On the cohomology of pseudoeffective line bundles

The goal of this survey is to present various results concerning the cohomology of pseudoeffective line bundles on compact K{\"a}hler manifolds, and related properties of their multiplier ideal sheaves. In case the curvature is strictly positive, the prototype is the well known Nadel vanishing theorem, which is itself a generalized analytic version of the fundamental Kawamata-Viehweg vanishing theorem of algebraic geometry. We are interested here in the case where the curvature is merely semipositive in the sense of currents, and the base manifold is not necessarily projective. In this situation, one can still obtain interesting information on cohomology, e.g. a Hard Lefschetz theorem with pseudoeffective coefficients, in the form of a surjectivity statement for the Lefschetz map. More recently, Junyan Cao, in his PhD thesis defended in Grenoble, obtained a general K{\"a}hler vanishing theorem that depends on the concept of numerical dimension of a given pseudoeffective line bundle. The proof of these results depends in a crucial way on a general approximation result for closed (1,1)-currents, based on the use of Bergman kernels, and the related intersection theory of currents. Another important ingredient is the recent proof by Guan and Zhou of the strong openness conjecture. As an application, we discuss a structure theorem for compact K{\"a}hler threefolds without nontrivial subvarieties, following a joint work with F.Campana and M.Verbitsky. We hope that these notes will serve as a useful guide to the more detailed and more technical papers in the literature; in some cases, we provide here substantially simplified proofs and unifying viewpoints.Comment: 39 pages. This survey is a written account of a lecture given at the Abel Symposium, Trondheim, July 201

Performance evaluation and optimal design of supermarket refrigeration systems with supermarket model "SuperSim", Part II: Model applications

This is the post-print version of the final paper published in International Journal of Refrigeration. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2010 Elsevier B.V.As described in Part I, the supermarket simulation software “SuperSim” with its integrated refrigeration, building and HVAC system models, can be used to evaluate, compare and optimize alternative supermarket refrigeration systems. In Part II the model was used to evaluate and compare the performance of a CO2 booster refrigeration system with that of a conventional R404A multiplex system in a supermarket application. Floating head pressure control was implemented for both systems when they were in subcritical cycles. For the CO2 system, when the system was in transcritical cycle due to higher ambient air temperature, the head pressure was optimized through extensive thermodynamic cycle analysis as a function of ambient air temperature. The performance of the CO2 booster system in the supermarket was then simulated during a one year period and compared with that of the R404A system. As a result, the system performance will benefit from a lower ambient temperature and a sizeable heat recovery for the CO2 system

Subversion of actin dynamics by EspM effectors of attaching and effacing bacterial pathogens

Rho GTPases are common targets of bacterial toxins and type III secretion system effectors. IpgB1 and IpgB2 of Shigella and Map of enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli were recently grouped together on the basis that they share a conserved WxxxE motif. In this study, we characterized six WxxxE effectors from attaching and effacing pathogens: TrcA and EspM1 of EPEC strain B171, EspM1 and EspM2 of EHEC strain Sakai and EspM2 and EspM3 of Citrobacter rodentium. We show that EspM2 triggers formation of global parallel stress fibres, TrcA and EspM1 induce formation of localized parallel stress fibres and EspM3 triggers formation of localized radial stress fibres. Using EspM2 and EspM3 as model effectors, we report that while substituting the conserved Trp with Ala abolished activity, conservative Trp to Tyr or Glu to Asp substitutions did not affect stress-fibre formation. We show, using dominant negative constructs and chemical inhibitors, that the activity of EspM2 and EspM3 is RhoA and ROCK-dependent. Using Rhotekin pull-downs, we have shown that EspM2 and EspM3 activate RhoA; translocation of EspM2 and EspM3 triggered phosphorylation of cofilin. These results suggest that the EspM effectors modulate actin dynamics by activating the RhoA signalling pathway

