1,137 research outputs found
AFM pulling and the folding of donor-acceptor oligorotaxanes: phenomenology and interpretation
The thermodynamic driving force in the self-assembly of the secondary
structure of a class of donor-acceptor oligorotaxanes is elucidated by means of
molecular dynamics simulations of equilibrium isometric single-molecule force
spectroscopy AFM experiments. The oligorotaxanes consist of
cyclobis(paraquat-\emph{p}-phenylene) rings threaded onto an oligomer of
1,5-dioxynaphthalenes linked by polyethers. The simulations are performed in a
high dielectric medium using MM3 as the force field. The resulting force vs.
extension isotherms show a mechanically unstable region in which the molecule
unfolds and, for selected extensions, blinks in the force measurements between
a high-force and a low-force regime. From the force vs. extension data the
molecular potential of mean force is reconstructed using the weighted histogram
analysis method and decomposed into energetic and entropic contributions. The
simulations indicate that the folding of the oligorotaxanes is energetically
favored but entropically penalized, with the energetic contributions overcoming
the entropy penalty and effectively driving the self-assembly. In addition, an
analogy between the single-molecule folding/unfolding events driven by the AFM
tip and the thermodynamic theory of first-order phase transitions is discussed
and general conditions, on the molecule and the cantilever, for the emergence
of mechanical instabilities and blinks in the force measurements in equilibrium
isometric pulling experiments are presented. In particular, it is shown that
the mechanical stability properties observed during the extension are
intimately related to the fluctuations in the force measurements.Comment: 42 pages, 17 figures, accepted to the Journal of Chemical Physic
A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow
© 2016 Author(s). The study of inflammatory bowel disease, including Ulcerative Colitis and Crohn's Disease, has relied largely upon the use of animal or cell culture models; neither of which can represent all aspects of the human pathophysiology. Presented herein is a dual flow microfluidic device which holds full thickness human intestinal tissue in a known orientation. The luminal and serosal sides are independently perfused ex vivo with nutrients with simultaneous waste removal for up to 72 h. The microfluidic device maintains the viability and integrity of the tissue as demonstrated through Haematoxylin & Eosin staining, immunohistochemistry and release of lactate dehydrogenase. In addition, the inflammatory state remains in the tissue after perfusion on the device as determined by measuring calprotectin levels. It is anticipated that this human model will be extremely useful for studying the biology and tes ting novel interventions in diseased tissue
Steric constraints in model proteins
A simple lattice model for proteins that allows for distinct sizes of the
amino acids is presented. The model is found to lead to a significant number of
conformations that are the unique ground state of one or more sequences or
encodable. Furthermore, several of the encodable structures are highly
designable and are the non-degenerate ground state of several sequences. Even
though the native state conformations are typically compact, not all compact
conformations are encodable. The incorporation of the hydrophobic and polar
nature of amino acids further enhances the attractive features of the model.Comment: RevTex, 5 pages, 3 postscript figure
Career planning courses increase career readiness of graduate and postdoctoral trainees
BACKGROUND: Given national calls for intentional career development during graduate and post-graduate scientific training, this study assessed career readiness development within the context of academic career courses. The current study evaluated the effects of academic career courses offered at two institutions that were specifically designed to increase career awareness, interest, and career-related confidence among doctoral students and postdoctoral fellows.
METHODS: Participants enrolled in a career course at trainees' respective academic institutions and responded to pre- and post-course surveys (n=32, n=148). The paper offers a thematic analysis of each of the two courses using an individualized learning plan career development framework and describes the results of their respective pretest-posttest evaluations which indicated increases in career readiness. RESULTS: Though the format and content provided in each course varied, participation was associated with increases in career readiness. Participants reported increased career-awareness including a greater familiarity with different types of careers overall. Furthermore, interest in tenure track faculty careers increased in both samples, which may assuage fears that exposure to diverse career pathways could reduce interest in academic careers. Transferrable skills, including career planning and awareness also significantly increased. Course participants reported an increase in the number and type of mentors they interacted with beyond their principal faculty mentor (other faculty, professional PhDs, peers, and administrative staff).
CONCLUSIONS: Findings provide supporting evidence for the benefits of implementing structured career development efforts during PhD training; even with varying content, delivery methods, and instructor type, both academic career courses led to significant gains in career awareness and readiness. Successful development and delivery of academic career courses, with a focus on career planning skills, suggest that institutions can utilize these and are an effective way to prepare PhDs for their transition from training positions into careers.DP7 OD020317 - NIH HHS; P20 GM121327 - NIGMS NIH HHS; P30 CA177558 - NCI NIH HHS; R01 GM140282 - NIGMS NIH HHSPublished versio
Surface Enhanced Second Harmonic Generation from Macrocycle, Catenane, and Rotaxane Thin Films: Experiments and Theory
Surface enhanced second harmonic generation (SE SHG) experiments on molecular structures, macrocycles, catenanes, and rotaxanes, deposited as monolayers and multilayers by vacuum sublimation on silver, are reported. The measurements show that the molecules form ordered thin films, where the highest degree of order is observed in the case of macrocycle monolayers and the lowest in the case of rotaxane multilayers. The second harmonic generation activity is interpreted in terms of electric field induced second harmonic (EFISH) generation where the electric field is created by the substrate silver atoms. The measured second order nonlinear optical susceptibility for a rotaxane thin film is compared with that obtained by considering only EFISH contribution to SHG intensity. The electric field on the surface of a silver layer is calculated by using the Delphi4 program for structures obtained with TINKER molecular mechanics/dynamics simulations. An excellent agreement is observed between the calculated and the measured SHG susceptibilities.
52. Development of network of cancer family syndrome registries in eastern Europe
It has been proven that organizing the registries of families affected by CFS is very helpful in research leading to: 1. Identification of new genes of CFS, 2. Better knowledge of correlations in CFS, 3. Identification of external factors having impact on mutated genes, 4. Description of mutation characteristic for particular populations.Thus, development of CFS registries is very important for increasing pre-clinical and clinical research facilities. Direct positive consequence will also be the improvement of quality of life by better management of patients affected by CFS. Without registries these patients are very often not identified and deprived of appropriate recommendations concerning prophylactics, surveillance and treatment. Development of CFS registries leads also to further improvement of quality of life by progress in management in families with these tumours which can be achieved by better organizing of research on CFS. Better management in CFS families decreases also health-care costs by lowering the number of cancers and increasing the number of tumours detected at their earliest clinical stage when the treatment is less expensive.The scientific objectives of the project include:-elaboration of standards for a model cancer family syndrome registries in Eastern Europe-registration of ∼ 2000 families with different types of CFS in populations of East European countries (Czech, Hungary, Latvia, Lithuania, Poland)-initiation of European collaborative studies with the use of material collected by East European CFS registries
Supernova Remnants as Clues to Their Progenitors
Supernovae shape the interstellar medium, chemically enrich their host
galaxies, and generate powerful interstellar shocks that drive future
generations of star formation. The shock produced by a supernova event acts as
a type of time machine, probing the mass loss history of the progenitor system
back to ages of 10 000 years before the explosion, whereas supernova
remnants probe a much earlier stage of stellar evolution, interacting with
material expelled during the progenitor's much earlier evolution. In this
chapter we will review how observations of supernova remnants allow us to infer
fundamental properties of the progenitor system. We will provide detailed
examples of how bulk characteristics of a remnant, such as its chemical
composition and dynamics, allow us to infer properties of the progenitor
evolution. In the latter half of this chapter, we will show how this exercise
may be extended from individual objects to SNR as classes of objects, and how
there are clear bifurcations in the dynamics and spectral characteristics of
core collapse and thermonuclear supernova remnants. We will finish the chapter
by touching on recent advances in the modeling of massive stars, and the
implications for observable properties of supernovae and their remnants.Comment: A chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and
Paul Murdin (18 pages, 6 figures
An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints
In this work, we introduce an algorithm to compute the derivatives of
physical observables along the constrained subspace when flexible constraints
are imposed on the system (i.e., constraints in which the hard coordinates are
fixed to configuration-dependent values). The presented scheme is exact, it
does not contain any tunable parameter, and it only requires the calculation
and inversion of a sub-block of the Hessian matrix of second derivatives of the
function through which the constraints are defined. We also present a practical
application to the case in which the sought observables are the Euclidean
coordinates of complex molecular systems, and the function whose minimization
defines the constraints is the potential energy. Finally, and in order to
validate the method, which, as far as we are aware, is the first of its kind in
the literature, we compare it to the natural and straightforward
finite-differences approach in three molecules of biological relevance:
methanol, N-methyl-acetamide and a tri-glycine peptideComment: 13 pages, 8 figures, published versio
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