Jack to Professor Silver, 17 July 1963

Personal correspondenc

John C. Stephens, Jr. to Professor Silver, 4 January 1963

Professional correspondenc

Selective Michael additions to alkylidenemalonates using thiourea-based bifunctional organocatalysts

Bifunctional thiourea catalysts have been found to be excellent promoters of the challenging Michael addition to alkylidenemalonates giving high yields of up to 99%. Substrate structure was important for enantiodiscrimination, with aryl alkylidenemalonate acceptors furnishing products with ee values of up to 73%

A Consumer Test of Canned Seasoned Salad Tomatoes

Consumer, Canned Tomatoes, Salad Tomatoes, Seasoned Tomatoes, Consumer/Household Economics, Food Consumption/Nutrition/Food Safety,

Genome-wide profiling of human cap-independent translation-enhancing elements.

We report an in vitro selection strategy to identify RNA sequences that mediate cap-independent initiation of translation. This method entails mRNA display of trillions of genomic fragments, selection for initiation of translation and high-throughput deep sequencing. We identified >12,000 translation-enhancing elements (TEEs) in the human genome, generated a high-resolution map of human TEE-bearing regions (TBRs), and validated the function of a subset of sequences in vitro and in cultured cells

Synthesis, antibacterial and anti-MRSA activity, in vivo toxicity and a structure-activity relationship study of a quinoline thiourea

We report the synthesis, antibacterial evaluation of a series of thiourea-containing compounds. 1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-(6-methoxyquinolin-4-yl)-((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)thiourea 5, was the most active against a range of Gram-positive and Gram-negative bacteria, and exhibited bacteriostatic activity against methicillin resistant Staphylococcus aureus (MRSA) comparable to that of the well-known antibacterial agent vancomycin. Quinoline thiourea 5 was subjected to a detailed structure–activity relationship study, with 5 and its derivatives evaluated for their bacteriostatic activity against both Gram-negative and Gram-positive bacteria. A number of structural features important for the overall activity of quinoline thiourea 5 have been identified. A selection of compounds, including 5, was also evaluated for their in vivo toxicity using the larvae of the Greater wax moth, Galleria mellonella. Compound 5, and a number of derivatives, were found to be non-toxic to the larvae of Galleria mellonella. A new class of antibiotic can result from the further development of this family of compounds

G-Protein-Coupled Receptors as Therapeutic Targets for Glioblastoma

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumour in adults. Treatments include surgical resection, radiotherapy, and chemotherapy. Despite this, the prognosis remains poor, with an impacted quality of life during treatment coupled with brain tumour recurrence; thus, new treatments are desperately needed. In this review, we focus on recent advances in G-protein-coupled receptor (GPCR) targets. To date, the most promising targets are the chemokine, cannabinoid, and dopamine receptors, but future work should further examine the melanocortin receptor-4 (MC4R), adhesion, lysophosphatidic acid (LPA) and smoothened (Smo) receptors to initiate new drug-screening strategies and targeted delivery of safe and effective GBM therapies

Characteristics of stable flows over Southern Greenland

The main characteristic features of stable atmospheric flows over a large mountain plateau are summarised and then compared with mesoscale and synoptic scale numerical simulation, meteorological analysis, satellite imagery, and surface observations for the cases of flows over Southern Greenland for four wind directions. The detailed features are identified using the concepts and scaling of stably stratified flow over large mountains with variations in surface roughness, elevation, and heating. For westerly and easterly winds detached jets form at the southern tip, where coastal jets converge, which propagate large distances across the ocean. Near coasts katabatic winds can combine with barrier jets and wake flows generated by synoptic winds. Note how the approach flow rises/falls over southern Greenland for easterly/westerly winds, leading in both cases to more cloud on the western side. Some conclusions are drawn about the large-scale influences of these flows; detached jets in the atmosphere; air-sea interaction; formation of low pressure systems. For accurate simulations of these flows, mesoscale models are necessary with resolutions of order of 20 km or less. © Birkhäuser Verlag, Basel, 2005

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: a prospective cohort study

Background: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). Methods: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. Results: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. Conclusions: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series