Probing the Origin of Affinity in the GM1-Cholera Toxin Complex through Site-Selective Editing with Fluorine.

Carbohydrates regulate an inimitable spectrum of biological functions, yet successfully leveraging this therapeutic avenue continues to be frustrated by low affinities with glycan-specific proteins. A conspicuous exception is the interaction of monosialotetrahexosylganglioside (GM1) with the carbohydrate-recognition domain of cholera toxin from : this is one of the strongest protein-carbohydrate interactions known. To establish the importance of a long-discussed key hydrogen bond between C2 of the terminal galactose of GM1 and the B subunit pentamer of cholera toxin (CTB), the total synthesis of a selectively fluorinated GM1 epitope was conducted in 19 steps.

A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C.

Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as a vaccine lead against serogroups C and/or B. Emulating the importance of fluorine in drug discovery, this molecular editing approach serves a multitude of purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation of the disialoside with two carrier proteins (CRM197 and PorA) enabled a semisynthetic vaccine to be generated; this was then investigated in six groups of six mice.

-Selective dearomatization of phenols by I(i)/I(iii) catalysis-based fluorination.

The regio- and enantio-selective dearomatization of phenols has been achieved by I(i)/I(iii) catalysis enabled fluorination. The process is highly -selective, guiding the fluoride nucleophile to the distal C4 position of the substrate to generate fluorinated cyclohexadienones in an operationally simple manner. Extensive optimization has revealed key parameters that orchestrate enantioselectivity in this historically challenging transformation.

Skeletal Ring Contractions via I(I)/I(III) Catalysis: Stereoselective Synthesis of -α,α-Difluorocyclopropanes.

The clinical success of α,α-difluorocyclopropanes, combined with limitations in the existing synthesis portfolio, inspired the development of an operationally simple, organocatalysis-based strategy to access -configured derivatives with high levels of stereoselectivity (up to >20:1 :). Leveraging an I(I)/I(III)-catalysis platform in the presence of an inexpensive HF source, it has been possible to exploit disubstituted bicyclobutanes (BCBs) as masked cyclobutene equivalents for this purpose. generation of this strained alkene, enabled by Brønsted acid activation, facilitates an unprecedented 4 → 3 fluorinative ring contraction, to furnish -α,α-difluorinated cyclopropanes in a highly stereoselective manner (up to 88% yield).

Automated guidance algorithms for a space station-based crew escape vehicle.

An escape vehicle was designed to provide an emergency evacuation for crew members living on a space station. For maximum escape capability, the escape vehicle needs to have the ability to safely evacuate a station in a contingency scenario such as an uncontrolled (e.g.

Influence of selection criteria on mutation detection in patients with hereditary nonpolyposis colorectal cancer.

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is linked genetically to mutations in DNA mismatch repair (MMR) genes. Because a deficiency in MMR does not predict a specific phenotype, the original selection criteria may be too restrictive in identifying additional families. The current study was performed to determine whether a relaxation of the Amsterdam criteria (AC) could be applied to identify more families associated with DNA MMR.

Gd-DOTA as a gastrointestinal contrast agent for gastric emptying measurements with MRI.

Current MR meal markers may interfere with gastric motility and secretion restricting the use of MRI in the measurement of gastric physiology. We therefore evaluated Gd-DOTA as a liquid phase marker, in vitro by determining dissociation, and adherence to the solids, and in vivo by simultaneous MRI (0.35 T scanner, multiple T1-weighted sections of the upper abdomen) and double indicator (perfusion marker PEG 4000, meal marker 99mTc-DTPA) measurements of emptying and secretion, following ingestion of 500 ml 10% glucose.

Heart and lung grafts harvested en bloc: operative technique, utilization, and results.

Combined heart and lung transplantation has been shown to provide successful therapy for patients with end-stage heart and lung disease. The improved success of lung transplantation has resulted in increasing number of potential recipients and longer waiting times. Maximal utilization of all three thoracic organs is no longer a casual goal but of utmost necessity.

Antibody labeling with copper-67 using the bifunctional macrocycle 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid.

The high kinetic stability of the Cu2+ complex of the chelator 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl]benzoic acid was demonstrated at physiological pH as well as under acidic conditions. The chelating agent was conjugated to AB35, a monoclonal antibody directed against CEA, without a significant loss of immunoreactivity. The conjugate could, under optimal labeling conditions, be labeled with 67Cu in acetate buffer with a full occupancy of ligands within 20 min.

Oversizing of donor hearts: beneficial or detrimental?

To determine the effects of donor/recipient weight mismatch on allograft function and survival after orthotopic heart transplantation, we retrospectively compared the clinical and the hemodynamic characteristics of recipients weighing more than their donor ("undersized") with those of recipients weighing less than their donor ("oversized"). The median follow-up period was 24 months (range, 0 to 67 months). In 88 patients (59%) donor weight was 1% to 46% less than recipient weight (13.

Androgens inhibit proliferation of human peripheral blood lymphocytes in vitro.

The effect of sex hormones on human lymphocytes was examined in vitro on cell cultures of human peripheral blood mononuclear cells (HPBM). Cells were stimulated using T- and B-cell mitogens, and hormones in physiological (nM) or pharmacological (microM) concentrations were added. Proliferation was determined by measuring the incorporation of tritiated thymidine.