80 research outputs found
Crystalline Assemblies and Densest Packings of a Family of Truncated Tetrahedra and the Role of Directional Entropic Forces
Polyhedra and their arrangements have intrigued humankind since the ancient
Greeks and are today important motifs in condensed matter, with application to
many classes of liquids and solids. Yet, little is known about the
thermodynamically stable phases of polyhedrally-shaped building blocks, such as
faceted nanoparticles and colloids. Although hard particles are known to
organize due to entropy alone, and some unusual phases are reported in the
literature, the role of entropic forces in connection with polyhedral shape is
not well understood. Here, we study thermodynamic self-assembly of a family of
truncated tetrahedra and report several atomic crystal isostructures, including
diamond, {\beta}-tin, and high- pressure lithium, as the polyhedron shape
varies from tetrahedral to octahedral. We compare our findings with the densest
packings of the truncated tetrahedron family obtained by numerical compression
and report a new space filling polyhedron, which has been overlooked in
previous searches. Interestingly, the self-assembled structures differ from the
densest packings. We show that the self-assembled crystal structures can be
understood as a tendency for polyhedra to maximize face-to-face alignment,
which can be generalized as directional entropic forces.Comment: Article + supplementary information. 23 pages, 10 figures, 2 table
1960: Abilene Christian College Lectures - Full Text
Table of Contents:
Theme Speeches: Christian Faith in the Modern World
Basis of Faith - Leonard Mullens - 9
Authority in Christianity - John T. Smithson, Jr. - 27
Origin and Preservation of the Bible - Neil R. Lightfoot - 44
Alleged Discrepancies of the Bible - David H. Bobo - 62
The Unity of the Bible - Jack Meyer - 91
Faith and Reason - Joe Sanders - 115
The Reasonableness of Supernaturalism - Virgil Trout - 126
The Present Statue of the Doctrine of Organic Evolution - J.D. Thomas - 146
The Nature of Man - Roy F. Osborne, Jr. - 181
Modern Challenges to Christian Morals - Carl Spain - 199
The Christ, Whose Son is He? - Gordon Teel - 232
Special Speeches
Teaching the Word of God in Korea - L. Haskell Chessfire - 255
The Influence of Christian Education - Judge Jack Pope - 276
Mission Opportunities in the Far East - Harry Robert Fox - 288
Mission Work in Austria - Robert Skelton - 303
Report from Switzerland - Heinrich Blum - 313
The Work in Nigeria - Rees Byrant - 320
The Training of Evangelists in Foreign Fields - Reiner Kallus - 331
Christian Scholarships - Everett Ferguson - 340
Evangelizing the World - A.R. Holton - 349
Panel Discussions
The Significance of the Dead Sea Scrolls
The Scrolls and the Text of the Bible - Paul Rotenberry - 357
The Relation between the Religion of the Essenes and that of Early Christians - Jay Smith - 366
Biblical Interpretation
Expediency and Pattern Authority - J.W. Roberts - 381
Examples in Pattern Authority - Thomas B. Warren - 392
Mental Health and Sin
The Present State of Mental Health Knowledge - Donald R. Sime - 409
The Relationship of Mental Health Problems to Sin - Paul Easley - 421
The Teenager
The Problems of Youth - Mack Wayne Craig - 432
Influences for Good - Wyatt Sawyer - 443
The Benefits of Abilene Christian College
To the Church - Hulen Jackson - 451
To The Home - Robert S. Bell - 459
\u27To the Community - Louie Welch - 465
Expenses At Abilene Christian College - James C. Kerr - 469
The Graduate School at Abilene Christian College
What I Am Getting Now in the ACC Graduate Program - Harold Vanderpool - 475
How the ACC Graduate Program Has Stood Up - Everett Ferguson - 481
What the ACC Graduate Program Ought To Be - Frank Pack - 486
The Importance to the Church of the ACC Graduate Program A.R. Holton - 490
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Microbial Reprogramming Inhibits Western Diet-Associated Obesity
A recent epidemiological study showed that eating âfast foodâ items such as potato chips increased likelihood of obesity, whereas eating yogurt prevented age-associated weight gain in humans. It was demonstrated previously in animal models of obesity that the immune system plays a critical role in this process. Here we examined human subjects and mouse models consuming Westernized âfast foodâ diet, and found CD4[superscript +] T helper (Th)17-biased immunity and changes in microbial communities and abdominal fat with obesity after eating the Western chow. In striking contrast, eating probiotic yogurt together with Western chow inhibited age-associated weight gain. We went on to test whether a bacteria found in yogurt may serve to lessen fat pathology by using purified Lactobacillus reuteri ATCC 6475 in drinking water. Surprisingly, we discovered that oral L. reuteri therapy alone was sufficient to change the pro-inflammatory immune cell profile and prevent abdominal fat pathology and age-associated weight gain in mice