Enantioselective Synthesis of a Hydroxymethyl-cis-1,3-cyclopentenediol Building Block

A brief, enantioselective synthesis of a hydroxymethyl-cis-1,3-cyclopentenediol building block is presented. This scaffold allows access to the cis-1,3-cyclopentanediol fragments found in a variety of biologically active natural and non-natural products. This rapid and efficient synthesis is highlighted by the utilization of the palladium-catalyzed enantioselective allylic alkylation of dioxanone substrates to prepare tertiary alcohols

Confronting Standard Models of Proto--Planetary Disks With New Mid--Infrared Sizes from the Keck Interferometer

We present near and mid-infrared interferometric observations made with the Keck Interferometer Nuller and near-contemporaneous spectro-photometry from the IRTF of 11 well known young stellar objects, several observed for the first time in these spectral and spatial resolution regimes. With AU-level spatial resolution, we first establish characteristic sizes of the infrared emission using a simple geometrical model consisting of a hot inner rim and mid-infrared disk emission. We find a high degree of correlation between the stellar luminosity and the mid-infrared disk sizes after using near-infrared data to remove the contribution from the inner rim. We then use a semi-analytical physical model to also find that the very widely used "star + inner dust rim + flared disk" class of models strongly fails to reproduce the SED and spatially-resolved mid-infrared data simultaneously; specifically a more compact source of mid-infrared emission is required than results from the standard flared disk model. We explore the viability of a modification to the model whereby a second dust rim containing smaller dust grains is added, and find that the two-rim model leads to significantly improved fits in most cases. This complexity is largely missed when carrying out SED modelling alone, although detailed silicate feature fitting by McClure et al. 2013 recently came to a similar conclusion. As has been suggested recently by Menu et al. 2015, the difficulty in predicting mid-infrared sizes from the SED alone might hint at "transition disk"-like gaps in the inner AU; however, the relatively high correlation found in our mid-infrared disk size vs. stellar luminosity relation favors layered disk morphologies and points to missing disk model ingredients instead

Unified Enantioselective, Convergent Synthetic Approach Toward the Furanobutenolide-Derived Polycyclic Norcembranoid Diterpenes: Synthesis of a Series of Ineleganoloids by Oxidation State Manipulation of the Carbocyclic Core

Late-stage synthetic efforts to advance the enatio- and diastereoselectively constructed [6,7,5,5]-fused tetracyclic scaffold toward the polycyclic norditerpenoid ineleganolide are disclosed. The described investigations focus on oxidation-state manipulation around the central cycloheptane ring. Computational evaluation of ground-state energies of dihydroineleganolide is used to rationalize empirical observations and provide insight for further synthetic development, enhancing the understanding of the conformational constraints of these compact polycyclic structures. Advanced synthetic manipulations generated a series of natural product-like compounds termed the ineleganoloids

Enantioselective, convergent synthesis of the ineleganolide core by a tandem annulation cascade

An enantioselective and diastereoselective approach toward the synthesis of the polycyclic norditerpenoid ineleganolide is disclosed. A palladium-catalyzed enantioselective allylic alkylation is employed to stereoselectively construct the requisite chiral tertiary ether and facilitate the synthesis of a 1,3-cis-cyclopentenediol building block. Careful substrate design enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold by a diastereoselective cyclopropanation–Cope rearrangement cascade under unusually mild conditions. Computational evaluation of ground state energies of late-stage synthetic intermediates was used to guide synthetic development and aid in the investigation of the conformational rigidity of these highly constrained and compact polycyclic structures. This work represents the first successful synthesis of the core structure of any member of the furanobutenolide-derived polycyclic norcembranoid diterpene family of natural products. Advanced synthetic manipulations generated a series of natural product-like compounds that were shown to possess selective secretory antagonism of either interleukin-5 or interleukin-17. This bioactivity stands in contrast to the known antileukemic activity of ineleganolide and suggests the norcembranoid natural product core may serve as a useful scaffold for the development of diverse therapeutics

Absence of Acanthocytosis in Huntington’s Disease-like 2: A Prospective Comparison with Huntington’s Disease

Background: Huntington’s Disease-like 2 (HDL2) is classified as a neuroacanthocytosis; however, this remains unverified. We aim to determine if acanthocytes are present in HDL2 and whether acanthocytes can differentiate HDL2 from Huntington’s disease (HD). Methods: We prospectively compared 13 HD and 12 HDL2 cases against 21 unaffected controls in Johannesburg. Blood smears were prepared using international standards and reviewed by at least two blinded reviewers. An acanthocytosis rate of greater than 1.2% in the dry smear or greater than 3.7% in the wet smear was designated a priori as the threshold for clinical significance based on previously established standards. Flow cytometry was performed on all but four of the cases. Red cell membrane protein analysis was performed on all participants. Results: There were 12 HDL2, 13 HD, and 21 controls enrolled. None of the HD or HDL2 participants had defined acanthocytosis or other morphological abnormalities. None of the HD or HDL2 cases had evidence of an abnormal band 3. Discussion: Acanthocytosis was not identified in either HDL2 or HD in our patient population. Our results, based on the first prospective study of acanthocytes in HDL2 or HD, suggest that screening for acanthocytes will not help establish the diagnosis of HD or HDL2, nor differentiate between the two disorders and raises the question if HDL2 should be placed within the neuroacanthocytosis syndromes

A Mosquito Pick-and-Place System for PfSPZ-based Malaria Vaccine Production

The treatment of malaria is a global health challenge that stands to benefit from the widespread introduction of a vaccine for the disease. A method has been developed to create a live organism vaccine using the sporozoites (SPZ) of the parasite Plasmodium falciparum (Pf), which are concentrated in the salivary glands of infected mosquitoes. Current manual dissection methods to obtain these PfSPZ are not optimally efficient for large-scale vaccine production. We propose an improved dissection procedure and a mechanical fixture that increases the rate of mosquito dissection and helps to deskill this stage of the production process. We further demonstrate the automation of a key step in this production process, the picking and placing of mosquitoes from a staging apparatus into a dissection assembly. This unit test of a robotic mosquito pick-and-place system is performed using a custom-designed micro-gripper attached to a four degree of freedom (4-DOF) robot under the guidance of a computer vision system. Mosquitoes are autonomously grasped and pulled to a pair of notched dissection blades to remove the head of the mosquito, allowing access to the salivary glands. Placement into these blades is adapted based on output from computer vision to accommodate for the unique anatomy and orientation of each grasped mosquito. In this pilot test of the system on 50 mosquitoes, we demonstrate a 100% grasping accuracy and a 90% accuracy in placing the mosquito with its neck within the blade notches such that the head can be removed. This is a promising result for this difficult and non-standard pick-and-place task.Comment: 12 pages, 11 figures, Manuscript submitted for Special Issue of IEEE CASE 2019 for IEEE T-AS