compositional landscape of GFA is shown to arise primarily from an interplay between the thermodynamics and kinetics of crystal nucleation, or more precisely, from a competition between driving force for crystallization and liquid fragility

Practice Management Guidelines for the Diagnosis and Management of Injury in the Pregnant Patient: The EAST Practice Management Guidelines Work Group

Trauma during pregnancy has presented very unique challenges over the centuries. From the first report of Ambrose Pare of a gunshot wound to the uterus in the 1600s to the present, there have existed controversies and inconsistencies in diagnosis, management, prognostics, and outcome. Anxiety is heightened by the addition of another, smaller patient. Trauma affects 7% of all pregnancies and requires admission in 4 of 1000 pregnancies. The incidence increases with advancing gestational age. Just over half of trauma during pregnancy occurs in the third trimester. Motor vehicle crashes comprise 50% of these traumas, and falls and assaults account for 22% each. These data were considered to be underestimates because many injured pregnant patients are not seen at trauma centers. Trauma during pregnancy is the leading cause of nonobstetric death and has an overall 6% to 7% maternal mortality. Fetal mortality has been quoted as high as 61% in major trauma and 80% if maternal shock is present. The anatomy and physiology of pregnancy make diagnosis and treatment difficult

RPPA-based proteomics recognizes distinct epigenetic signatures in chronic lymphocytic leukemia with clinical consequences

The chronic lymphocytic leukemia (CLL) armamentarium has evolved significantly, with novel therapies that inhibit Bruton Tyrosine Kinase, PI3K delta and/or the BCL2 protein improving outcomes. Still, the clinical course of CLL patients is highly variable and most previously recognized prognostic features lack the capacity to predict response to modern treatments indicating the need for new prognostic markers. In this study, we identified four epigenetically distinct proteomic signatures of a large cohort of CLL and related diseases derived samples (n = 871) using reverse phase protein array technology. These signatures are associated with clinical features including age, cytogenetic abnormalities [trisomy 12, del(13q) and del(17p)], immunoglobulin heavy-chain locus (IGHV) mutational load, ZAP-70 status, Binet and Rai staging as well as with the outcome measures of time to treatment and overall survival. Protein signature membership was identified as predictive marker for overall survival regardless of other clinical features. Among the analyzed epigenetic proteins, EZH2, HDAC6, and loss of H3K27me3 levels were the most independently associated with poor survival. These findings demonstrate that proteomic based epigenetic biomarkers can be used to better classify CLL patients and provide therapeutic guidance

Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

Abstract Background Primary cardiac angiosarcomas are rare, but they are the most aggressive type of primary cardiac neoplasms. When patients do present, it is with advanced pulmonary and/or cardiac symptoms. Therefore, many times the correct diagnosis is not made at the time of initial presentation. These patients have metastatic disease and the vast majority of these patients die within a few months after diagnosis. Currently the treatment choices are limited and there are no targeted therapies available. Case presentation A 56-year-old male presented with shortness of breath, night sweats, and productive cough for a month. Workup revealed pericardial effusion and multiple bilateral pulmonary nodules suspicious for metastatic disease. Transthoracic echocardiogram showed a large pericardial effusion and a large mass in the base of the right atrium. Results of biopsy of bilateral lung nodules established a diagnosis of primary cardiac angiosarcoma. Aggressive pulmonary disease caused rapid deterioration; the patient went on hospice and subsequently died. Whole exome sequencing of the patient\u2019s postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4 , a negative regulator of TP53. Conclusion Mutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors

Methylglyoxal bis-guanylhydrazone in advanced bladder cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28924/1/0000761.pd

High Throughput Interrogation of Somatic Mutations in High Grade Serous Cancer of the Ovary

BACKGROUND:Epithelial ovarian cancer is the most lethal of all gynecologic malignancies, and high grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. The objective of this study was to determine the frequency and types of point somatic mutations in HGSC using a mutation detection protocol called OncoMap that employs mass spectrometric-based genotyping technology. METHODOLOGY/PRINCIPAL FINDINGS:The Center for Cancer Genome Discovery (CCGD) Program at the Dana-Farber Cancer Institute (DFCI) has adapted a high-throughput genotyping platform to determine the mutation status of a large panel of known cancer genes. The mutation detection protocol, termed OncoMap has been expanded to detect more than 1000 mutations in 112 oncogenes in formalin-fixed paraffin-embedded (FFPE) tissue samples. We performed OncoMap on a set of 203 FFPE advanced staged HGSC specimens. We isolated genomic DNA from these samples, and after a battery of quality assurance tests, ran each of these samples on the OncoMap v3 platform. 56% (113/203) tumor samples harbored candidate mutations. Sixty-five samples had single mutations (32%) while the remaining samples had ≥ 2 mutations (24%). 196 candidate mutation calls were made in 50 genes. The most common somatic oncogene mutations were found in EGFR, KRAS, PDGRFα, KIT, and PIK3CA. Other mutations found in additional genes were found at lower frequencies (<3%). CONCLUSIONS/SIGNIFICANCE:Sequenom analysis using OncoMap on DNA extracted from FFPE ovarian cancer samples is feasible and leads to the detection of potentially druggable mutations. Screening HGSC for somatic mutations in oncogenes may lead to additional therapies for this patient population