Bottom Quark Cross Sections at Collider and Fixed-Target Energies at the SSC and LHC

Calculations of inclusive cross sections for the production of bottom quarks in proton-proton collisions are presented as a function of energy, transverse momentum, and Feynman $x_F$ for values of $\sqrt{s}$ from $100~$GeV to $40~$TeV. In addition, we provide simple parametrizations of our theoretical results that should facilitate estimates of rates, acceptances, and efficiencies of proposed new detectors.Comment: 6 pages plus 11 topdraw figures appended as ps-files(uuencoded), Latex, ANL-HEP-CP-93-63 & CERN-TH.6987/9

Generalized MICZ-Kepler Problems and Unitary Highest Weight Modules

For each integer $n\ge 1$, we demonstrate that a $(2n+1)$-dimensional generalized MICZ-Kepler problem has an \mr{Spin}(2, 2n+2) dynamical symmetry which extends the manifest \mr{Spin}(2n+1) symmetry. The Hilbert space of bound states is shown to form a unitary highest weight \mr{Spin}(2, 2n+2)-module which occurs at the first reduction point in the Enright-Howe-Wallach classification diagram for the unitary highest weight modules. As a byproduct, we get a simple geometric realization for such a unitary highest weight \mr{Spin}(2, 2n+2)-module.Comment: 27 pages, Refs. update

Transverse Momentum Distributions for Heavy Quark Pairs

We study the transverse momentum distribution for a $pair$ of heavy quarks produced in hadron-hadron interactions. Predictions for the large transverse momentum region are based on exact order $\alpha_s^3$ QCD perturbation theory. For the small transverse momentum region, we use techniques for all orders resummation of leading logarithmic contributions associated with initial state soft gluon radiation. The combination provides the transverse momentum distribution of heavy quark pairs for all transverse momenta. Explicit results are presented for $b\bar b$ pair production at the Fermilab Tevatron collider and for $c\bar c$ pair production at fixed target energies.Comment: LaTeX (27 pages text, 8 figures not included, but available on request

Spatial and temporal clonal evolution of intrahepatic cholangiocarcinoma

Background & Aims: Intrahepatic cholangiocarcinoma (ICC) is the second-most lethal primary liver cancer. Little is known about intratumoral heterogeneity (ITH) and its impact on ICC progression. We aim to investigate its ITH in hope of helping develop new therapeutic strategies. Methods: We obtained 69 spatially distinct regions from 6 operable ICCs. Patient-derived primary cancer cells (PDPCs) were established for each region, followed by whole-exome sequencing(WES) and multi-level validation. Results: We observed widespread ITH for both somatic mutations and clonal architecture, shaped by multiple mechanisms, like clonal “illusion”, parallel evolution and chromosome instability. A median of 60.3% mutations were heterogeneous mutations, among which 85% of the driver mutations located on the branches of tumor phylogenetic trees. Many truncal and clonal driver mutations occurred in tumor-suppressor genes, such as TP53, SMARCB1 and PBRM1 that involved in DNA repair and chromatin-remodeling. Genome doubling occurred in most cases (5/6) after the accumulation of truncal mutations and was shared by all intratumoral subregions. In all cases, ongoing chromosomal instability is evident throughout the evolutionary trajectory of ICC. The recurrence of ICC1239 provided evidence to support the polyclonal metastatic seeding in ICC. The change of mutation landscape and internal diversity among subclones during metastasis, such as the loss of chemoresistance mediator, may be used for new treatment strategy. Targeted therapy against truncal alterations, such as IDH1, JAK1, and KRAS mutations and EGFR amplification, could be developed in 5/6 patients. Conclusions: Integrated investigations of spatial ITH and clonal evolution may provide an important molecular foundation for enhanced understanding of tumorigenesis and progression in ICC. Lay summary: We applied multiregional whole exome sequencing to investigate the evolution trajectory of ICC. The results revealed that many fuels, such as parallel evolution and chromosome instability, may participate and promote the branch diversity of ICC. Interestingly, in one patient with primary and recurrent metastatic tumors, we found some clues of polyclonal metastatic seeding, indicating that symbiotic communities of multiple clones existed and were maintained during metastasis. More realistically, some truncal alterations, such as IDH1, JAK1, and KRAS mutations and EGFR amplification, can be promising treatment targets for ICC patients

Biotransformation of rare earth oxide nanoparticles eliciting microbiota imbalance

Background Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. Results This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G−) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G− and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G− cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G−/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G−/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. Conclusions This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G− and G+ bacteria and disclosed that La2O3-induced membrane damages of G− cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies