Black holes in supergravity and integrability

Stationary black holes of massless supergravity theories are described by certain geodesic curves on the target space that is obtained after dimensional reduction over time. When the target space is a symmetric coset space we make use of the group-theoretical structure to prove that the second order geodesic equations are integrable in the sense of Liouville, by explicitly constructing the correct amount of Hamiltonians in involution. This implies that the Hamilton-Jacobi formalism can be applied, which proves that all such black hole solutions, including non-extremal solutions, possess a description in terms of a (fake) superpotential. Furthermore, we improve the existing integration method by the construction of a Lax integration algorithm that integrates the second order equations in one step instead of the usual two step procedure. We illustrate this technology with a specific example.Comment: 44 pages, small typos correcte

A specification-based QoS-aware design framework for service-based applications

Effective and accurate service discovery and composition rely on complete specifications of service behaviour, containing inputs and preconditions that are required before service execution, outputs, effects and ramifications of a successful execution and explanations for unsuccessful executions. The previously defined Web Service Specification Language (WSSL) relies on the fluent calculus formalism to produce such rich specifications for atomic and composite services. In this work, we propose further extensions that focus on the specification of QoS profiles, as well as partially observable service states. Additionally, a design framework for service-based applications is implemented based on WSSL, advancing state of the art by being the first service framework to simultaneously provide several desirable capabilities, such as supporting ramifications and partial observability, as well as non-determinism in composition schemas using heuristic encodings; providing explanations for unexpected behaviour; and QoS-awareness through goal-based techniques. These capabilities are illustrated through a comparative evaluation against prominent state-of-the-art approaches based on a typical SBA design scenario

Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy

We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging. Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin

Endocrine therapy and related issues in hormone receptor-positive early breast cancer: a roundtable discussion by the breast cancer therapy expert group (BCTEG)

Purpose: Management of breast cancer is a rapidly evolving field, and, although evidence-based guidelines are available for clinicians to provide direction on critical issues in patient care, clinicians often left to address these issues in the context of community practice situations with their patients. These include the patient’s comorbid conditions, actual versus perceived benefit of treatments, patient’s compliance as well as financial/reimbursement issues, and long-term tolerability of therapy. Methods: A meeting of global oncology experts was convened in January 2017 with the belief that there is a gap in clinical practice guidance on several fundamental issues in breast cancer care, particularly in the community setting, where oncologists may encounter multiple tumor types. The goal was to discuss some of the most important questions in this area and provide some guidance for practicing oncologists. Results: Topics addressed included risk of contralateral breast cancer recurrence in patients with estrogen receptor-positive early breast cancer who have undergone 5 years of adjuvant endocrine therapy, adverse events associated with endocrine therapy and their management, emergent data on adjuvant bisphosphonate therapy and its apparent benefit in reducing breast cancer recurrence, recent findings of extended adjuvant endocrine therapy trials, and the use of currently available genomic biomarker tests as a means of further informing treatment decisions. Conclusions: A summary of the discussion on these topics and several ‘expert opinion statements’ are provided herein in an effort to convey the collective insights of the panel as it relates to current standard practice

Combinatorial experimental protocols for Erbicin-derived immunoagents and Herceptin

Erbicin is a human anti-ErbB2 single-chain antibody fragment with high affinity and selectivity for ErbB2-positive cancer cells. Two anti-ErbB2 immunoconjugates, called Erb-hRNase and Erb-hcAb, have been prepared and found to be selectively cytotoxic on ErbB2-positive cancer cells in vitro and vivo. In Erb-hRNase, Erbicin is linked to a human RNase and in Erb-hcAb it is linked to the key structural and functional regions of a human IgG. Herceptin is an anti-ErbB2 humanised antibody successfully used in the immunotherapy of breast cancer. We report here that the Erbicin-derived immunoagents target on breast cancer cells an ErbB2 epitope different than that of Herceptin. This finding led us to verify the effects of Herceptin on breast cancer cells when it was used in combination with the Erbicin-derived immunoagents. The results indicated that in combination experiments the antitumour action of Herceptin and that of the novel agents were significantly increased in an additive fashion. An inspection of the mechanism of action of Erb-hRNase or Erb-hcAb combined with Herceptin provided evidence that the antibody combinations engendered an increased downregulation of the ErbB2 receptor, and led to an enhanced apoptotic cell death

Laser capture microdissection (LCM) and whole genome amplification (WGA) of DNA from normal breast tissue --- optimization for genome wide array analyses

<p>Abstract</p> <p>Background</p> <p>Laser capture microdissection (LCM) can be applied to tissues where cells of interest are distinguishable from surrounding cell populations. Here, we have optimized LCM for fresh frozen normal breast tissue where large amounts of fat can cause problems during microdissection. Since the amount of DNA needed for genome wide analyses, such as single nucleotide polymorphism (SNP) arrays, is often greater than what can be obtained from the dissected tissue, we have compared three different whole genome amplification (WGA) kits for amplification of DNA from LCM material. In addition, the genome wide profiling methods commonly used today require extremely high DNA quality compared to PCR based techniques and DNA quality is thus critical for successful downstream analyses.</p> <p>Findings</p> <p>We found that by using FrameSlides without glass backing for LCM and treating the slides with acetone after staining, the problems caused by excessive fat could be significantly decreased. The amount of DNA obtained after extraction from LCM tissue was not sufficient for direct SNP array analysis in our material. However, the two WGA kits based on Phi29 polymerase technology (Repli-g^®(Qiagen) and GenomiPhi (GE Healthcare)) gave relatively long amplification products, and amplified DNA from Repli-g^®gave call rates in the subsequent SNP analysis close to those from non-amplified DNA. Furthermore, the quality of the input DNA for WGA was found to be essential for successful SNP array results and initial DNA fragmentation problems could be reduced by switching from a regular halogen lamp to a VIS-LED lamp during LCM.</p> <p>Conclusions</p> <p>LCM must be optimized to work satisfactorily in difficult tissues. We describe a work flow for fresh frozen normal breast tissue where fat is inclined to cause problems if sample treatment is not adapted to this tissue. We also show that the Phi29-based Repli-g^®WGA kit (Qiagen) is a feasible approach to amplify DNA of high quality prior to genome wide analyses such as SNP profiling.</p

Nasal Carriage and Antimicrobial Susceptibility of Staphylococcus aureus in healthy preschool children in Ujjain, India

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that community acquired <it>S. aureus </it>infections are spreading among healthy children. Nasal colonization with <it>S. aureus </it>plays pivotal role in the increasing prevalence of resistant community acquired <it>S. aureus </it>infections worldwide. A regular surveillance system is important in ensuring quality of patient care. The aim of the study was to assess the prevalence of and the factors associated with nasal carriage of <it>S. aureus </it>and its antibiotic sensitivity pattern among healthy children in Ujjain, India.</p> <p>Methods</p> <p>A prospective study was done in paediatric outpatient clinics of R.D. Gardi medical college Ujjain, India. Healthy children from 1 month to 59 months of age were included. Information on previously known risk factors for nasal colonization was collected using a pre-tested questionnaire. Swabs from anterior nares were collected and transported in Amies transport media with charcoal and cultured on 5% sheep blood agar. Antibiotic sensitivity tests were performed using Kirby Bauer's disc diffusion method according to performance standards of Clinical and Laboratory Standard Institute guidelines.</p> <p>Results</p> <p>Of the 1,562 children from 1-month up-to five years of age included in the study 98 children tested positive for nasal carriage of <it>S. aureus</it>. The prevalence of nasal carriage of <it>S. aureus </it>was 6.3% (95% CI 5.1-7.5) out of which 16.3% (95% CI 8.9-23.8) were methicillin-resistant <it>S. aureus </it>(MRSA). The factors associated with nasal carriage were "child attending preschool" (OR 4.26, 95% CI 2.25-8.03; <it>P </it>= 0.007) or "school" (OR 3.02, 95% CI 1.27-7.18; <it>P </it>< 0.001) and "family size more than 10 members" (OR 2.76 95% CI 1.06-7.15; <it>P </it>= 0.03). The sensitivity pattern of isolated <it>S. aureus </it>showed resistance to commonly used oral antibiotics while resistance to glycopeptides was not noted.</p> <p>Conclusions</p> <p>We found a relatively low rate of nasal carriage of <it>S. aureus </it>in children below five years when compared to children of older age groups in India. Yet, prevalence of MRSA was relatively high.</p

Recent trend reversal for declining European seagrass meadows

Seagrass meadows, key ecosystems supporting fisheries, carbon sequestration and coastal protection, are globally threatened. In Europe, loss and recovery of seagrasses are reported, but the changes in extent and density at the continental scale remain unclear. Here we collate assessments of changes from 1869 to 2016 and show that 1/3 of European seagrass area was lost due to disease, deteriorated water quality, and coastal development, with losses peaking in the 1970s and 1980s. Since then, loss rates slowed down for most of the species and fastgrowing species recovered in some locations, making the net rate of change in seagrass area experience a reversal in the 2000s, while density metrics improved or remained stable in most sites. Our results demonstrate that decline is not the generalised state among seagrasses nowadays in Europe, in contrast with global assessments, and that deceleration and reversal of declining trends is possible, expectingly bringing back the services they provide