Expression profiling of cyclin B1 and D1 in cervical carcinoma

Aim: Cyclins are a family of regulatory proteins that play a key role in controlling the cell cycle. Abnormalities of cell cycle regulators, including cyclins and cyclin dependent kinases, have been reported in various malignant tumors. This study was undertaken to quantitatively detect cyclin B1 and D1 in cervical cancer. Methods: A quantitative real-time reverse transcription polymerase chain reaction and Western blot assay were used to analyze the expression of cyclin B1/D1 mRNA and proteins, respectively, in fresh invasive cervical cancer (n = 41) and normal cervical tissues (n = 10). Results: There was significantly greater cyclin B1 expression in invasive cervical cancer than in normal cervical tissue (P = 0.019). However, cyclin D1 expression was not significantly different. A Western blot assay yielded similar results. Conclusion: Our results were consistent with the concept that up-regulation of cyclin B1 expression occurred in cervical cancer and an aberrant expression of cyclin B1 might play an important role in cervical carcinogenesis.Цель: циклины представляют собой семейство регуляторных белков, контролирующих клеточный цикл. Наличие функциональных и структурных нарушений регуляторов клеточного цикла (циклинов и циклинзависимых киназ) было отмечено в клетках различных злокачественных новообразований. Целью данного исследования было проведение количественного определения циклинов B1 и D1 в клетках рака шейки матки. Методы: определение уровня экспрессии циклинов B1/D1 (mRNA и белков соответственно) в свежеполученных клетках инвазивного рака шейки матки (n = 41) и нормальной ткани шейки матки (n = 10) проводили методами RT-PCR в режиме реального времени и Вестерн-блот анализа. Результаты: отмечен более высокий уровень экспрессии гена циклина В1 в клетках инвазивного рака шейки матки, чем в клетках нормальной ткани (P = 0,019). Не выявлены значительные различия в уровне экспрессии гена циклина D1. При Вестерн-блот анализе получены аналогичные результаты. Выводы: результаты исследования подтверждают концепцию об активации экспрессии циклина В1 при раке шейки матки. Аберрантная экспрессия циклина В1 может играть важную роль при злокачественной трансформации эпителия шейки матки

Restriction fragment mass polymorphism (RFMP) analysis based on MALDI-TOF mass spectrometry for detecting antiretroviral resistance in HIV-1 infected patients

AbstractViral genotype assessment is important for effective clinical management of HIV-1 infected patients, especially when access and/or adherence to antiretroviral treatment is reduced. In this study, we describe development of a matrix-assisted laser desorption/ionization-time of flight mass spectrometry-based viral genotyping assay, termed restriction fragment mass polymorphism (RFMP). This assay is suitable for sensitive, specific and high-throughput detection of multiple drug-resistant HIV-1 variants. One hundred serum samples from 60 HIV-1-infected patients previously exposed to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were analysed for the presence of drug-resistant viruses using the RFMP and direct sequencing assays. Probit analysis predicted a detection limit of 223.02 copies/mL for the RFMP assay and 1268.11 copies/mL for the direct sequencing assays using HIV-1 RNA Positive Quality Control Series. The concordance rates between the RFMP and direct sequencing assays for the examined codons were 97% (K65R), 97% (T69Ins/D), 97% (L74VI), 97% (K103N), 96% (V106AM), 97% (Q151M), 97% (Y181C), 97% (M184VI) and 94% (T215YF) in the reverse transcriptase coding region, and 100% (D30N), 100% (M46I), 100% (G48V), 100% (I50V), 100% (I54LS), 99% (V82A), 99% (I84V) and 100% (L90M) in the protease coding region. Defined mixtures were consistently and accurately identified by RFMP at 5% relative concentration of mutant to wild-type virus while at 20% or greater by direct sequencing. The RFMP assay based on mass spectrometry proved to be sensitive, accurate and reliable for monitoring the emergence and early detection of HIV-1 genotypic variants that lead to drug resistance

Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

ArticleBackground: Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus. Methods: A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs. Results: Using different statistical methods,MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing formisclassification among long-terminfections indicated that overall PFRs were 0.6%to 2.5%at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C). Conclusions: Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.This research has been supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC)

Treatment Guidance for Patients With Lung Cancer During the Coronavirus 2019 Pandemic.

