The protein human CC chemokine ligand 2 (CCL2, also known as monocyte chemoattractant protein 1 or MCP‐1) has been synthesized using a combination of solid phase peptide synthesis (SPPS) and native chemical ligation (NCL). The thioester‐peptide segment was synthesized using the sulfonamide safety‐catch linker and 9‐fluorenylmethoxycarbonyl (Fmoc) SPPS, and pseudoproline dipeptides were used to facilitate the synthesis of both CCL2 fragments. After assembly of the full‐length peptide chain by NCL, a glutathione redox buffer was used to fold and oxidize the CCL2 protein. Synthetic human CCL2 binds to and activates the CCR2 receptor on THP‐1 cells, as expected. CCL2 was crystallized and the structure was determined by X‐ray diffraction at 1.9‐Å resolution. The structure of the synthetic protein is very similar to that of a previously reported structure of recombinant human CCL2, although the crystal form is different. The functional CCL2 dimer for the crystal structure reported here is formed around a crystallographic twofold axis. The dimer interface involves residues Val9‐Thr10‐Cys11, which form an intersubunit antiparallel β‐sheet. Comparison of the CCL2 dimers in different crystal forms indicates a significant flexibility of the quaternary structure. To our knowledge, this is one of the first crystal structures of a protein prepared using the sulfonamide safety‐catch linker and NCL. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 350–359, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Overall, a sizeable majority of adolescent and adult long-term survivors of childhood cancer in Canada appear to have adapted well.

BackgroundHigh levels of participation in cervical screening are reported in Canada from the 1970’s as a result of early uptake of the Pap smear and universal Medicare. Despite recommendations to the contrary, the programs have featured early age of initiation of screening and frequent screening intervals. Other countries have achieved successful outcomes without such features. We analyzed national data to better understand mortality and incidence trends, and their relationships to screening.MethodsThe Canadian Cancer Registry, National Cancer Incidence Reporting System, and the Canadian Vital Statistics Database were used to measure mortality and incidence rates. Cases and deaths from invasive cervical cancer were classified by 5 year age groups at diagnosis and death (15 to 19 years through to 80 to 84 years), year of diagnosis (1972 to 2006), and year of death (1932 to 2006). Probabilities of developing and dying from cervical cancer were calculated for age-specific mortality and incidence. The proportion of women reporting a timely Pap test was estimated for 1978 to 2006.ResultsCervical cancer mortality has declined steadily from a peak of 13.5 to 2.2 per 100,000 (83%,) between 1952 and 2006, and 71% between 1972 and 2006. Incidence of invasive cervical cancer has declined by 58% since 1972. These declines have occurred more among older age groups than younger. Invasive cervical cancer incidence and mortality is less in each successive birth cohort of women. Participation rates in screening are high especially in women under age 50.ConclusionsDespite increasing risk factors for cervical cancer, both incidence and mortality have declined over time, across age groups, and across birth cohorts. Earlier increasing mortality (1932 – 1950) was likely related to improved classification of cancers and the early subsequent reduction (1950 – 1970) to improved treatment. Recent improvements in incidence and mortality are likely due to high rates of screening. For women under age 30 years there are low rates of disease but lesser improvement related to screening.

Distance to treating center had no significant impact on waiting times for important diagnostic and treatment events, when adjusted for age at diagnosis, diagnosis, region, and first health care professional seen.