179 research outputs found
Coherent information analysis of quantum channels in simple quantum systems
The coherent information concept is used to analyze a variety of simple
quantum systems. Coherent information was calculated for the information decay
in a two-level atom in the presence of an external resonant field, for the
information exchange between two coupled two-level atoms, and for the
information transfer from a two-level atom to another atom and to a photon
field. The coherent information is shown to be equal to zero for all
full-measurement procedures, but it completely retains its original value for
quantum duplication. Transmission of information from one open subsystem to
another one in the entire closed system is analyzed to learn quantum
information about the forbidden atomic transition via a dipole active
transition of the same atom. It is argued that coherent information can be used
effectively to quantify the information channels in physical systems where
quantum coherence plays an important role.Comment: 24 pages, 7 figs; Final versiob after minor changes, title changed;
to be published in Phys. Rev. A, September 200
Theoretical and technological building blocks for an innovation accelerator
The scientific system that we use today was devised centuries ago and is
inadequate for our current ICT-based society: the peer review system encourages
conservatism, journal publications are monolithic and slow, data is often not
available to other scientists, and the independent validation of results is
limited. Building on the Innovation Accelerator paper by Helbing and Balietti
(2011) this paper takes the initial global vision and reviews the theoretical
and technological building blocks that can be used for implementing an
innovation (in first place: science) accelerator platform driven by
re-imagining the science system. The envisioned platform would rest on four
pillars: (i) Redesign the incentive scheme to reduce behavior such as
conservatism, herding and hyping; (ii) Advance scientific publications by
breaking up the monolithic paper unit and introducing other building blocks
such as data, tools, experiment workflows, resources; (iii) Use machine
readable semantics for publications, debate structures, provenance etc. in
order to include the computer as a partner in the scientific process, and (iv)
Build an online platform for collaboration, including a network of trust and
reputation among the different types of stakeholders in the scientific system:
scientists, educators, funding agencies, policy makers, students and industrial
innovators among others. Any such improvements to the scientific system must
support the entire scientific process (unlike current tools that chop up the
scientific process into disconnected pieces), must facilitate and encourage
collaboration and interdisciplinarity (again unlike current tools), must
facilitate the inclusion of intelligent computing in the scientific process,
must facilitate not only the core scientific process, but also accommodate
other stakeholders such science policy makers, industrial innovators, and the
general public
Pathological response and tumour bed histopathological features correlate with survival following neoadjuvant immunotherapy in stage III melanoma
Background: Guidelines for pathological evaluation of neoadjuvant specimens and pathological response categories have been developed by the International Neoadjuvant Melanoma Consortium (INMC). As part of the Optimal Neo-adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo) clinical trial of neoadjuvant combination anti-programmed cell death protein 1/anti-cytotoxic T-Iymphocyte-associated protein 4 immunotherapy for stage III melanoma, we sought to determine interobserver reproducibility of INMC histopathological assessment principles, identify specific tumour bed histopathological features of immunotherapeutic response that correlated with recurrence and relapse-free survival (RFS) and evaluate proposed INMC pathological response categories for predicting recurrence and RFS.Patients and methods: Clinicopathological characteristics of lymph node dissection specimens of 83 patients enrolled in the OpACIN-neo clinical trial were evaluated. Two methods of assessing histological features of immunotherapeutic response were evaluated: the previously described immune-related pathologic response (irPR) score and our novel immunotherapeutic response score (ITRS). For a subset of cases (n = 29), cellular composition of the tumour bed was analysed by flow cytometry.Results: There was strong interobserver reproducibility in assessment of pathological response (kappa = 0.879) and percentage residual viable melanoma (intraclass correlation coefficient = 0.965). The immunotherapeutic response subtype with high fibrosis had the strongest association with lack of recurrence (P = 0.008) and prolonged RFS (P = 0.019). Amongst patients with criteria for pathological non-response (pNR, >50% viable tumour), all who recurred had >= 70% viable melanoma. Higher ITRS and irPR scores correlated with lack of recurrence in the entire cohort (P = 0.002 and P = 70% viable melanoma and incorporating additional criteria of <10% fibrosis subtype of response may identify those at highest risk of recurrence, but requires validation.Analysis and support of clinical decision makin
Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma
Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN () and phase 2 OpACIN-neo () studies(1,2). While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P < 0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-gamma score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-gamma score/high TMB; patients with high IFN-gamma score/low TMB or low IFN-gamma score/high TMB had pRRs of 91% and 88%; while patients with low IFN-gamma score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-gamma score. Our findings provide a strong rationale for a randomized phase 3 study comparing neoadjuvant ipilimumab plus nivolumab versus standard adjuvant therapy with antibodies against the programmed cell death protein-1 (anti-PD-1) in macroscopic stage III melanoma
Novel genetic loci associated with hippocampal volume
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness
Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy
Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET
The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR
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