Rapid analysis of charge variants of monoclonal antibodies with capillary zone electrophoresis in dynamically coated fused-silica capillary

A capillary zone electrophoresis (CZE) method was developed for the rapid analysis of charge heterogeneity of immunoglobulin G (IgG) monoclonal antibodies (mAbs). The separation was carried out in a short, dynamically coated fused-silica capillary. A number of separation parameters were investigated and optimized, including pH, concentration of the separation buffer (ε-amino caproic acid), concentration of the triethylenetetramine (TETA) dynamic coating, the capillary internal diameter and the field strength used for the separation. The effects of between-run flushing of the capillary and the data acquisition rate were also evaluated. Under the optimized conditions, a fast (<5 min), selective and reproducible separation of mAb charge variants was achieved under a very high electric field strength (1000 V/cm). This method also requires only a short conditioning of the capillary, with between-run conditioning completed within 2 min. The method was evaluated for specificity, sensitivity, linearity, accuracy and precision. The same separation conditions were applied to the rapid separation (2-5 min) of charge variants of multiple monoclonal antibodies with pI in the range of 7.0-9.5. Compared with other existing methods for charge variants analysis, this method has several advantages including a short run time, rapid capillary conditioning and simple sample preparation.     

DNA-capped nanoparticles designed for doxorubicin drug delivery

The anticancer drug, doxorubicin (DOX), was loaded onto DNA-capped gold nanoparticles (AuNP) designed for specific DOX intercalation. Drug binding was confirmed by monitoring DNA melting temperature, AuNP plasmon resonance maximum, and hydrodynamic radius increase, as a function of [DOX]/[DNA] ratio. The capacity for drug release to target DNA was confirmed.     

On invariants of modular categories beyond modular data

We study novel invariants of modular categories that are beyond the modular data, with an eye towards a simple set of complete invariants for modular categories. Our focus is on the W-matrix—the quantum invariant of a colored framed Whitehead link from the associated TQFT of a modular category. We prove that the W-matrix and the set of punctured S-matrices are strictly beyond the modular data $(S,T)$. Whether or not the triple $(S,T,W)$ constitutes a complete invariant of modular categories remains an open question.     

Pt(II) and Pt(IV) amido, aryloxide, and hydrocarbyl complexes: synthesis, characterization, and reaction with dihydrogen and substrates that possess C-H bonds

The Pt(II) amido and phenoxide complexes ((t)bpy)Pt(Me)(X), ((t)bpy)Pt(X)(2), and [((t)bpy)Pt(X)(py)][BAr'(4)] (X = NHPh, OPh; py = pyridine) have been synthesized and characterized. To test the feasibility of accessing Pt(IV) complexes by oxidizing their Pt(II) precursors, the previously reported ((t)bpy)Pt(R)(2) (R = Me and Ph) systems were oxidized with I(2) to yield ((t)bpy)Pt(R)(2)(I)(2). The analogous reaction with ((t)bpy)Pt(Me)(NHPh) and MeI yields the corresponding ((t)bpy)Pt(Me)(2)(NHPh)(I) complex. Reaction of ((t)bpy)Pt(Me)(NHPh) and phenylacetylene at 80 °C results in the formation of the Pt(II) phenylacetylide complex ((t)bpy)Pt(Me)(C≡CPh). Kinetic studies indicate that the reaction of ((t)bpy)Pt(Me)(NHPh) and phenylacetylene occurs via a pathway that involves [((t)bpy)Pt(Me)(NH(2)Ph)][TFA] as a catalyst. The reaction of H(2) with ((t)bpy)Pt(Me)(NHPh) ultimately produces aniline, methane, (t)bpy, and elemental Pt. For this reaction, mechanistic studies reveal that 1,2-addition of dihydrogen across the Pt-NHPh bond to initially produce ((t)bpy)Pt(Me)(H) and free aniline is catalyzed by elemental Pt. Heating the cationic complexes [((t)bpy)Pt(NHPh)(py)][BAr'(4)] and [((t)bpy)Pt(OPh)(py)][BAr'(4)] in C(6)D(6) does not result in the production of aniline and phenol, respectively. Attempted synthesis of a cationic system analogous to [((t)bpy)Pt(NHPh)(py)][BAr'(4)] with ligands that are more labile than pyridine (e.g., NC(5)F(5)) results in the formation of the dimer [((t)bpy)Pt(μ-NHPh)](2)[BAr'(4)](2). Solid-state X-ray diffraction studies of the complexes ((t)bpy)Pt(Me)(NHPh), [((t)bpy)Pt(NH(2)Ph)(2)][OTf](2), ((t)bpy)Pt(NHPh)(2), ((t)bpy)Pt(OPh)(2), ((t)bpy)Pt(Me)(2)(I)(2), and ((t)bpy)Pt(Ph)(2)(I)(2) are reported.     

Geodesics in Randers spaces of constant curvature

Geodesics in Randers spaces of constant curvature are classified.

     

Oropharyngeal pH Monitoring for the Detection of Liquid and Aerosolized Supraesophageal Gastric Reflux

The association between gastroesophageal reflux disease (GERD) and extraesophageal symptoms is poorly understood and difficult to document. pH monitoring in this group of patients has resulted in conflicting data due to lack of diagnostic sensitivity. Recently, a new sensitive pH device for detection of liquid and aerosolized droplets in the oropharynx (The Dx–pH Measurement System [Dx–pH]) has become available. Our hypothesis is that we will be able to improve our ability to identify and understand this group of patients with this device. The aim of this preliminary observation study was to compare the results of this new device to the standard esophageal and pharyngeal pH probes in a small group of patients with extraesophageal symptoms. Patients with suspected extraesophageal GER symptoms underwent traditional 24-hour esophago-pharyngeal pH monitoring (24pH) simultaneous with Dx–pH monitoring in the oropharynx. Tracings were reviewed for comparison and correlation between the two probes, with an event in the Dx–pH Probe being defined as a rapid drop >3 standard deviation from baseline. Fifteen patients (10 females, 5 males) with mean age of 57.5 years (range, 25–75) were studied. The predominant chief complaint included 12/15 chronic cough, 2/15 asthma; and 1/15 throat clearing. All Dx–pH events were preceded and associated with distal esophageal pH drops in a progressive ante grade manner. Ten patients had 1–13 abnormal oropharyngeal pH events as measured by Dx–pH monitoring with a total of 48 events. The median pH of reflux events had a statistically significant increase from 3.1 at the distal esophageal probe to 5.2 at the pharynx and 5.6 at the oropharynx, the latter being 80% higher than the distal esophageal probe (P < 0.001). The percentage of acid events decreased in a cephalad manner from 66.7% at distal esophagus to 25% at the pharynx and only 6.25% at the oropharyngeal Dx–pH Probe, with the remaining events being weakly acidic. Dx–pH Probe is a new sensitive oropharyngeal pH device whose values correlate well with the gold-standard 24-hour pH device, and appears to accurately detect pH events that begin at the distal esophagus and travel upward to the oropharynx. This device suggests that supraesophageal events manifest themselves as rapid pH drops (>10%), which are likely not to be identified using the standard criteria of pH <4 due to the gradient of increasing pH from the lower esophagus to the oropharynx.