The gravity field of Sundaland: acquisition, assessment and interpretation

The 1995 Sandwell & Smith WGI7.2 satellite gravity map has been compared with high quality ship gravity data offshore Sabah. The standard deviation of the differences between gravity profiles interpolated from WGI7.2 and the ship survey was 5.7 mGal. Spectral analysis indicated that WGI7.2 resolves features with half-wavelengths greater than 10 km. Three hundred new gravity stations, including ten base stations tied to IGSN71, were established during a survey of Sabah and were merged with two previous surveys to complete the gravity coverage of the state at reconnaissance level. New gravity maps of Sundaland, compiled from the Sabah and WGI7.2 gravity data sets have been interpreted. ' Subtraction from these data sets of the long wavelength GEM-T3 gravity anomaly field, which is dominated by the effects of the subducted proto-South China Sea and the ongoing subduction of the Australian, Indian and Philippine Sea Plates, achieved a simple 'regional-residual' separation and the isolation of crustal-scale anomalies. 5' x 5' maps of the depth to Moho, crustal thickness and β (crustal extension) factor beneath the Sunda Shelf and the South China Sea have been produced by 1-D geometric manipulation of the marine gravity field using sediment isopach and bathymetry control data. The average difference between the new Moho map and seismic refraction depth-to-Moho estimates at the south China margin was 0.2 ± 2.0 km. The Moho rises from an average depth of 29 km beneath the Sunda Shelf to a depth of about 16 km beneath the South China Sea oceanic basin. It is estimated that approximately 1100 km of oceanic crust of the proto-South China Sea was subducted at the northwest Borneo margin. Gravity modelling independently confirmed the average 35 mm/yr spreading rate prediction for the southwestern subbasin of the South China Sea oceanic basin from magnetic lineation interpretation. Quantitative interpretation indicates that Sabah is underlain by thick continental crust, and gravity modelling of the Maliau Basin predicts a minimum sediment thickness of 8 km. The ophiolite bodies at Telupid and Darvel Bay are separated by a gravity low and there is no evidence that the two are related. The crustal root of the Crocker Ranges extends to a depth of ~49 km below sea level. In order to reach this present day crustal thickness, the turbiditic sediments forming the Crocker Ranges must have been compressed to less than half of their original lateral extent during the Sabah Orogeny

Absolute wave-number measurements in 130Te2: Reference lines spanning the 420.9-464.6-nm region

We have measured the absolute wave numbers of 39 transitions of 130Te2 spanning the spectral region of 420.9-464.6 nm to an accuracy of better than 2 parts in 109 by use of saturation spectroscopy and Fabry-Pérot interferometry. These measurements provide a set of convenient and accurate transfer standards for laser wavelength calibration spanning the entire Stilbene-420 dye-tuning curve

Characteristics of TCR repertoire associated with successful immune checkpoint therapy responses

Immunotherapies have revolutionized cancer treatment. In particular, immune checkpoint therapy (ICT) leads to durable responses in some patients with some cancers. However, the majority of treated patients do not respond. Understanding immune mechanisms that underlie responsiveness to ICT will help identify predictive biomarkers of response and develop treatments to convert non-responding patients to responding ones. ICT primarily acts at the level of adaptive immunity. The specificity of adaptive immune cells, such as T and B cells, is determined by antigen-specific receptors. T cell repertoires can be comprehensively profiled by high-throughput sequencing at the bulk and single-cell level. T cell receptor (TCR) sequencing allows for sensitive tracking of dynamic changes in antigen-specific T cells at the clonal level, giving unprecedented insight into the mechanisms by which ICT alters T cell responses. Here, we review how the repertoire influences response to ICT and conversely how ICT affects repertoire diversity. We will also explore how changes to the repertoire in different anatomical locations can better correlate and perhaps predict treatment outcome. We discuss the advantages and limitations of current metrics used to characterize and represent TCR repertoire diversity. Discovery of predictive biomarkers could lie in novel analysis approaches, such as network analysis of amino acids similarities between TCR sequences. Single-cell sequencing is a breakthrough technology that can link phenotype with specificity, identifying T cell clones that are crucial for successful ICT. The field of immuno-sequencing is rapidly developing and cross-disciplinary efforts are required to maximize the analysis, application, and validation of sequencing data. Unravelling the dynamic behavior of the TCR repertoire during ICT will be highly valuable for tracking and understanding anti-tumor immunity, biomarker discovery, and ultimately for the development of novel strategies to improve patient outcomes

Development of an acceptable and feasible self-management group for children, young people and families living with Type 1 diabetes.

