Hierarchical Graph Transformation

If systems are specified by graph transformation, large graphs should be structured in order to be comprehensible. In this paper, we present an approach for the rule-based transformation of hierarchically structured (hyper)graphs. In these graphs, distinguished hyperedges contain graphs that can be hierarchical again. Our framework extends the well-known double-pushout approach from at to hierarchical graphs. In particular, we show how pushouts and pushout complements of hierarchical graphs and graph morphisms can be constructed recursively. Moreover, we make rules more expressive by introducing variables which allow to copy and to remove hierarchical subgraphs in a single rule application

Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making. Copyright (C) 2011 S. Karger AG, Base

MaDe4IC: an abstract method for managing model dependencies in inter-organizational cooperations

Inter-organizational cooperations are complex in terms of coordination, agreements, and value creation for involved partners. When managing complex cooperations, it is vital to maintain models describing them. Changing one model to regain consistency with the running system might result in new inconsistencies. As a consequence, this maintenance phase grows in complexity with increasing number of models. In this context, challenges are to ensure consistency at design time and to monitor the system at runtime, i.e., at design time, consistency between different models describing the cooperation needs to be ensured. At runtime, behavior of the software system needs to be compared with its underlying models. In this paper, we propose a structured and model-independent method that supports ensuring and maintaining consistency between running system and underlying models for inter-organizational cooperations

The histone demethylase LSD1/KDM1A promotes the DNA damage response

Histone demethylation is known to regulate transcription, but its role in other processes is largely unknown. We report a role for the histone demethylase LSD1/KDM1A in the DNA damage response (DDR). We show that LSD1 is recruited directly to sites of DNA damage. H3K4 dimethylation, a major substrate for LSD1, is reduced at sites of DNA damage in an LSD1-dependent manner. The E3 ubiquitin ligase RNF168 physically interacts with LSD1 and we find this interaction to be important for LSD1 recruitment to DNA damage sites. Although loss of LSD1 did not affect the initial formation of pH2A.X foci, 53BP1 and BRCA1 complex recruitment were reduced upon LSD1 knockdown. Mechanistically, this was likely a result of compromised histone ubiquitylation preferentially in late S/G2. Consistent with a role in the DDR, knockdown of LSD1 resulted in moderate hypersensitivity to γ-irradiation and increased homologous recombination. Our findings uncover a direct role for LSD1 in the DDR and place LSD1 downstream of RNF168 in the DDR pathway

Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends

In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved ∼125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an α-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer. Engagement of the Rif1-NTD with telomeres proved essential for checkpoint control and telomere length regulation. Unexpectedly, Rif1-NTD also promoted NHEJ at DNA breaks in yeast, revealing a conserved role of Rif1 in DNA repair. We propose that tight associations between the Rif1-NTD and DNA gate access of processing factors to DNA ends, enabling Rif1 to mediate diverse telomere maintenance and DNA repair functions

Temperature Dependence Study of the Kinetics and Product Yields of the HO_2 + CH_3C(O)O_2 Reaction by Direct Detection of OH and HO_2 Radicals Using 2f-IR Wavelength Modulation Spectroscopy

The HO_2 + CH_3C(O)O_2 reaction consists of three product channels: CH_3C(O)OOH + O_2 (R1a), CH_3C(O)OH + O_3 (R1b), and OH + CH_3C(O)O + O_2 (R1c). The overall rate constant (k_1) and product yields (α_(1a), α_(1b), and α_(1c)) were determined over the atmospherically-relevant temperature range of 230 - 294 K at 100 Torr in N_2. Time resolved kinetics measurements were performed in a pulsed laser photolysis experiment in a slow flow cell employing simultaneous infrared (IR) and ultraviolet (UV) absorption spectroscopy. HO_2 and CH_3C(O)O_2 were formed by Cl-atom reactions with CH_3OH and CH_3CHO, respectively. Heterodyne near- and mid-infrared (NIR and MIR) wavelength modulation spectroscopy (WMS) was employed to selectively detect HO_2 and OH radicals. Ultraviolet absorption at 225 nm and 250 nm was used to detect various peroxy radicals as well as ozone (O_3). These experimental techniques enabled direct measurements of α_(1c) and α_(1b) via time-resolved spectroscopic detection in the MIR and the UV, respectively. At each temperature, experiments were performed at various ratios of initial HO_2 and CH_3C(O)O_2 concentrations to quantify the secondary chemistry. The Arrhenius expression was found to be k1(T) = 1.38^(+1.17)_(-0.63)×10^(-12)exp[(730±170)/T] cm^(-3) molecule^(-1) s^(-1). Α_(1a) was temperature-independent while α_(1b) and α_(1c) increased and decreased, respectively, with increasing temperatures. These trends are consistent with the current recommendation by the IUPAC data evaluation. Hydrogen-bonded adducts of HO_2 with the precursors, HO_2.CH_3OH and HO_2.CH_3CHO, played a role at lower temperatures; as part of this work, kinetics of the adducts were also measured

