Exact edge singularities and dynamical correlations in spin-1/2 chains

Exact formulas for the singularities of the dynamical structure factor, Szz(q,omega), of the S=1/2 xxz spin chain at all q and any anisotropy and magnetic field in the critical regime are derived, expressing the exponents in terms of the phase shifts which are known exactly from the Bethe ansatz solution. We also study the long-time asymptotics of the self-correlation function 0|Sjz(t)Sjz(0)|0. Utilizing these results to supplement very accurate time-dependent density matrix renormalization group, for short to moderate times, we calculate Szz(q,omega) to very high precision.     

Rational design of thioamide peptides as selective inhibitors of cysteine protease cathepsin L

Aberrant levels of cathepsin L (Cts L), a ubiquitously expressed endosomal cysteine protease, have been implicated in many diseases such as cancer and diabetes. Significantly, Cts L has been identified as a potential target for the treatment of COVID-19 due to its recently unveiled critical role in SARS-CoV-2 entry into the host cells. However, there are currently no clinically approved specific inhibitors of Cts L, as it is often challenging to obtain specificity against the many highly homologous cathepsin family cysteine proteases. Peptide-based agents are often promising protease inhibitors as they offer high selectivity and potency, but unfortunately are subject to degradation in vivo. Thioamide substitution, a single-atom O-to-S modification in the peptide backbone, has been shown to improve the proteolytic stability of peptides addressing this issue. Utilizing this approach, we demonstrate herein that good peptidyl substrates can be converted into sub-micromolar inhibitors of Cts L by a single thioamide substitution in the peptide backbone. We have designed and scanned several thioamide stabilized peptide scaffolds, in which one peptide, R^S_1A, was stabilized against proteolysis by all five cathepsins (Cts L, Cts V, Cts K, Cts S, and Cts B) while inhibiting Cts L with >25-fold specificity against the other cathepsins. We further showed that this stabilized R^S_1A peptide could inhibit Cts L in human liver carcinoma lysates (IC₅₀ = 19 μM). Our study demonstrates that one can rationally design a stabilized, specific peptidyl protease inhibitor by strategic placement of a thioamide and reaffirms the place of this single-atom modification in the toolbox of peptide-based rational drug design.

Information on the effects of sidechain and backbone modification on the activity of cathepsin (Cts) L, V, K, S, and B was used to design a thioamide peptide that is inert to all Cts and selectively inhibits Cts L.     

Developments in the synthesis of maleated polyolefins by reactive extrusion

The maleation of conventional and metallocene linear low density polyethylenes by reactive extrusion has been explored with a view to defining the conditions necessary for a robust process that provides both high grafting efficiencies (>80%) and minimal degradation or cross-linking. The dependence of grafting efficiency on various operating parameters (maleic anhydride level, maleic anhydride:initiator ratio, throughput rate, direction of screw rotation, temperature) has been established. Literature methods for characterization of the grafted product based on FTIR or ¹H NMR analysis have been critically examined with respect to their ability to distinguish between single unit and oligomeric maleic anhydride grafts and found to yield ambiguous results.     

Preparation and characterization of iodinated poly(vinyl alcohol) microfibril

Iodination of poly(vinyl alcohol) (PVA) microfibril, which was obtained from saponification of poly(vinyl pivalate), was conducted before and after zone drawing at various conditions. The resulting PVA microfibrils were characterized by differential scanning calorimeter and scanning electron microscopy. Surface morphologies of these PVA microfibrils showed some differences between PVA microfibril iodinated after and before drawing. Crude shapes of PVA microfibrils iodinated after drawing indicated that iodine decreased the structural regularity severely. On the other hand, PVA microfibrils iodinated before drawing showed relatively ordered surfaces. This was ascribed to the enhanced molecular ordering of PVA microfibrils due on zone drawing. Iodinated PVA microfibrils showed a decrease in crystal melting temperature of about 100°C compared to the untreated sample. PVA microfibrils drawn after iodination showed relatively higher crystal melting temperature than those of microfibrils iodinated after drawing. These results were considered as the proofs of the changes in crystalline lattice of the PVA microfibrils. Effects, of drawing temperature on sublimation of iodine were also evaluated.     

Characterization of pyrene end-labeled poly(ethylene glycol) by high resolution MALDI time-of-flight mass spectrometry

We report the characterization of a sample of poly(ethylene glycol) (PEG, M _n = 3841, M _w/M _n = 1.01), and its derivative end-labeled with pyrenebutyrate groups, using high resolution MALDI time-of-flight mass spectrometry. A matrix of 2-(4-hydroxyphenyl-azo)benzoic acid containing a trace of either sodium chloride or potassium chloride was employed for laser desorption. Peaks due to the sodium or potassium cationized polymers were obtained, equally spaced at 44 mass units apart. For the pyrenebutyrate diester, the analysis shows that 80 ± 2% of the chains were doubly labeled, with the ramaining chains containing only a single pyrene group. Molecular weight determinations for both sets of samples were entirely consistent with size-exclusion chromatography measurements, but were obtained with greater accuracy and less ambiguity about the influence of the end groups on the hydrodynamic radius of the polymer.