AIMS: This study developed an acceptable and feasible self-management intervention that addresses the self-identified needs of children and young people with Type 1 diabetes and their parents. METHODS: Phase 1 reviewed previous interventions and interviewed the clinical team, young people and families. Phase 2 ran three age-matched focus groups with 11 families of children aged 8-16 years. Feedback was used to modify the workshop. Phase 3 evaluated feasibility of delivery, as well as the effects on metabolic control, quality of life and fear of hypoglycaemia, measured at baseline and 1-3 months post intervention. RESULTS: Eighty-nine families were invited to take part. Twenty-two (25%) participated in seven pilot groups (median age of young people 10 years, 36% girls). The intervention comprised a developmentally appropriate workshop for young people and parents addressing: (1) blood glucose control, (2) the potential impact of long-term high HbA1c , (3) the effects of 'hypos' and 'hypers', (4) self-management techniques and (5) talking confidently to people about diabetes. Participants were enthusiastic and positive about the workshop and would recommend it to others. Young people liked sharing ideas and meeting others with diabetes, while parents enjoyed listening to their children talk about their diabetes knowledge. CONCLUSIONS: Families living with Type 1 diabetes participated in developing a self-management group intervention. Although we demonstrated acceptability and feasibility, the pilot study results do not support the development of a randomized control trial to evaluate the effectiveness in improving HbA1c

The helium trimer with soft-core potentials

The helium trimer is studied using two- and three-body soft-core potentials. Realistic helium-helium potentials present an extremely strong short-range repulsion and support a single, very shallow, bound state. The description of systems with more than two helium atoms is difficult due to the very large cancellation between kinetic and potential energy. We analyze the possibility of describing the three helium system in the ultracold regime using a gaussian representation of a widely used realistic potential, the LM2M2 interaction. However, in order to describe correctly the trimer ground state a three-body force has to be added to the gaussian interaction. With this potential model the two bound states of the trimer and the low energy scattering helium-dimer phase shifts obtained with the LM2M2 potential are well reproduced.Comment: 15 pages, 3 figures, submitted to Few-Body System

Tumor infiltrating effector memory Antigen-Specific CD8+ T Cells predict response to immune checkpoint therapy

Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT. We tracked tumor antigen-specific CTL frequencies and phenotype before and after ICT in responding and non-responding animals. Tumor antigen-specific CTLs increased within tumor and draining lymph nodes after ICT, and exhibited an effector memory-like phenotype, expressing IL-7R (CD127), KLRG1, T-bet, and granzyme B. Responding tumors exhibited higher infiltration of effector memory tumor antigen-specific CTLs, but lower frequencies of regulatory T cells compared to non-responders. Tumor antigen-specific CTLs persisted in responding animals and formed memory responses against tumor antigens. Our results suggest that increased effector memory tumor antigen-specific CTLs, in the presence of reduced immunosuppression within tumors is part of a successful ICT response. Temporal and nuanced analysis of T cell subsets provides a potential new source of immune based biomarkers for response to ICT

A-dependence of nuclear transparency in quasielastic A(e,e'p) at high Q^2

The A-dependence of the quasielastic A(e,e'p) reaction has been studied at SLAC with H-2, C, Fe, and Au nuclei at momentum transfers Q^2 = 1, 3, 5, and 6.8 (GeV/c)^2. We extract the nuclear transparency T(A,Q^2), a measure of the average probability that the struck proton escapes from the nucleus A without interaction. Several calculations predict a significant increase in T with momentum transfer, a phenomenon known as Color Transparency. No significant rise within errors is seen for any of the nuclei studied.Comment: 5 pages incl. 2 figures, Caltech preprint OAP-73

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Search for composite and exotic fermions at LEP 2

A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio