Non-ergodicity of the motion in three dimensional steep repelling dispersing potentials

It is demonstrated numerically that smooth three degrees of freedom Hamiltonian systems which are arbitrarily close to three dimensional strictly dispersing billiards (Sinai billiards) have islands of effective stability, and hence are non-ergodic. The mechanism for creating the islands are corners of the billiard domain.Comment: 6 pages, 8 figures, submitted to Chao

Boost the Careers of Early-Stage Researchers

Boosting the careers of early-stage researchers at leading research-intensive universities of S&T occurs along highly competitive and selective mechanisms. Nurturing talent for careers in science is a primary concern and interest of the institutions (institutional perspective). In chapter two, we present five tools to boost the scientific careers of early-stage researchers within universities, i.e. research-based education, research master programmes, doctoral schools, guidance to postdoctoral researchers and tenure track.\ua0Most early-stage researchers move to careers outside universities (both research and nonresearch careers). That is why we address intersectoral mobility in chapter three and present\ua0dual career paths, business start-up support and permeability programmes as tools to boost\ua0the careers of researchers who will contribute to business and industry, public services, notfor-profit organisations and society at large (societal perspective). We also address recruitment of talent from outside academia (back) into our institutions.Transmission of transversal skills to early-stage researchers is essential to increase their employability and to make them attractive on the labour market (individual perspective). Since\ua0universities cannot predict which early-stage researcher will have what kind of career, both generic scientific skills and skills to increase employability are to be strengthened in parallel as\ua0described in chapter four.In chapter five, we introduce metrics as a well-established and indispensable tool in the recruitment, performance assessment and career development of early-stage researchers. We thereby differentiate between common HR metrics and next-generation metrics. The tricky question, of course, is how to safeguard the career perspectives of early-stage researchers while taking into account the reality of the wide-spread usage of some conventional andcontroversial metrics, such as publication in high impact journals.In chapter six, we address guidance and support measures for early-stage researchers.\ua0Universities need to offer career development tools, equal opportunities and family-friendly\ua0environment and infrastructure and support staff.While the chapters two to six contain our descriptions of the issues and present our findings\ua0on the tools, the final chapter seven contains concrete (hands-on) recommendations to department heads, HR professionals, university leaders and policy-makers and funders

A combined computational-experimental approach to define the structural origin of antibody recognition of sialyl-Tn, a tumor-associated carbohydrate antigen.

Anti-carbohydrate monoclonal antibodies (mAbs) hold great promise as cancer therapeutics and diagnostics. However, their specificity can be mixed, and detailed characterization is problematic, because antibody-glycan complexes are challenging to crystallize. Here, we developed a generalizable approach employing high-throughput techniques for characterizing the structure and specificity of such mAbs, and applied it to the mAb TKH2 developed against the tumor-associated carbohydrate antigen sialyl-Tn (STn). The mAb specificity was defined by apparent KD values determined by quantitative glycan microarray screening. Key residues in the antibody combining site were identified by site-directed mutagenesis, and the glycan-antigen contact surface was defined using saturation transfer difference NMR (STD-NMR). These features were then employed as metrics for selecting the optimal 3D-model of the antibody-glycan complex, out of thousands plausible options generated by automated docking and molecular dynamics simulation. STn-specificity was further validated by computationally screening of the selected antibody 3D-model against the human sialyl-Tn-glycome. This computational-experimental approach would allow rational design of potent antibodies targeting carbohydrates

Rumen cellulosomics : divergent fiber-degrading strategies revealed by comparative genome-wide analysis of six ruminococcal strains

Peer reviewedPublisher PD

Molecular Image Analysis: Quantitative Description and Classification of the Nuclear Lamina in Human Mesenchymal Stem Cells

The nuclear lamina is an intermediate filament network that provides a structural framework for the cell nucleus. Changes in lamina structure are found during changes in cell fate such as cell division or cell death and are associated with human diseases. An unbiased method that quantifies changes in lamina shape can provide information on cells undergoing changes in cellular functions. We have developed an image processing methodology that finds and quantifies the 3D structure of the nuclear lamina. We show that measurements on such images can be used for cell classification and provide information concerning protein spatial localization in this structure. To demonstrate the efficacy of this method, we compared the lamina of unmanipulated human mesenchymal stem cells (hMSCs) at passage 4 to cells activated for apoptosis. A statistically significant classification was found between the two populations

Robust nuclear lamina-based cell classification of aging and senescent cells

Changes in the shape of the nuclear lamina are exhibited in senescent cells, as well as in cells expressing mutations in lamina genes. To identify cells with defects in the nuclear lamina we developed an imaging method that quantifies the intensity and curvature of the nuclear lamina. We show that this method accurately describes changes in the nuclear lamina. Spatial changes in nuclear lamina coincide with redistribution of lamin A proteins and local reduction in protein mobility in senescent cell. We suggest that local accumulation of lamin A in the nuclear envelope leads to bending of the structure. A quantitative distinction of the nuclear lamina shape in cell populations was found between fresh and senescent cells, and between primary myoblasts from young and old donors. Moreover, with this method mutations in lamina genes were significantly distinct from cells with wild-type genes. We suggest that this method can be applied to identify abnormal cells during aging, in in vitro propagation, and in lamina disorders

Parabolic resonances and instabilities in near-integrable two degrees of freedom Hamiltonian flows

When an integrable two-degrees-of-freedom Hamiltonian system possessing a circle of parabolic fixed points is perturbed, a parabolic resonance occurs. It is proved that its occurrence is generic for one parameter families (co-dimension one phenomenon) of near-integrable, t.d.o. systems. Numerical experiments indicate that the motion near a parabolic resonance exhibits new type of chaotic behavior which includes instabilities in some directions and long trapping times in others. Moreover, in a degenerate case, near a {\it flat parabolic resonance}, large scale instabilities appear. A model arising from an atmospherical study is shown to exhibit flat parabolic resonance. This supplies a simple mechanism for the transport of particles with {\it small} (i.e. atmospherically relevant) initial velocities from the vicinity of the equator to high latitudes. A modification of the model which allows the development of atmospherical jets unfolds the degeneracy, yet traces of the flat instabilities are clearly observed

Complexity of the Ruminococcus flavefaciens FD-1 cellulosome reflects an expansion of family-related protein-protein interactions

This work was supported in part by the European Union, Area NMP.2013.1.1–2: Self-assembly of naturally occurring nanosystems: CellulosomePlus Project number: 604530, and by the EU Seventh Framework Programme (FP7 2007–2013) under the WallTraC project (Grant Agreement no 263916), and BioStruct-X (grant agreement no 283570). This paper reflects the author’s views only. The European Community is not liable for any use that may be made of the information contained herein. CMGAF is also supported by Fundação para a Ciência e a Tecnologia (Lisbon, Portugal) through grants PTDC/BIA-PRO/103980/2008 and EXPL/BIA-MIC/1176/2012. EAB is also funded by a grant (No. 1349/13) from the Israel Science Foundation (ISF), Jerusalem, Israel and by a grant (No. 2013284) from the U.S.-Israel Binational Science Foundation (BSF). E.A.B. is the incumbent of The Maynard I. and Elaine Wishner Chair of Bio-organic Chemistry.Peer reviewedPublisher PD

Gram-Negative Bacteremia upon Hospital Admission: When Should Pseudomonas aeruginosa Be Suspected?

Background. Pseudomonas aeruginosa is an uncommon cause of community-acquired bacteremia among patients without severe immunodeficiency. Because tension exists between the need to limit unnecessary use of anti-pseudomonal agents and the need to avoid a delay in appropriate therapy, clinicians require better guidance regarding when to cover empirically for P. aeruginosa. We sought to determine the occurrence of and construct a model to predict P. aeruginosa bacteremia upon hospital admission. Methods. A retrospective study was conducted in 4 tertiary care hospitals. Microbiology databases were searched to find all episodes of bacteremia caused by gram-negative rods (GNRs) ⩽48 h after hospital admission. Patient data were extracted from the medical records of 151 patients with P. aeruginosa bacteremia and of 152 randomly selected patients with bacteremia due to Enterobacteriaceae. Discriminative parameters were identified using logistic regression, and the probabilities of having P. aeruginosa bacteremia were calculated. Results. P. aeruginosa caused 6.8% of 4114 unique patient episodes of GNR bacteremia upon hospital admission (incidence ratio, 5 cases per 10,000 hospital admissions). Independent predictors of P. aeruginosa bacteremia were severe immunodeficiency, age >90 years, receipt of antimicrobial therapy within past 30 days, and presence of a central venous catheter or a urinary device. Among 250 patients without severe immunodeficiency, if no predictor variables existed, the likelihood of having P. aeruginosa bacteremia was 1:42. If ⩾2 predictors existed, the risk increased to nearly 1:3. Conclusions. P. aeruginosa bacteremia upon hospital admission in patients without severe immunodeficiency is rare. Among immunocompetent patients with suspected GNR bacteremia who have ⩾2 predictors, empirical anti-pseudomonal treatment is warrante