Loss of Corneal Nerves and Corneal Haze in Patients with Fuchs' Endothelial Corneal Dystrophy with the Transcription Factor 4 Gene Trinucleotide Repeat Expansion.

Objective: Seventy percent of Fuchs' endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the transcription factor 4 gene (). The objective of this study was to characterize the corneal subbasal nerve plexus and corneal haze in patients with FECD with (RE+) and without the trinucleotide repeat expansion (RE-) and to assess the correlation of these parameters with disease severity.

Design: Cross-sectional, single-center study.

Predictors of Early Onset Glaucoma.

Purpose/relevance: To determine the influence of hypertension (HTN), type 2 diabetes (DM2), migraine, and obstructive sleep apnea (OSA) on the onset of primary open-angle glaucoma (POAG) to enhance predictive accuracy.

Methods: In this cross-sectional study, data for 389 eligible patients with POAG were collected through medical records review and phone surveys. All data were assessed collectively using stepwise multiple regression analysis to determine the relative contribution to age at POAG diagnosis.

PCA062, a P-cadherin Targeting Antibody-Drug Conjugate, Displays Potent Antitumor Activity Against P-cadherin-expressing Malignancies.

The cell surface glycoprotein P-cadherin is highly expressed in a number of malignancies, including those arising in the epithelium of the bladder, breast, esophagus, lung, and upper aerodigestive system. PCA062 is a P-cadherin specific antibody-drug conjugate that utilizes the clinically validated SMCC-DM1 linker payload to mediate potent cytotoxicity in cell lines expressing high levels of P-cadherin , while displaying no specific activity in P-cadherin-negative cell lines. High cell surface P-cadherin is necessary, but not sufficient, to mediate PCA062 cytotoxicity.

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms.

SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression.

Distinct Transcriptional Programming Drive Response to MAPK Inhibition in -Mutant Melanoma Patient-Derived Xenografts.

Inhibitors targeting and its downstream kinase MEK produce robust response in patients with advanced -mutant melanoma. However, the duration and depth of response vary significantly between patients; therefore, predicting response remains a significant challenge. Here, we utilized the Novartis collection of patient-derived xenografts to characterize transcriptional alterations elicited by and MEK inhibitors , in an effort to identify mechanisms governing differential response to MAPK inhibition.

A CMOS millimeter-wave transceiver embedded in a semi-confocal Fabry-Perot cavity for molecular spectroscopy.

The extension of radio frequency complementary metal oxide semiconductor (CMOS) circuitry into millimeter wavelengths promises the extension of spectroscopic techniques in compact, power efficient systems. We are now beginning to use CMOS millimeter devices for low-mass, low-power instrumentation capable of remote or in situ detection of gas composition during space missions. We have chosen to develop a Flygare-Balle type spectrometer, with a semi-confocal Fabry-Perot cavity to amplify the pump power of a mm-wavelength CMOS transmitter that is directly coupled to the planar mirror of the cavity.

Chemical crosslinking and mass spectrometric identification of interaction sites within soluble aggregate of protein therapeutics.

Protein aggregation presents a major challenge to bioengineering. In the present study, chemical crosslinking and mass spectrometry are employed to probe the interaction amongst soluble oligomer formed by Fc molecule of monoclonal antibody. Aggregation was induced by thermal stress at 42°C for 6h under physiological pH.

Neutral loss of isocyanic acid in peptide CID spectra: a novel diagnostic marker for mass spectrometric identification of protein citrullination.

Protein citrullination is emerging as an important signaling mechanism that modulates a variety of biological processes. This protein modification constitutes only a 1 Da mass shift, and can be readily confused with other common protein modifications that yield an identical mass shift. In an attempt to develop a robust methodology for detection of protein citrullination sites, we analyzed synthetic citrulline-containing peptides by electrospray ionization tandem mass spectrometry.