Massively Parallel Interrogation of Aptamer Sequence, Structure and Function

BACKGROUND: Optimization of high affinity reagents is a significant bottleneck in medicine and the life sciences. The ability to synthetically create thousands of permutations of a lead high-affinity reagent and survey the properties of individual permutations in parallel could potentially relieve this bottleneck. Aptamers are single stranded oligonucleotides affinity reagents isolated by in vitro selection processes and as a class have been shown to bind a wide variety of target molecules. METHODOLOGY/PRINCIPAL FINDINGS: High density DNA microarray technology was used to synthesize, in situ, arrays of approximately 3,900 aptamer sequence permutations in triplicate. These sequences were interrogated on-chip for their ability to bind the fluorescently-labeled cognate target, immunoglobulin E, resulting in the parallel execution of thousands of experiments. Fluorescence intensity at each array feature was well resolved and shown to be a function of the sequence present. The data demonstrated high intra- and inter-chip correlation between the same features as well as among the sequence triplicates within a single array. Consistent with aptamer mediated IgE binding, fluorescence intensity correlated strongly with specific aptamer sequences and the concentration of IgE applied to the array. CONCLUSION AND SIGNIFICANCE: The massively parallel sequence-function analyses provided by this approach confirmed the importance of a consensus sequence found in all 21 of the original IgE aptamer sequences and support a common stem:loop structure as being the secondary structure underlying IgE binding. The microarray application, data and results presented illustrate an efficient, high information content approach to optimizing aptamer function. It also provides a foundation from which to better understand and manipulate this important class of high affinity biomolecules

Unfrustrated Qudit Chains and their Ground States

We investigate chains of 'd' dimensional quantum spins (qudits) on a line with generic nearest neighbor interactions without translational invariance. We find the conditions under which these systems are not frustrated, i.e. when the ground states are also the common ground states of all the local terms in the Hamiltonians. The states of a quantum spin chain are naturally represented in the Matrix Product States (MPS) framework. Using imaginary time evolution in the MPS ansatz, we numerically investigate the range of parameters in which we expect the ground states to be highly entangled and find them hard to approximate using our MPS method.Comment: 5 pages, 5 figures. Typos correcte

Bioinspired polydimethylsiloxane-based composites with high shear resistance against wet tissue

Patterned microstructures represent a potential approach for improving current wound closure strategies. Microstructures can be fabricated by multiple techniques including replica molding of soft polymer-based materials. However, polymeric microstructures often lack the required shear resistance with tissue needed for wound closure. In this work, scalable microstructures made from composites based on polydimethylsiloxane (PDMS) were explored to enhance the shear resistance with wet tissue. To achieve suitable mechanical properties, PDMS was reinforced by incorporation of polyethylene (PE) particles into the pre-polymer and by coating PE particle reinforced substrates with parylene. The reinforced microstructures showed a 6-fold enhancement, the coated structures even a 13-fold enhancement in Young׳s modulus over pure PDMS. Shear tests of mushroom-shaped microstructures (diameter 450 µm, length 1 mm) against chicken muscle tissue demonstrate first correlations that will be useful for future design of wound closure or stabilization implants

Quantum entanglement between electronic and vibrational degrees of freedom in molecules

We consider the quantum entanglement of the electronic and vibrational degrees of freedom in molecules with a tendency towards double welled potentials using model coupled harmonic diabatic potential-energy surfaces. The von Neumann entropy of the reduced density matrix is used to quantify the electron-vibration entanglement for the lowest two vibronic wavefunctions in such a bipartite system. Significant entanglement is found only in the region in which the ground vibronic state contains a density profile that is bimodal (i.e., contains two separate local minima). However, in this region two distinct types of entanglement are found: (1) entanglement that arises purely from the degeneracy of energy levels in the two potential wells and which is destroyed by slight asymmetry, and (2) entanglement that involves strongly interacting states in each well that is relatively insensitive to asymmetry. These two distinct regions are termed fragile degeneracy-induced entanglement and persistent entanglement, respectively. Six classic molecular systems describable by two diabatic states are considered: ammonia, benzene, semibullvalene, pyridine excited triplet states, the Creutz-Taube ion, and the radical cation of the "special pair" of chlorophylls involved in photosynthesis. These chemically diverse systems are all treated using the same general formalism and the nature of the entanglement that they embody is elucidated

Kepler Eclipsing Binary Stars. VI. Identification of Eclipsing Binaries in the K2 Campaign 0 Data-set