regardless of their baseline diet. These beneficial microbe effects were transferable into naĂŻve recipient animals by purified CD4[superscript +] T cells alone. Specifically, bacterial effects depended upon active immune tolerance by induction of Foxp3[superscript +] regulatory T cells (Treg) and interleukin (Il)-10, without significantly changing the gut microbial ecology or reducing ad libitum caloric intake. Our finding that microbial targeting restored CD4[superscript +] T cell balance and yielded significantly leaner animals regardless of their dietary âfast foodâ indiscretions suggests population-based approaches for weight management and enhancing public health in industrialized societies.National Institutes of Health (U.S.) (Grant P30-ES002109)National Institutes of Health (U.S.) (Grant RO1CA108854)National Institutes of Health (U.S.) (Grant P01 AI045757)National Institutes of Health (U.S.) (Grant U19 AI046130)National Institutes of Health (U.S.) (Grant U19 AI070352)National Institutes of Health (U.S.) (Grant P01 AI039671)National Institute of Neurological Disorders and Stroke (U.S.) (Jacob Javits Merit Award NS2427)The Penates FoundationNancy Taylor Foundation for Chronic Diseases, Inc
Receptor Tyrosine Kinases in Osteosarcoma: 2019 Update
The primary conclusions of our 2014 contribution to this series were as follows:
Multiple receptor tyrosine kinases (RTKs) likely contribute to aggressive phenotypes in osteosarcoma and, therefore, inhibition of multiple RTKs is likely necessary for successful clinical outcomes.
Inhibition of multiple RTKs may also be useful to overcome resistance to inhibitors of individual RTKs as well as resistance to conventional chemotherapies.
Different combinations of RTKs are likely important in individual patients.
AXL, EPHB2, FGFR2, IGF1R, and RET were identified as promising therapeutic targets by our in vitro phosphoproteomic/siRNA screen of 42 RTKs in the highly metastatic LM7 and 143B human osteosarcoma cell lines.
This chapter is intended to provide an update on these topics as well as the large number of osteosarcoma clinical studies of inhibitors of multiple tyrosine kinases (multi-TKIs) that were recently published
From RealâWorld Patient Data to Individualized Treatment Effects Using Machine Learning: Current and Future Methods to Address Underlying Challenges
D-glucose as a multivalent chiral scaffold for combinatorial chemistry
Due to their high density of functional groups and their availability in a variety of diastereomeric forms, monosaccharides are considered attractive scaffolds for combinatorial chemistry that allow the attachment and defined spatial alignment of up to five different pharmacophoric groups. For their application in combinatorial syntheses on solid phase, a set of selectively removable hydroxy protecting groups in combination with a cleavable anchor is required. Herein, we report on the construction and use of a versatile multivalent glucose building block for parallel synthesis on the solid phase. (C) 2002 Elsevier Science Ltd. All rights reserved
Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer
Background: Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. Methods: 3-dimensional fluorescence spectroscopy was conducted to asses cell-free nintedanib fluorescence properties. MTT assay was used to determine the impact of the lysosome-targeting agents bafilomycin A1 and chloroquine combined with nintedanib on lung cancer cell viability. Flow cytometry and live cell as well as confocal microscopy were performed to analyze uptake kinetics as well as subcellular distribution of nintedanib. Western blot was conducted to investigate protein expression. Cryosections of subcutaneous tumor allografts were generated to detect intratumoral nintedanib in mice after oral drug administration. Results: Here, we report for the first time drug-intrinsic fluorescence properties of nintedanib in living and fixed cancer cells as well as in cryosections derived from allograft tumors of orally treated mice. Using this feature in conjunction with flow cytometry and confocal microscopy allowed to determine cellular drug accumulation levels, impact of the ABCB1 efflux pump and to uncover nintedanib trapping into lysosomes. Lysosomal sequestration - resulting in an organelle-specific and pH-dependent nintedanib fluorescence - was identified as an intrinsic resistance mechanism in FGFR-driven lung cancer cells. Accordingly, combination of nintedanib with agents compromising lysosomal acidification (bafilomycin A1, chloroquine) exerted distinctly synergistic growth inhibitory effects. Conclusion: Our findings provide a powerful tool to dissect molecular factors impacting organismal and intracellular pharmacokinetics of nintedanib. Regarding clinical application, prevention of lysosomal trapping via lysosome-alkalization might represent a promising strategy to circumvent cancer cell-intrinsic nintedanib resistance
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