The global coronavirus disease 2019 pandemic continues to escalate at a rapid pace inundating medical facilities and creating substantial challenges globally. The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer seems to be higher, especially as they are more likely to present with an immunocompromised condition, either from cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection currently remain poorly characterized and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause considerable disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary comorbidities are more likely to have increased risk and mortality from coronavirus disease 2019 as one of its common manifestations is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available

Does accelerating universe indicates Brans-Dicke theory

The evolution of universe in Brans-Dicke (BD) theory is discussed in this paper. Considering a parameterized scenario for BD scalar field $\phi=\phi_{0}a^{\alpha}$ which plays the role of gravitational "constant" $G$, we apply the Markov Chain Monte Carlo method to investigate a global constraints on BD theory with a self-interacting potential according to the current observational data: Union2 dataset of type supernovae Ia (SNIa), high-redshift Gamma-Ray Bursts (GRBs) data, observational Hubble data (OHD), the cluster X-ray gas mass fraction, the baryon acoustic oscillation (BAO), and the cosmic microwave background (CMB) data. It is shown that an expanded universe from deceleration to acceleration is given in this theory, and the constraint results of dimensionless matter density $\Omega_{0m}$ and parameter $\alpha$ are, $\Omega_{0m}=0.286^{+0.037+0.050}_{-0.039-0.047}$ and $\alpha=0.0046^{+0.0149+0.0171}_{-0.0171-0.0206}$ which is consistent with the result of current experiment exploration, $\mid\alpha\mid \leq 0.132124$. In addition, we use the geometrical diagnostic method, jerk parameter $j$, to distinguish the BD theory and cosmological constant model in Einstein's theory of general relativity.Comment: 16 pages, 3 figure

A coupled 3D isogeometric and discrete element approach for modelling interactions between structures and granular matters

A three-dimensional (3D) isogeometric/discrete-element coupling method is presented for modelling contact/impact between structures and particles. This method takes advantages of the geometry smoothness and exactness of isogeometric analysis (IGA) for continuous solid media and the effectiveness and flexibility of the discrete element method (DEM) for particulate matters. The coupling procedure for handling interactions between IGA elements and discrete elements (DEs) includes global search, local search and interaction calculation. In the global search, the CGRID method is modified to detect potential contact pairs between IGA elements and DEs based on their bounding box representations. The strong convex hull property of a NURBS control mesh plays an important part in the bounding box representation of IGA elements. In the local search, the proposed approach treats each spherical DE centroid as a slave node and the contact surface of each IGA element as the master surface. The projection of a DE centroid onto an IGA element contact surface is solved by modifying the simplex method and Brent iterations. The contact force between an IGA element and a DE is determined from their penetration by using a (nonlinear) penalty function based method. The whole coupled system is solved by the explicit time integration within a updated Lagrangian scheme. Finally, three impact examples, including the impact of two symmetric bars, a tube onto a footing strip, and an assembly of granular particles to a tailor rolled blank, are simulated in elastic regime to assess the accuracy and applicability of the proposed method

Characterization of Loading Responses and Failure Loci of a Boron Steel Spot Weld

Boron steel, classed as an ultra high-strength steel (UHSS), has been utilized in anti-intrusion systems in automobiles, providing high strength and weight-saving potential through gage reduction. UHSS spot welds exhibit unique hardness distributions, with a hard nugget and outlying base material, but with a soft heat-affected zone in-between these regions. This soft zone reduces the strength of the weld and makes it susceptible to failure. Due to the interaction of various weld zones that occurs during loading, there is a need to characterize the loading response of the weld for accurate failure predictions. The loading response of certain weld zones, as well as failure loci, was obtained through physical simulation of the welding process. The results showed a significant difference in mechanical behavior through the weld length. An important result is that instrumented indentation was shown to be a valid, quantitative method for verifying the accuracy with which weld microstructure has been recreated with regard to the target weld microstructure