65 research outputs found
Jamming at Zero Temperature and Zero Applied Stress: the Epitome of Disorder
We have studied how 2- and 3- dimensional systems made up of particles
interacting with finite range, repulsive potentials jam (i.e., develop a yield
stress in a disordered state) at zero temperature and applied stress. For each
configuration, there is a unique jamming threshold, , at which
particles can no longer avoid each other and the bulk and shear moduli
simultaneously become non-zero. The distribution of values becomes
narrower as the system size increases, so that essentially all configurations
jam at the same in the thermodynamic limit. This packing fraction
corresponds to the previously measured value for random close-packing. In fact,
our results provide a well-defined meaning for "random close-packing" in terms
of the fraction of all phase space with inherent structures that jam. The
jamming threshold, Point J, occurring at zero temperature and applied stress
and at the random close-packing density, has properties reminiscent of an
ordinary critical point. As Point J is approached from higher packing
fractions, power-law scaling is found for many quantities. Moreover, near Point
J, certain quantities no longer self-average, suggesting the existence of a
length scale that diverges at J. However, Point J also differs from an ordinary
critical point: the scaling exponents do not depend on dimension but do depend
on the interparticle potential. Finally, as Point J is approached from high
packing fractions, the density of vibrational states develops a large excess of
low-frequency modes. All of these results suggest that Point J may control
behavior in its vicinity-perhaps even at the glass transition.Comment: 21 pages, 20 figure
Partial clustering prevents global crystallization in a binary 2D colloidal glass former
A mixture of two types of super-paramagnetic colloidal particles with long
range dipolar interaction is confined by gravity to a flat interface of a
hanging water droplet. The particles are observed by video microscopy and the
dipolar interaction strength is controlled via an external magnetic field. The
system is a model system to study the glass transition in 2D, and it exhibits
partial clustering of the small particles. This clustering is strongly
dependent on the relative concentration of big and small particles.
However, changing the interaction strength reveals that the clustering
does not depend on the interaction strength. The partial clustering scenario is
quantified using Minkowski functionals and partial structure factors. Evidence
that partial clustering prevents global crystallization is discussed
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
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
A roadmap for Antarctic and Southern Ocean science for the next two decades and beyond
Antarctic and Southern Ocean science is vital to understanding natural variability, the processes
that govern global change and the role of humans in the Earth and climate system. The potential for new
knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic
community came together to ‘scan the horizon’ to identify the highest priority scientific questions that
researchers should aspire to answer in the next two decades and beyond. Wide consultation was a
fundamental principle for the development of a collective, international view of the most important future
directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific
questions through structured debate, discussion, revision and voting. Questions were clustered into seven
topics: i)Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world,
iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond,
and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require
innovative experimental designs, novel applications of technology, invention of next-generation field and
laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating
procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples.
Sustained year-round access toAntarctica and the Southern Ocean will be essential to increase winter-time
measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the
Earth System, and provide predictions at spatial and temporal resolutions useful for decision making.
A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration,
will be essential as no scientist, programme or nation can realize these aspirations alone.Tinker Foundation, Antarctica New Zealand, The New Zealand
Antarctic Research Institute, the Scientific Committee on
Antarctic Research (SCAR), the Council of Managers of
National Antarctic Programs (COMNAP), the Alfred
Wegner Institut, Helmholtz Zentrum für Polar und
Meeresforschung (Germany), and the British Antarctic
Survey (UK).http://journals.cambridge.org/action/displayJournal?jid=ANShb201
The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma
Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival
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
Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics
The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing
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