The Successful Relaunch of Scientia Pharmaceutica Continues Achieving Success

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Macromolecular structural dynamics visualized by pulsed dose control in 4D electron microscopy

Macromolecular conformation dynamics, which span a wide range of time scales, are fundamental to the understanding of properties and functions of their structures. Here, we report direct imaging of structural dynamics of helical macromolecules over the time scales of conformational dynamics (ns to subsecond) by means of four-dimensional (4D) electron microscopy in the single-pulse and stroboscopic modes. With temporally controlled electron dosage, both diffraction and real-space images are obtained without irreversible radiation damage. In this way, the order-disorder transition is revealed for the organic chain polymer. Through a series of equilibrium-temperature and temperature-jump dependencies, it is shown that the metastable structures and entropy of conformations can be mapped in the nonequilibrium region of a “funnel-like” free-energy landscape. The T-jump is introduced through a substrate (a “hot plate” type arrangement) because only the substrate is made to absorb the pulsed energy. These results illustrate the promise of ultrafast 4D imaging for other applications in the study of polymer physics as well as in the visualization of biological phenomena

The Bubble Bursts: The 2015 Opt-Out Movement in New Jersey

The Bubble Bursts: The 2015 Opt-Out Movement in New Jersey analyzes the scope, factors, and context of the opt-out movement that occurred in New Jersey in the spring of 2015. Using test participation data released in February 2016 by the New Jersey Department of Education, we found that approximately 135,000 students did not take the state assessment in the spring of 2015. Depending on how it was calculated, this represented between 11-19% of the population of students eligible for testing in grades 3 to 11 in the state. There was also a positive correlation between higher district opt-out rates and wealthier districts. We found that several factors contributed to these trends. Predominant amongst these were an accumulated skepticism with high stakes testing in general and the new PARCC assessment in particular, concerns from the Common Core State Standards rollout, teacher union opposition to premature teacher accountability, and confusion in the messages of state policymakers about graduation requirements. These explanatory factors were based upon interviews with over 30 state policymakers, professional education association representatives, advocacy group leaders, school administrators, teachers, parents, and students

The Bubble Bursts: The 2015 Opt-Out Movement in New Jersey

"The Bubble Bursts: The 2015 Opt-Out Movement in New Jersey" analyzes the scope, factors, and context of the opt-out movement that occurred in New Jersey in the spring of 2015. Using test participation data released in February 2016 by the New Jersey Department of Education, we found that approximately 135,000 students did not take the state assessment in the spring of 2015. Depending on how it was calculated, this represented between 11-19% of the population of students eligible for testing in grades 3 to 11 in the state. There was also a positive correlation between higher district opt-out rates and wealthier districts. We found that several factors contributed to these trends. Predominant amongst these were an accumulated skepticism with high stakes testing in general and the new PARCC assessment in particular, concerns from the Common Core State Standards rollout, teacher union opposition to premature teacher accountability, and confusion in the messages of state policymakers about graduation requirements. These explanatory factors were based upon interviews with over 30 state policymakers, professional education association representatives, advocacy group leaders, school administrators, teachers, parents, and students

Microsecond folding dynamics of the F13W G29A mutant of the B domain of staphylococcal protein A by laser-induced temperature jump

The small size (58 residues) and simple structure of the B domain of staphylococcal protein A (BdpA) have led to this domain being a paradigm for theoretical studies of folding. Experimental studies of the folding of BdpA have been limited by the rapidity of its folding kinetics. We report the folding kinetics of a fluorescent mutant of BdpA (G29A F13W), named F13W*, using nanosecond laser-induced temperature jump experiments. Automation of the apparatus has permitted large data sets to be acquired that provide excellent signal-to-noise ratio over a wide range of experimental conditions. By measuring the temperature and denaturant dependence of equilibrium and kinetic data for F13W*, we show that thermodynamic modeling of multidimensional equilibrium and kinetic surfaces is a robust method that allows reliable extrapolation of rate constants to regions of the folding landscape not directly accessible experimentally. The results reveal that F13W* is the fastest-folding protein of its size studied to date, with a maximum folding rate constant at 0 M guanidinium chloride and 45°C of 249,000 (s-1). Assuming the single-exponential kinetics represent barrier-limited folding, these data limit the value for the preexponential factor for folding of this protein to at least ≈2 x 10(6) s(-1)

Optimum spectral window for imaging of art with optical coherence tomography

Optical Coherence Tomography (OCT) has been shown to have potential for important applications in the field of art conservation and archaeology due to its ability to image subsurface microstructures non-invasively. However, its depth of penetration in painted objects is limited due to the strong scattering properties of artists’ paints. VIS-NIR (400 nm – 2400 nm) reflectance spectra of a wide variety of paints made with historic artists’ pigments have been measured. The best spectral window with which to use optical coherence tomography (OCT) for the imaging of subsurface structure of paintings was found to be around 2.2 μm. The same spectral window would also be most suitable for direct infrared imaging of preparatory sketches under the paint layers. The reflectance spectra from a large sample of chemically verified pigments provide information on the spectral transparency of historic artists’ pigments/paints as well as a reference set of spectra for pigment identification. The results of the paper suggest that broadband sources at ~2 microns are highly desirable for OCT applications in art and potentially material science in general

Ab initio theory of helix-coil phase transition

In this paper we suggest a theoretical method based on the statistical mechanics for treating the alpha-helix-random coil transition in alanine polypeptides. We consider this process as a first-order phase transition and develop a theory which is free of model parameters and is based solely on fundamental physical principles. It describes essential thermodynamical properties of the system such as heat capacity, the phase transition temperature and others from the analysis of the polypeptide potential energy surface calculated as a function of two dihedral angles, responsible for the polypeptide twisting. The suggested theory is general and with some modification can be applied for the description of phase transitions in other complex molecular systems (e.g. proteins, DNA, nanotubes, atomic clusters, fullerenes).Comment: 24 pages, 3 figure

Multiplex cytokine profile from dengue patients: MIP-1beta and IFN-gamma as predictive factors for severity

<p>Abstract</p> <p>Background</p> <p>Dengue virus pathogenesis is not yet fully understood and the identification of patients at high risk for developing severe disease forms is still a great challenge in dengue patient care. During the present study, we evaluated prospectively the potential of cytokines present in plasma from patients with dengue in stratifying disease severity.</p> <p>Methods</p> <p>Seventeen-cytokine multiplex fluorescent microbead immunoassay was used for the simultaneous detection in 59 dengue patients. GLM models using bimodal or Gaussian family were determined in order to associate cytokines with clinical manifestations and laboratory diagnosis.</p> <p>Results</p> <p>IL-1β, IFN-γ, IL-4, IL-6, IL-13, IL-7 and GM-CSF were significantly increased in patients with severe clinical manifestations (severe dengue) when compared to mild disease forms (mild dengue). In contrast, increased MIP-1β levels were observed in patients with mild dengue. MIP-1β was also associated with CD56+NK cell circulating rates. IL-1β, IL-8, TNF-α and MCP-1 were associated with marked thrombocytopenia. Increased MCP-1 and GM-CSF levels correlated with hypotension. Moreover, MIP-1β and IFN-γ were independently associated with both dengue severity and disease outcome.</p> <p>Conclusion</p> <p>Our data demonstrated that the use of a multiple cytokine assay platform was suitable for identifying distinct cytokine profiles associated with the dengue clinical manifestations and severity. MIP-β is indicated for the first time as a good prognostic marker in contrast to IFN-γ that was associated with disease severity.</p

Advances in multispectral and hyperspectral imaging for archaeology and art conservation

Multispectral imaging has been applied to the field of art conservation and art history since the early 1990s. It is attractive as a noninvasive imaging technique because it is fast and hence capable of imaging large areas of an object giving both spatial and spectral information. This paper gives an overview of the different instrumental designs, image processing techniques and various applications of multispectral and hyperspectral imaging to art conservation, art history and archaeology. Recent advances in the development of remote and versatile multispectral and hyperspectral imaging as well as techniques in pigment identification will be presented. Future prospects including combination of spectral imaging with other noninvasive imaging and analytical techniques will be discussed