Development and Validation of an LC-MS/MS Method for Simultaneous Determination of Short Peptide-Based Drugs in Human Blood Plasma

A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The developed method was successfully applied to pharmacokinetic studies. The sample preparation process included solid-phase extraction (SPE). Effective chromatographic separation of the analytes and internal standard (dalargin) was achieved with a C18 column, using a gradient elution with two mobile phases: 0.1% v/v formic acid (aqueous solution) and 0.1% v/v formic acid (acetonitrile solution). The linearity of the method was demonstrated within a concentration range of 0.5–20 ng/mL, with correlation coefficients between 0.998–0.999 for goserelin, buserelin, triptorelin, and octreotide, respectively. The relative standard deviation (RSD, %) values for method accuracy and precision did not exceed 20% at the lower level of quantitation (LLOQ) or 15% at other concentration levels.     

Coverings of random ellipsoids,and invertibility of matrices with i.i.d. heavy-tailed entries

Let A = (a_ij) be an n × n random matrix with i.i.d. entries such that Ea₁₁ = 0 and Ea ₁₁ ² = 1. We prove that for any δ > 0 there is L > 0 depending only on δ, and a subset N of B ₂ ⁿ of cardinality at most exp(δn) such that with probability very close to one we have

$$A\left( {B_2^n} \right)\subset\mathop \cup \limits_{y \in A\left( \mathcal{N} \right)} \left( {y + L\sqrt n B_2^n} \right)$$

. In fact, a stronger statement holds true. As an application, we show that for some L' > 0 and u ∈ [0, 1) depending only on the distribution law of a11, the smallest singular value sn of the matrix A satisfies

$$\mathbb{P}\left\{ {{s_n}\left( A \right) \leq \varepsilon {n^{ - 1/2}}} \right\} \leq L'\varepsilon + {u^n}$$

for all ε > 0. The latter result generalizes a theorem of Rudelson and Vershynin which was proved for random matrices with subgaussian entries.

     

Mechanical Unfolding of a Homopolymer Globule: Applied Force versus Applied Deformation

We propose the quantitative mean-field theory of mechanical unfolding of a globule formed by long flexible homopolymer chain collapsed in poor solvent and subjected to an extensional force We show that with an increase in the applied force the globule unfolds as a whole without formation of an intermediate state. The value of the threshold force and the corresponding jump in the distance between chain ends increase with a deterioration of the solvent quality and / or with an increase in the degree of polymerization. This way of globule unfolding is compared with that in the D-ensemble, when the distance between chain ends is imposed.     

Self-assembled silver nanoparticles in glass microstructured by poling for SERS application

A simple technique to fabricate microchannels in glasses with self-assembled silver nanoparticles (NPs) in the channels is presented. It combines thermal-electric poling of silver-to-sodium ion-exchanged glass slides with a patterned anodic electrode, formation of the microchannels via selective etching off the unpoled slide regions, and hydrogen annealing. The annealing results in the growth of NPs only on the bottom of the channels. The studies performed allowed optimizing the channels’ depth and NPs surface density for Surface Enhanced Raman Scattering (SERS) based sensing and microfluidic applications. We have demonstrated that the formed NPs allow detection of 1/20 of BPE (1,2-Di(4-pyridyl)ethylene 97%) monolayer, the evaluated Raman enhancement factor being ~4·10⁷. The proposed approach based on the glass poling allowed us the fabrication of ~1 μm deep channels and easy multiplication of the structures because the anodic electrodes used for the poling are capable of multiple usage.     

Synthesis of pyrrolo[2,3-c]2,7-naphthyridine derivatives by cascade heterocyclization reaction of 2-amino-4-cyanomethyl-6-dialkylamino-3,5-pyridinedicarbonitriles

Alkylation of the title pyridinedicarbonitriles with N-substituted chloroacetamides was found to give 5,6-diamino-8-dialkylamino-2,3-dihydro-2-oxo-1H-pyrrolo[2,3-c]2,7-naphthyridine-9-carbonitriles. The structure of obtained compounds was unambiguously confirmed by X-ray crystallographic study. The heterocyclization reaction proceeded regioselectively involving 3-CN group of the starting pyridines without participation of 5-CN. The reasons of the selectivity were discussed. An interaction of prepared naphthyridine derivatives with acetic acid anhydride and cyclohexanone yielded 2-dialkylamino-6,8,9,10-tetrahydro-5-methyl-9-oxopyrimido[4,5,6-ij]pyrrolo[2,3-c]2,7-naphthyridine-1-carbonitriles and 2-dialkylamino-4,5,6,8,9,10-hexahydro-9-oxospiro{pyrimido[4,5,6-ij]pyrrolo[2,3-c]2,7-naphthyridine-5,1′-cyclohexane}-1-carbonitriles, respectively. All fused 2,7-naphthyridines obtained were derivatives of novel heterocyclic systems.     

Investigation of the interaction of dimethyl sulfoxide with lipid membranes by small-angle neutron scattering

The influence of dimethyl sulfoxide (CH₃)₂SO (DMSO) on the structure of membranes of 1,2-dimiristoyl-sn-glycero-3-phosphatidylcholine (DMPC) in an excess of a water-DMSO solvent is investigated over a wide range of DMSO molar concentrations 0.0 ≤ X _DMSO ≤ 1.0 at temperatures T = 12.5 and 55°C. The dependences of the repeat distance d of multilamellar membranes and the thickness d _b of single vesicles on the molar concentration X _DMSO in the L _β’ gel and L _α liquid-crystalline phases are determined by small-angle neutron scattering. The intermembrane distance d _s is determined from the repeat distance d and the membrane thickness d _b. It is shown that an increase in the molar concentration X _DMSO leads to a considerable decrease in the intermembrane distance and that, at X _DMSO = 0.4, the neighboring membranes are virtually in steric contact with each other. The use of the deuterated phospholipid (DMSO-D6) and the contrast variation method makes it possible, for the first time, to determine the number of DMSO molecules strongly bound to the membrane.     

On block Gaussian sketching for the Kaczmarz method

Numerical Algorithms - The Kaczmarz algorithm is one of the most popular methods for solving large-scale over-determined linear systems due to its simplicity and computational efficiency. This...     

Boswellic Acids as Effective Antibacterial Antibiofilm Agents

Boswellic acids are biologically active pentacyclic terpenoid compounds derived from Boswellia sp. plants. Extracts containing these acids have a number of positive effects on human health, especially in the treatment of inflammation, arthritis, or asthma. With increasing resistance to common antibiotics, boswellic acid-containing extracts could serve as an alternative or work in synergy with commonly available preparations. This study aims to determine the effect of boswellic acids on suspension cells and biofilms of Staphylococcus epidermidis, Enterococcus faecalis, and Escherichia coli. The antimicrobial and antibiofilm effect found was compared with commonly available antibiotics to control these undesirable microorganisms. The synergistic effect of boswellic acids and common antibiotics on the growth of these microorganisms was also determined. All tested microorganisms showed a positive additive effect of antibiotics and boswellic acid extract. The most significant effect was found in Enterococcus faecalis ATCC 29212 in a combination of 0.2 × MIC80 erythromycin (0.2 mg/L) and 0.8 × MIC80 boswellic acid extract (16 mg/L).