Computational Study of the Structure and Thermodynamic Properties of Ammonium Chloride Clusters Using a Parallel J-Walking Approach

The thermodynamic and structural properties of (NH$_4$Cl)$_n$ clusters, n=3-10 are studied. Using the method of simulated annealing, the geometries of several isomers for each cluster size are examined. Jump-walking Monte Carlo simulations are then used to compute the constant-volume heat capacity for each cluster size over a wide temperature range. To carry out these simulations a new parallel algorithm is developed using the Parallel Virtual Machine (PVM) software package. Features of the cluster potential energy surfaces, such as energy differences among isomers and rotational barriers of the ammonium ions, are found to play important roles in determining the shape of the heat capacity curves.Comment: Journal of Chemical Physics, accepted for publicatio

The presentation, management and outcome of inflammatory breast cancer cases in the UK: data from a multi-centre retrospective review

Objectives: Inflammatory Breast cancer (IBC) is a rare but aggressive form of breast cancer. Its incidence and behaviour in the UK is poorly characterised. We collected retrospective data from hospitals in the UK and Ireland to describe the presentation, pathology, treatment and clinical course of IBC in the UK. Materials and methods: Patients with IBC diagnosed between 1997–2014 at fourteen UK and Irish hospitals were identified from local breast unit databases. Patient characteristics, tumour pathology and stage, and details of surgical, systemic and radiotherapy treatment and follow-up data were collected from electronic patient records and medical notes. Result: This retrospective review identified 445 patients with IBC accounting for 0.4–1.8% of invasive breast cancer cases. Median follow-up was 4.2 years. 53.2% of tumours were grade 3, 56.2% were oestrogen receptor positive, 31.3% were HER2 positive and 25.1% were triple negative. 20.7% of patients had distant metastases at presentation. Despite trimodality treatment in 86.4%, 40.1% of stage III patients developed distant metastases. Five-year overall survival (OS) was 61.0% for stage III and 21.4% for stage IV patients. Conclusions: This is the largest series of UK IBC patients reported to date. It indicates a lower incidence than in American series, but confirms that IBC has a high risk of recurrence with poor survival despite contemporary multi-modality therapy. A national strategy is required to facilitate translational research into this aggressive disease

Recombinant, Live-Attenuated Tetravalent Dengue Virus Vaccine Formulations Induce a Balanced, Broad, and Protective Neutralizing Antibody Response against Each of the Four Serotypes in Rhesus Monkeys

Three tetravalent vaccine (TV) formulations of previously described monovalent dengue (DEN) virus vaccine candidates were compared to a tetravalent formulation of wild-type DEN viruses (T-wt) for replication in SCID mice transplanted with human liver cells (SCID-HuH-7) or for replication and immunogenicity in rhesus monkeys. TV-1 consists of recombinant DEN1, -2, -3, and -4, each with a 30-nucleotide deletion in the 3′ untranslated region (Δ30). TV-2 consists of rDEN1Δ30, rDEN4Δ30, and two antigenic chimeric viruses, rDEN2/4Δ30 and rDEN3/4Δ30, both also bearing the Δ30 mutation. TV-3 consists of rDEN1Δ30, rDEN2Δ30, rDEN4Δ30, and a 10-fold higher dose of rDEN3/4Δ30. TV-1 and TV-2 were attenuated in SCID-HuH-7 mice with minimal interference in replication among the virus components. TV-1, -2, and -3 were attenuated in rhesus monkeys as measured by duration and peak of viremia. Each monkey immunized with TV-1 and TV-3 seroconverted to the four DEN components by day 28 with neutralization titers ranging from 1:52 to 1:273 and 1:59 to 1:144 for TV-1 and TV-3, respectively. TV-2 induced low antibody titers to DEN2 and DEN3, but a booster immunization after 4 months increased the neutralizing antibody titers to greater than 1:100 against each serotype and elicited broad neutralizing activity against 19 of 20 DEN subtypes. A single dose of TV-2 induced protection against wild-type DEN1, DEN3, and DEN4 challenge, but not DEN2. However, two doses of TV-2 or TV-3 induced protection against DEN2 challenge. Two tetravalent formulations, TV-2 and TV-3, possess properties of a successful DEN vaccine and can be considered for evaluation in clinical trials