Cyclic and Lasso Peptides: Sequence Determination,Topology Analysis,and Rotaxane Formation

A broadly applicable chemical cleavage methodology to facilitate MS/MS sequencing was developed for macrocyclic and lasso peptides, which hold promise as exciting new therapeutics. Existing methods such as Edman degradation, CNBr cleavage, and enzymatic digestion are either limited in scope or completely fail in cleavage of constrained nonribosomal peptides. Importantly, the new method was utilized for synthesizing a unique peptide‐based rotaxane (both cyclic and threaded) from the lasso peptide, benenodin‐1 ΔC5.     

Docking Strategy To Construct Thermostable,Single‐Crystalline,Hydrogen‐Bonded Organic Framework with High Surface Area

Enhancing thermal and chemical durability and increasing surface area are two main directions for the construction and improvement of the performance of porous hydrogen‐bonded organic frameworks (HOFs). Herein, a hexaazatriphenylene (HAT) derivative that possesses six carboxyaryl groups serves as a suitable building block for the systematic construction of thermally and chemically durable HOFs with high surface area through shape‐fitted docking between the HAT cores and interpenetrated three‐dimensional network. A HAT derivative with carboxybiphenyl groups forms a stable single‐crystalline porous HOF that displays protic solvent durability, even in concentrated HCl, heat resistance up to 305 °C, and a high Brunauer–Emmett–Teller surface area [SA_(BET)] of 1288 m² g^?1. A single crystal of this HOF displays anisotropic fluorescence, which suggests that it would be applicable to polarized emitters based on robust functional porous materials.     

Surface modification. I. Polyacrolein microspheres covalently bonded onto polyethylene

The synthesis and characterization of novel surfaces composed of polyacrolein microspheres covalently bonded onto polyethylene films are described. These surfaces were prepared through a sequence of reactions carried out onto polyethylene films in order to form primary amine groups at the w position. Polyacrolein microspheres in water were then covalently bonded to these modified polyethylene surfaces. The binding between the microspheres and the modified surfaces is due to the interaction between the aldehyde groups of the microspheres and the amine groups of the modified surfaces to form the polyvalent Schiff base bonds. Fourier transform-infrared/attenuated total reflection, electron spectroscopy for chemical analysis, contact angle measurements, and scanning electron microscopy have been used for the characterization of the modified polyethylene surfaces.     

Microsphere based continuous-flow immunoassay in a microfluidic device for determination of clinically relevant insulin levels

This paper describes a miniaturized microsphere-based immunoassay integrated into a microfluidic device for rapid quantitation of insulin. Analysis of bionic pancreas studies have revealed that the rates of absorption of insulin analogs vary from patient to patient, and even within patients on different occasions. Thus development of an approach to monitor insulin continuously allows the pharmacokinetic characteristics of insulin analogs to be determined in real-time. The authors have developed a microsphere-based continuous flow assay in a microfluidic chip that allows for the detection of insulin within seconds with high sensitivity and specificity. The method was applied to near real-time monitoring of clinical samples. Calibration plot were established for different insulin analogs such as insulin aspart (Novolog), insulin lispro (Humalog), and regular human insulin (RHI) and the insulin detection limit was 0.26 ng.mL^?1 (44 pM). This sensitivity allows to detect the fasting insulin levels of T1D patients, which are reported in the range of 50–180 pM (0.3–1 ng.mL^?1), after treatment with subcutaneous insulin administration. This fast approach was also applied to sera collected in intervals from T1D patients after a bolus of insulin aspart delivery. The insulin profile obtained by this method is similar to the basal and peak insulin levels as determined using the standard non-continuous ELISA reference method. In our perception, this assay will improve healthcare by personalizing diagnostics for better clinical outcome and provide real-time feedback on sensing and actuation.

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Graphical abstract Schematic illustration of the microfluidic microsphere based Microfluidic Lab-On-Chip device for near real-time insulin monitoring.

     

Introduction of metastatic heterogeneity by short-term in vivo passage of a cloned transformed cell line

An experimental system for the study of metastasis has been developed using an epithelioid cell line of hepatic origin which had previously been chemically transformed in vitro. These metastatic cells were studied in the syngeneic rat strain. The cloned parent cell line metastasizes only to the lungs following intravenous, subcutaneous, or intraperitoneal injection. The metastatic phenotype is stable during in vitro passage, and subclones from the parent clone have a metastatic capacity statistically similar to that of the parent clone. Following ascites passage of the parent cell line, the cell population obtained exhibits the same metastatic ability as the parent clone. However, subclones obtained from the ascites-passaged population exhibit metastatic heterogeneity. This heterogeneity is introduced by the host passage and not by in vitro culture or subcloning. In the case of the two metastatic variants examined, the difference in the metastatic phenotype is found not to be due to differences in arrest or trapping of the cells but appears to be related to long-term survival and proliferation of the tumor cells following their arrest in the lungs. Morphologically the variants are very similar, and growth of the metastatic foci provokes a vigorous inflammatory response by the host.     

Inaccessible States in Time-Dependent Reaction Diffusion

Using asymptotic methods we show that the long-time dynamic behavior in certain systems of nonlinear parabolic differential equations is described by a time-dependent, spatially inhomogeneous nonlinear evolution equation. For problems with multiple stable states, the solution develops sharp fronts separating slowly varying regions. By studying the basins of attraction of Abel's nonlinear differential equation, we demonstrate that the presence of explicit time dependence in the asymptotic evolution equation creates “forbidden regions” where the existence of interfaces is excluded. Consequently, certain configurations of stable states in the nonlinear system become inaccessible and cannot be achieved from any set of real initial conditions.     

The Length of Primitive BCH Codes with Minimal Covering Radius

It is proved that the covering radius of a primitive binary BCH code of length q-1 and designed distance 2t+1, where is exactly 2t-1 (the minimum value possible). The bound for q is significantly lower than the one obtained by O. Moreno and C. J. Moreno [9].     

Auxiliary problem principle and decomposition of optimization problems

The auxiliary problem principle allows one to find the solution of a problem (minimization problem, saddle-point problem, etc.) by solving a sequence of auxiliary problems. There is a wide range of possible choices for these problems, so that one can give special features to them in order to make them easier to solve. We introduced this principle in Ref. 1 and showed its relevance to decomposing a problem into subproblems and to coordinating the subproblems. Here, we derive several basic or abstract algorithms, already given in Ref. 1, and we study their convergence properties in the framework of i infinite-dimensional convex programming.     

Linear Codes and Their Coordinate Ordering

A necessary and sufficientcondition for a q-ary code to satisfy the two-waychain condition (TCC) is found. A known construction of q-arycodes is shown to yield codes satisfying the TCC. Some q-arycodes of dimension k 6 meeting the Griesmerbound are proved to satisfy the TCC.