In situ investigation of phosphonate retarder interaction in oil well cements at elevated temperature and pressure conditions.

The effect of a high-performance retarding additive in oil well cements was investigated under elevated temperature (165°C) and pressure (1000 psi) conditions via in situ synchrotron-based X-ray diffraction (XRD) and quasielastic neutron scattering (QENS) techniques. Under these temperature and pressure conditions, crystalline calcium silicate hydrates (C-S-H) are formed through the cement hydration process. From in situ XRD experiments, the retardation effect was observed by a change in the rate of the appearance of 11 Å tobermorites as well as a change in the rate of the α-CSH generation and depletion.

Immediate Internal Fixation of Open Ankle Fractures: Report of Thirty-eight Cases Treated with a Standard Protocol.

We reviewed thirty-eight cases of open ankle fractures that had been treated with a standard protocol: alignment and splinting of the fracture at the scene of injury if possible, antibiotics administered in the emergency room and continued for forty-eight hours, admission of the patient to the operating room as quickly as possible, copious irrigation and thorough debridement of the wound, immediate rigid anatomical internal fixation, and delayed primary closure at five days. All of the fractures united, but three patients required subsequent ankle fusion because of cartilage damage noted at the initial operation. Of the thirty-five ankles with complete follow-up, the functional result was excellent in twenty-six and fair or poor in nine.

A chemoselective strategy for late-stage functionalization of complex small molecules with polypeptides and proteins.

Conjugates between proteins and small molecules enable access to a vast chemical space that is not achievable with either type of molecule alone; however, the paucity of specific reactions capable of functionalizing proteins and natural products presents a formidable challenge for preparing conjugates. Here we report a strategy for conjugating electron-rich (hetero)arenes to polypeptides and proteins. Our bioconjugation technique exploits the electrophilic reactivity of an oxidized selenocysteine residue in polypeptides and proteins, and the electron-rich character of certain small molecules to provide bioconjugates in excellent yields under mild conditions.

Antibody-Bactericidal Macrocyclic Peptide Conjugates To Target Gram-Negative Bacteria.

To combat antimicrobial infections, new active molecules are needed. Antimicrobial peptides, ever abundant in nature, are a fertile starting point to develop new antimicrobial agents but suffer from low stability, low specificity, and off-target toxicity. These drawbacks have limited their development.

Discovery of a potent respiratory syncytial virus RNA polymerase inhibitor.

Targeting viral polymerases has been a proven and attractive strategy for antiviral drug discovery. Herein we describe our effort in improving the antiviral activity and physical properties of a series of benzothienoazepine compounds as respiratory syncytial virus (RSV) RNA polymerase inhibitors. The antiviral activity and spectrum of this class was significantly improved by exploring the amino substitution of the pyridine ring, resulting in the discovery of the most potent RSV A polymerase inhibitors reported to date.

Novel bacterial NAD+-dependent DNA ligase inhibitors with broad-spectrum activity and antibacterial efficacy in vivo.

DNA ligases are indispensable enzymes playing a critical role in DNA replication, recombination, and repair in all living organisms. Bacterial NAD+-dependent DNA ligase (LigA) was evaluated for its potential as a broad-spectrum antibacterial target. A novel class of substituted adenosine analogs was discovered by target-based high-throughput screening (HTS), and these compounds were optimized to render them more effective and selective inhibitors of LigA.

Different modes of action of naphthyridones in gram-positive and gram-negative bacteria.

Naphthyridones that were recently described as a class of translation inhibitors in gram-positive bacteria mediate their mode of action via GyrA in Haemophilus influenzae and Escherichia coli. These are the first examples of compounds in which modes of action in different bacterial pathogens are mediated through widely different targets.

Functional outcomes following displaced talar neck fractures.

Objectives: To determine the outcome of displaced talar neck fractures at long-term follow-up in terms of functional outcome and secondary reconstructive surgery.

Design: Retrospective cohort study.

Setting: Academic level 1 trauma center.