Magnetic Micromotors for Multiple Motile Sperm Cells Capture,Transport, and Enzymatic Release

An integrated system combining a magnetically-driven micromotor and a synthetized protein-based hyaluronic acid (HA) microflake is presented for the in situ selection and transport of multiple motile sperm cells (ca. 50). The system appeals for targeted sperm delivery in the reproductive system to assist fertilization or to deliver drugs. The binding mechanism between the HA microflake and sperm relies on the interactions between HA and the corresponding sperm HA receptors. Once sperm are captured within the HA microflake, the assembly is trapped and transported by a magnetically-driven helical microcarrier. The trapping of the sperm-microflake occurs by a local vortex induced by the microcarrier during rotation-translation under a rotating magnetic field. After transport, the microflake is enzymatically hydrolyzed by local proteases, allowing sperm to escape and finally reach the target location. This cargo-delivery system represents a new concept to transport not only multiple motile sperm but also other actively moving biological cargoes.     

Dynamics of Bacteriorhodopsin in the Dark-Adapted State from Solution Nuclear Magnetic Resonance Spectroscopy

To achieve efficient proton pumping in the light-driven proton pump bacteriorhodopsin (bR), the protein must be tightly coupled to the retinal to rapidly convert retinal isomerization into protein structural rearrangements. Methyl group dynamics of bR embedded in lipid nanodiscs were determined in the dark-adapted state, and were found to be mostly well ordered at the cytosolic side. Methyl groups in the M145A mutant of bR, which displays only 10 % residual proton pumping activity, are less well ordered, suggesting a link between side-chain dynamics on the cytosolic side of the bR cavity and proton pumping activity. In addition, slow conformational exchange, attributed to low frequency motions of aromatic rings, was indirectly observed for residues on the extracellular side of the bR cavity. This may be related to reorganization of the water network. These observations provide a detailed picture of previously undescribed equilibrium dynamics on different time scales for ground-state bR.     

On the use of AES data analysis to determine local enrichments of conversion coating elements at intermetallic particles on rolled Al

In this paper, the behaviour of the industrial applied Ti/Zr conversion coating (CC) pretreatment on rolled automotive aluminium samples (AA5182) is analysed. Due to its nanometre lateral and depth resolution, Auger electron spectroscopy (AES) is used to analyse the CC distribution at surface cathodic intermetallic particles. As a result of its high surface sensitivity, the AES technique is very susceptible to differences in the top contamination layer thickness. It is demonstrated that AES point measurements performed on aluminium model samples coated with 1.5 and 3 nm of Ti (oxide) layer cannot differentiate the two-layer thicknesses if a difference in the top contamination thickness is not taken into account. A data analysis methodology is introduced, based on the ratio of normalized peak areas (enrichment ratios), to eliminate the effect of the contamination layer thickness. The experimental validation of the methodology is performed on the model samples, demonstrating errors of 2% on the enrichment ratios on similar samples with different contamination layer thicknesses, while the conventional spectra quantification results in errors of 49%. The methodology is also theoretically substantiated within certain constraints. By the use of the AES methodology, an enriched Ti and Zr deposition is confirmed at the cathodic intermetallic particles at the surface of the industrial no-rinse CC sprayed automotive aluminium sheet samples.     

Benchtop NMR analysis of piperazine-based drugs hyperpolarised by SABRE

Piperazine-based drugs, such as N-benzylpiperazine (BZP), became attractive in the 2000s due to possessing effects similar to amphetamines. Herein, BZP, in addition to its pyridyl analogues, 2-, 3-, and 4-pyridylmethylpiperidine (2-PMP, 3-PMP, and 4-PMP respectively) was subjected to the hyperpolarisation technique Signal Amplification By Reversible Exchange (SABRE) in order to demonstrate the use of this technique to detect these piperazine-based drugs. Although BZP was not hyperpolarised via SABRE, 2-PMP, 3-PMP, and 4-PMP were, with the ortho- and meta-pyridyl protons of 4-PMP showing the largest enhancement of 313-fold and 267-fold, respectively, in a 1.4-T detection field, following polarisation transfer at Earth's magnetic field. In addition to the freebase, 4-PMP.3HCl was also appraised by SABRE and was found not to polarise, however, the addition of increasing equivalents of triethylamine (TEA) produced the freebase, with a maximum enhancement observed upon the addition of 3 equivalents of TEA. Further addition of TEA led to a reduction in the observed enhancement. SABRE was also employed to polarise 4-PMP.3HCl (~20% w/w) in a simulated tablet to demonstrate the forensic application of the technique (138-fold enhancement for the ortho-pyridyl protons). The amount of 4-PMP.3HCl present in the simulated tablet was quantified via NMR using D₂O as a solvent and compared well to complimentary gas chromatography–mass spectrometry data. Exchanging D₂O for CD₃OD as the solvent utilised for analysis resulted in a significantly lower amount of 4-PMP.3HCl being determined, thus highlighting safeguarding issues linked to drug abuse in relation to determining the amount of active pharmaceutical ingredient present.     

Highly Conjugated π-Systems Arising from Cannibalistic Hexadehydro-Diels–Alder Couplings: Cleavage of C−C Single and Triple Bonds

We have investigated the cannibalistic self-trapping reaction of an ortho-benzyne derivative generated from 1,11-bis(p-tolyl)undeca-1,3,8,10-tetrayne in an HDDA reaction. Without adding any specific trapping agent, the highly reactive benzyne is trapped by another bisdiyne molecule in at least three different modes. We have isolated and characterized the resulting products and performed high-level calculations concerning the reaction mechanism. During the cannibalistic self-trapping process, either a C≡C triple bond or an sp–sp³ C−C single bond is cleaved. Up to seven rings and nine C−C bonds are formed starting from two 1,11-bis(p-tolyl)undeca-1,3,8,10-tetrayne molecules. Our experiments and calculations provide considerable insight into the variety of reaction pathways which the ortho-benzyne derivative, generated from a bisdiyne, can take when reacting with another bisdiyne molecule.     

On sums of powers of inverse complete quotients

For an irrational number , let denote its -th continued fraction inverse complete quotient, obtained by deleting the first partial quotients. For any positive real number , we establish the optimal linear bound on the sum of the -th powers of the first complete quotients. That is, we find the smallest constants such that for all and all irrationals .

     

Rational approximation of vertical segments

In many applications, observations are prone to imprecise measurements. When constructing a model based on such data, an approximation rather than an interpolation approach is needed. Very often a least squares approximation is used. Here we follow a different approach. A natural way for dealing with uncertainty in the data is by means of an uncertainty interval. We assume that the uncertainty in the independent variables is negligible and that for each observation an uncertainty interval can be given which contains the (unknown) exact value. To approximate such data we look for functions which intersect all uncertainty intervals. In the past this problem has been studied for polynomials, or more generally for functions which are linear in the unknown coefficients. Here we study the problem for a particular class of functions which are nonlinear in the unknown coefficients, namely rational functions. We show how to reduce the problem to a quadratic programming problem with a strictly convex objective function, yielding a unique rational function which intersects all uncertainty intervals and satisfies some additional properties. Compared to rational least squares approximation which reduces to a nonlinear optimization problem where the objective function may have many local minima, this makes the new approach attractive.