The original {\it Kepler} mission observed and characterized over 2400 eclipsing binaries in addition to its prolific exoplanet detections. Despite the mechanical malfunction and subsequent non-recovery of two reaction wheels used to stabilize the instrument, the {\it Kepler} satellite continues collecting data in its repurposed {\it K2} mission surveying a series of fields along the ecliptic plane. Here we present an analysis of the first full baseline {\it K2} data release: the Campaign 0 data-set. In the 7761 light curves, we have identified a total of 207 eclipsing binaries. Of these, 97 are new discoveries that were not previously identified. Our pixel-level analysis of these objects has also resulted in identification of several false positives (observed targets contaminated by neighboring eclipsing binaries), as well as the serendipitous discovery of two short period exoplanet candidates. We provide catalog cross-matched source identifications, orbital periods, morphologies and ephemerides for these eclipsing systems. We also describe the incorporation of the K2 sample into the Kepler Eclipsing Binary Catalog\footnote{\url{keplerebs.villanova.edu/k2}}, present spectroscopic follow-up observations for a limited selection of nine systems, and discuss prospects for upcoming {\it K2} campaigns.Comment: Accepted for publication in MNRAS. 51 pages [20 figures, 8 tables]. Results available online in the Kepler Eclipsing Binary Star Catalog http://keplerebs.villanova.edu/k

Bimodal Mesoporous Titanium Nitride/Carbon Microfibers as Efficient and Stable Electrocatalysts for Li–O_2 Batteries

The rechargeable Li–O_2 battery has been considered as a sustainable chemical power source for electric vehicles and grid energy storage systems due to the high theoretical specific energy (∼3500 Wh/kg). The practical performance of Li–O_2 batteries is, however, still far below expectations. This is mainly attributed to the (1) intrinsic sluggish reaction kinetics of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), (2) passivation of the electrodes by electrical isolation and pore blocking, and (3) chemical instability of the organic cell components, i.e., electrolyte, polymer binder, and carbon electrode, in the presence of O_2•– and Li_2O_2. It is crucial to develop highly porous, three-dimensional, conducting cathode catalyst/gas diffusion layer (GDL) architectures possessing superior catalytic activity and stability with respect to the ORR and the OER in order to address these issues. All of these requirements prompted us to examine the catalytic performance of porous framework metal nitride electrodes for Li–O_2 batteries

Gonadotropin-releasing hormone increased pregnancy risk in suckled beef cows not detected in estrus and subjected to a split-time artificial insemination program

Citation: Hill, S. L., Grieger, D. M., Olson, K. C., Jaeger, J. R., Dahlen, C. R., Crosswhite, M. R., . . . Stevenson, J. S. (2016). Gonadotropin-releasing hormone increased pregnancy risk in suckled beef cows not detected in estrus and subjected to a split-time artificial insemination program. Journal of Animal Science, 94(9), 3722-3728. doi:10.2527/jas2016-0582We hypothesized that GnRH would increase pregnancy risk (PR) in a split-time AI program for cows in which estrus was not detected. A total of 1,236 suckled beef cows at 12 locations in 3 states (Colorado, Kansas, and North Dakota) were enrolled. Before applying the fixed-time AI program, BCS was assessed. Cows were treated on d -7 with a progesterone insert concurrent with 100 mu g GnRH and on d 0 with 25 mg PGF(2 alpha) plus removal of the insert. Estrus-detection patches were affixed to cows at insert removal. Estrus was defined to have occurred when an estrus-detection patch was >50% colored (activated). Cows in estrus by 65 h (n = 758; 61.3% of all cows) were randomly allocated to 2 treatments: 1) 100 mu g GnRH and early + GnRH (E+G; n = 373) or 2) AI only at 65 h (early -no GnRH [E-G]; n = 385). The remaining cows were randomly allocated to 2 treatments: 1) 5(L+G; n = 252) or 2) AI only at 84 h (late no GnRH [L-G]; n = 226). Pregnancy was determined 35 d after AI via transrectal ultrasound. Pregnancy risk did not differ (P = 0.68) between E+G and E-G cows (61.9 vs. 60.4%, respectively). Conversely, for cows inseminated at 84 h, PR was greater (P = 0.01) in cows that received GnRH (L+G) compared with their herd mates not receiving GnRH (L-G; 41.7 vs. 30.8%, respectively). Of those cows not detected in estrus by 65 h, 42.1% were detected by 84 h, for a total expression of estrus by all cows of 77.6%. Administration of GnRH increased (P < 0.01) PR in cows not detected in estrus by 84 h (+ GnRH = 33.4% [n = 146] vs. no GnRH = 15.0% [n = 128]) but had no effect in cows expressing estrus by 84 h (+ GnRH = 65.3% [n = 103] vs. no GnRH = 61.7% [n = 97]). Neither estrus expression by 65 or 84 h nor PR was influenced by BCS, parity, or days postpartum at AI. Cows had greater PR when they had been detected in estrus before AI, and PR was improved by administration of GnRH at 65 h after insert removal in cows that were not detected in estrus and inseminated at 84 h