Temperature Dependence Study of the Kinetics and Product Yields of the HO_2 + CH_3C(O)O_2 Reaction by Direct Detection of OH and HO_2 Radicals Using 2f-IR Wavelength Modulation Spectroscopy

The HO_2 + CH_3C(O)O_2 reaction consists of three product channels: CH_3C(O)OOH + O_2 (R1a), CH_3C(O)OH + O_3 (R1b), and OH + CH_3C(O)O + O_2 (R1c). The overall rate constant (k_1) and product yields (α_(1a), α_(1b), and α_(1c)) were determined over the atmospherically-relevant temperature range of 230 - 294 K at 100 Torr in N_2. Time resolved kinetics measurements were performed in a pulsed laser photolysis experiment in a slow flow cell employing simultaneous infrared (IR) and ultraviolet (UV) absorption spectroscopy. HO_2 and CH_3C(O)O_2 were formed by Cl-atom reactions with CH_3OH and CH_3CHO, respectively. Heterodyne near- and mid-infrared (NIR and MIR) wavelength modulation spectroscopy (WMS) was employed to selectively detect HO_2 and OH radicals. Ultraviolet absorption at 225 nm and 250 nm was used to detect various peroxy radicals as well as ozone (O_3). These experimental techniques enabled direct measurements of α_(1c) and α_(1b) via time-resolved spectroscopic detection in the MIR and the UV, respectively. At each temperature, experiments were performed at various ratios of initial HO_2 and CH_3C(O)O_2 concentrations to quantify the secondary chemistry. The Arrhenius expression was found to be k1(T) = 1.38^(+1.17)_(-0.63)×10^(-12)exp[(730±170)/T] cm^(-3) molecule^(-1) s^(-1). Α_(1a) was temperature-independent while α_(1b) and α_(1c) increased and decreased, respectively, with increasing temperatures. These trends are consistent with the current recommendation by the IUPAC data evaluation. Hydrogen-bonded adducts of HO_2 with the precursors, HO_2.CH_3OH and HO_2.CH_3CHO, played a role at lower temperatures; as part of this work, kinetics of the adducts were also measured

School Absenteeism As an Adjunct Surveillance Indicator: Experience during the Second Wave of the 2009 H1N1 Pandemic in Quebec, Canada

A school absenteeism surveillance system was implemented in the province of Quebec, Canada during the second wave of the 2009 H1N1 pandemic. This paper compares this surveillance approach with other available indicators.All (3432) elementary and high schools from Quebec were included. Each school was required to report through a web-based system any day where the proportion of students absent for influenza-like illness (ILI) exceeded 10% of current school enrolment.Between October 18 and December 12 2009, 35.6% of all schools met the 10% absenteeism threshold. This proportion was greater in elementary compared to high schools (40% vs 19%) and in smaller compared to larger schools (44% vs 22%). The maximum absenteeism rate was reached the first day of reporting or within the next two days in 55% and 31% of schools respectively. The first reports and subsequent peak in school absenteeism provincially preceded the peak in paediatric hospitalization by two and one weeks, respectively. Trends in school surveillance otherwise mirrored other indicators.During a pandemic, school outbreak surveillance based on a 10% threshold appears insufficient to trigger timely intervention within a given affected school. However, school surveillance appears well-correlated and slightly anticipatory compared to other population indicators. As such, school absenteeism warrants further evaluation as an adjunct surveillance indicator whose overall utility will depend upon specified objectives, and other existing capacity for monitoring and response

FIGNL1 inhibits homologous recombination in BRCA2 deficient cells by dissociating RAD51 filaments

Homologous recombination (HR) deficiency upon BRCA2 loss arises from defects in the formation of RAD51 nucleoprotein filaments. Here, we demonstrate that loss of the anti-recombinase FIGNL1 retains RAD51 loading at DNA double-stranded breaks (DSBs) in BRCA2-deficient cells, leading to genome stability, HR proficiency, and viability of BRCA2-deficient mouse embryonic stem cells. Mechanistically, we directly show that strand invasion and subsequent HR defects upon BRCA2 loss primarily arises from the unrestricted removal of RAD51 from DSB sites by FIGNL1, rather than from defective RAD51 loading. Furthermore, we identify that the MMS22L-TONSL complex interacts with FIGNL1 and is critical for HR in BRCA2/FIGNL1 double-deficient cells. These findings identify a pathway for tightly regulating RAD51 activity to promote efficient HR, offering insights into mechanisms of chemoresistance in BRCA2-deficient tumors

Confluence up to Garbage

No abstract available