Fatigue crack nucleation in metallic materials

The process of fatigue crack nucleation in metallic materials is reviewed placing emphasis in results derived for pure FCC metals with wavy slip behavior. The relationship between Persistent Slip Bands (PSB`s) and crack initiation will be examined for both single crystals and polycrystals, including the conditions for inter- and transgranular crack nucleation and their connection to type of loading, crystallography and slip geometry. The latter has been found to be an important parameter in the nucleation of intergranular cracks in polycrystals subjected to high strain fatigue, whereby primary slip bands with long slip lengths impinging on a grain boundary produce intergranular crack nucleation under the right conditions. Recent results related to intergranular crack nucleation in copper bicrystals and crack nucleation in Cu/Sapphire interfaces indicate that this mechanism controls crack nucleation in those simpler systems as well. Furthermore, it is found that under multiple slip conditions the crack nucleation location is controlled by the presence of local single slip conditions and long slip lengths for a particular Burgers vector that does not have to be in the primary slip system

Chemotherapy in patients with unresected pancreatic cancer in Australia: A population-based study of uptake and survival

1 Aim Palliative chemotherapy improves symptom control and prolongs survival in patients with unresectable pancreatic cancer, but there is a paucity of data describing its use and effectiveness in everyday practice. We explored patterns of chemotherapy use in patients with unresected pancreatic cancer in Australia and the impact of use on survival. 2 Methods We reviewed the medical records of residents of New South Wales or Queensland, Australia, diagnosed with unresectable pancreatic adenocarcinoma between July 2009 and June 2011. Associations between receipt of chemotherapy and sociodemographic, clinical and health service factors were evaluated using logistic regression. We used Cox proportional hazards models to analyze associations between chemotherapy use and survival. 3 Results Data were collected for 1173 eligible patients. Chemotherapy was received by 44% (n = 184/414) of patients with localized pancreatic cancer and 53% (n = 406/759) of patients with metastases. Chemotherapy receipt depended on clinical factors, such as performance status and comorbidity burden, and nonclinical factors, such as age, place of residence, multidisciplinary team review and the type of specialist first encountered. Consultation with an oncologist mitigated most of the sociodemographic and service‐related disparities in chemotherapy use. The receipt of chemotherapy was associated with prolonged survival in patients with inoperable pancreatic cancer, including after adjusting for common prognostic factors. 4 Conclusions These findings highlight the need to establish referral pathways to ensure that all patients have the opportunity to discuss treatment options with a medical oncologist. This is particularly relevant for health care systems covering areas with a geographically dispersed population

Highly Parallel Translation of DNA Sequences into Small Molecules

A large body of in vitro evolution work establishes the utility of biopolymer libraries comprising 1010 to 1015 distinct molecules for the discovery of nanomolar-affinity ligands to proteins.[1], [2], [3], [4], [5] Small-molecule libraries of comparable complexity will likely provide nanomolar-affinity small-molecule ligands.[6], [7] Unlike biopolymers, small molecules can offer the advantages of cell permeability, low immunogenicity, metabolic stability, rapid diffusion and inexpensive mass production. It is thought that such desirable in vivo behavior is correlated with the physical properties of small molecules, specifically a limited number of hydrogen bond donors and acceptors, a defined range of hydrophobicity, and most importantly, molecular weights less than 500 Daltons.[8] Creating a collection of 1010 to 1015 small molecules that meet these criteria requires the use of hundreds to thousands of diversity elements per step in a combinatorial synthesis of three to five steps. With this goal in mind, we have reported a set of mesofluidic devices that enable DNA-programmed combinatorial chemistry in a highly parallel 384-well plate format. Here, we demonstrate that these devices can translate DNA genes encoding 384 diversity elements per coding position into corresponding small-molecule gene products. This robust and efficient procedure yields small molecule-DNA conjugates suitable for in vitro evolution experiments

Structure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor

Albumin is the most abundant protein in blood where it has a pivotal role as a transporter of fatty acids and drugs. Like IgG, albumin has long serum half-life, protected from degradation by pH-dependent recycling mediated by interaction with the neonatal Fc receptor, FcRn. Although the FcRn interaction with IgG is well characterized at the atomic level, its interaction with albumin is not. Here we present structure-based modelling of the FcRn–albumin complex, supported by binding analysis of site-specific mutants, providing mechanistic evidence for the presence of pH-sensitive ionic networks at the interaction interface. These networks involve conserved histidines in both FcRn and albumin domain III. Histidines also contribute to intramolecular interactions that stabilize the otherwise flexible loops at both the interacting surfaces. Molecular details of the FcRn–albumin complex may guide the development of novel albumin variants with altered serum half-life as carriers of drugs

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

Peer reviewe

Measurement of the Inclusive Charm Cross Section at 4.03 GeV and 4.14 GeV

The cross section for charmed meson production at $\sqrt{s} = 4.03$ and 4.14 GeV has been measured with the Beijing Spectrometer. The measurement was made using 22.3 $pb^{-1}$ of $e^+e^-$ data collected at 4.03 GeV and 1.5 $pb^{-1}$ of $e^+e^-$ data collected at 4.14 GeV. Inclusive observed cross sections for the production of charged and neutral D mesons and momentum spectra are presented. Observed cross sections were radiatively corrected to obtain tree level cross sections. Measurements of the total hadronic cross section are obtained from the charmed meson cross section and an extrapolation of results from below the charm threshold.Comment: 11 pages, 13 figures. The top level tex file is paper.tex. It builds the paper from other tex files in this .tar and the .eps file

Burkitt lymphoma masquerading as cardiac tamponade

A 61 year old man presented with diffuse large B cell lymphoma of the skin of the back of the shoulder which was excised and treated with chemotherapy (CHOP regime) in 1998. He was in complete remission till he presented in 2002 with extranodal marginal zone lymphoma of the parotid gland for which he underwent superficial parotidectomy and radiotherapy. He continued in remission till 2006 when he presented with recurrent pericardial effusion and tamponade. At median sternotomy, pericardial effusion was drained, an anterior pericardiectomy was done and a left posterior pericardial window made, and an enlarged hard paraaortic lymph node excised. Histology, immunocytochemistry and chromosome analysis revealed Burkitt lymphoma. Patient underwent chemotherapy with CODOX-M regime and continues in remission. This report is unusual on account of the highly atypical presentation of Burkitt lymphoma as cardiac tamponade, only a few cases having been reported previously, the occurrence of three lymphomas of different pathological and genomic profiles in one patient over a period of eight years and the relatively slow rate of growth of an otherwise fulminant tumour with high tumour doubling time. A review of literature with special emphasis on chromosomal diagnosis, transformation of other lymphomas into Burkitt lymphoma and mediastinal and cardiac involvement with Burkitt lymphoma is presented

IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells

IL-27 signaling directly into T cells is needed for follicular T helper cell survival, germinal center formation, and the production of T cell–dependent high-affinity antibodies in mice

Quantum dot labelling of adenovirus allows for highly sensitive single cell flow and imaging cytometry

A quantum dot method for highly efficient labelling of single adenoviral particles is developed. The technique has no impact on viral fitness and allows the imaging and tracking of virus binding and internalisation events using a variety of techniques including imaging cytometry and confocal microscopy. The method is applied to characterise the tropism of different adenoviral vectors