Do Loading Path and Specimen Thickness Affect the Brittle Compressive Failure of Ice?

Compressive experiments were performed on square (160 mm × 160 mm) prismatic specimens of columnar-grained, S2 freshwater ice, biaxially loaded across the columns at −10°C. The work focused on brittle behavior, achieved by deforming the specimens at an applied strain rate of 4.5 ± 1.2 × 10 3s 1 in the direction of shortening. The results show that the specimen thickness (25–150 mm) has no detectable effect on the terminal failure strength of the ice. Likewise, the strength of the ice when loaded under proportional loading, where the minor stress varies during the test, was similar to that when loaded under a constant minor stress, implying that terminal failure depends only on the stress state and not on the path taken

The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth.

The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2–2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids

Electrochemical [¹¹C]CO₂ to [¹¹C]CO conversion for PET imaging

Development of a novel electrochemical radiochemistry methodologyi.e.reduction of [11C]CO2to [11C]CO at room temperature and pressure using metal cyclam complexes.</p

Design, synthesis and initial characterisation of a radiolabelled [18F]pyrimidoindolone probe for detecting activated caspase-3/7

Evasion of apoptosis is one of the six initially proposed hallmarks of cancer, and as such, a method to detect apoptosis in a tumour would be of considerable interest in both clinical trials of new cancer therapeutics, as well as for routine patient management. Activation of caspase-3/7 is a key biomarker of cellular apoptosis. Herein we describe the design, synthesis and initial characterisation of the first pyrimidoindolone compound for detection of caspase-3/7 activation using positron emission tomography

Consistency in the observation of features used to classify duct carcinoma in situ (DCIS) of the breast

Aim—To determine interobserver and intra-observer agreement in the assessment of cytological grade and intraduct necrosis in pure duct carcinoma in situ (DCIS) of the breast. Methods—Sixty unselected cases with illustrated diagnostic criteria were circulated to 19 practising histopathologists. Results—Overall agreement was moderate for cytological grade in three categories: 71% agreement; weighted κ (κw), 0.36; intraduct necrosis in three categories (absent, present, extensive): 76% agreement; κw, 0.57; and the Van Nuys classification system: 73% agreement; κw, 0.48. Agreement was no better among observers participating in the National External Quality Assurance Programme. Intra-observer agreement for cytological assessment (69.6% agreement; κw, 0.52) and intraduct necrosis (68.3% agreement; κw, 0.48) was moderate, suggesting that individual variation rather than precision of criteria contributes to the lack of agreement. Conclusions—Moderate agreement on observations can be achieved by non-specialist pathologists, with better agreement on necrosis than cytological grade. There was evidence of consistent individual bias towards over or under scoring cytological grade, which could be corrected with adequate and prompt feedback. Key Words: classification • duct carcinoma in situ • breast • intraduct necrosi