Granitic Domes of the Mohave Desert, California

Several granitic areas in the Mohave Desert region of southeastern California have been degraded to smooth dome-like forms, to which Lawson has given the name, panfans. They have diameters of from 3 to 6 or 8 miles and heights of from 500 to 2,000 feet over the adjacent lower land. One of the best examples is shown in Plate 12. The well graded convexity of these masses, the steepest declivity of which seldom measures more than 4° or 5°, is flanked by the long, aggraded, concave slopes of their detritus. In some instances the domes are elongated into arches, 10 or 15 miles in length. Many other areas, granitic and non-granitic, less completely and less symmetrically degraded, exhibit bold or subdued residual forms surmounting their smoothly degraded flanks. The most perfect domes or arches result from the undisturbed degradation of upheaved granitic masses which have been worked upon, according to their original form, 1 chiefly by one or the other of two somewhat unlike erosional processes, both of which are merely modifications of ordinary erosional processes appropriate to the dry climate where their action takes place

The Lakes of California

The forms of the lands are determined in the main by the slow interaction of two antagonistic processes. One process, of interior origin and unsolved explanation, slowly deforms the earth’s crust and makes its surface uneven. Associated with this deforming process in being of interior origin and of difficult explanation, but apparently acting independently of it, are volcanic eruptions which build up cones and domes and pour out lava flows of smaller or larger extent

The Ursinus Weekly, April 25, 1938

Coeds choose Lees, Poling, Claflin leaders • Harrisburg group hears Ade, Toll at conclave • Dictators main peace threat say conference leaders • Plays Saturday night week-end feature • May sports hop makes lucky Friday 13 • Wimer new YM head; appoints cabinet • Alumnus develops Sweden in Forefathers address • Stoudt, Craigie to play leads in First lady • Girls hear vocation charts by career women • Embryo lawyers discuss organization of club • Mikado again in rehearsal • Temple leads • Charm, attractiveness, especially a mysterious allurement • Musical variety features club\u27s Easter program • Pre-meds to hear Dr. Eger at next week\u27s meeting • Clawson addresses Berks County math club • Sheeder, Old, Ursinus visit Lansdale, Camden schools • Batsmen beat Lehigh, but lose to Lafayette • Stine close victory in intramural tourney • Cindermen place third in meet at Drexel • Ware\u27s racketeers down Bryn Mawr Sat. 3-2 • \u27Sinus second college in U.S. with cricket team • Hill defeats bear J.V.s 9-5; meet Villanova today • Musical organizations hold concert in Bomberger • Witmer addresses faculty club at April meeting • Frosh parade makes College Humor • Women end forensic season • Baird, Martin, DeWire to enter graduate schools • Biology students spend week-end in New York • Ursinus line coach to wed during football seasonhttps://digitalcommons.ursinus.edu/weekly/1897/thumbnail.jp

The Ursinus Weekly, May 16, 1938

College to confer two honorary degrees • Y\u27s invite students, profs to spring doggie roast • Loan fund established by Varsity Club • 110 couples dance Friday at May sports hop • Stoudt, Plunkett star in Mother\u27s Day play; pageant, dinner other Saturday activities • Glatfelter chosen to head men\u27s council • Ursinus gains victory over Penn on radio • McClure, Poling speak at two Sunday vespers • June issue of Lantern to feature commencement • Presenting the \u27sinus senior: a preview of the 1938 Ruby questionnaire • Works of contemporary Philadelphia painters displayed in exhibit • Bears trim Albright, Gettysburg in league tilts • Trackmen poor fifth in Lancaster meet • Records broken as school trackmen meet here • Peg Claflin installed as new WAA head • Power leads batsmen • Todt succeeds Bodley as Varsity Club leader • Curtain clubbers dine and dance in Norristown • Power elected president of pre-legal society • Laucks conducts current events quiz of IRC • Germantown boy awarded sixth open scholarshiphttps://digitalcommons.ursinus.edu/weekly/1900/thumbnail.jp

Bostonia: The Boston University Alumni Magazine. Volume 10

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Ernst Freund as Precursor of the Rational Study of Corporate Law

Gindis, David, Ernst Freund as Precursor of the Rational Study of Corporate Law (October 27, 2017). Journal of Institutional Economics, Forthcoming. Available at SSRN: https://ssrn.com/abstract=2905547, doi: https://dx.doi.org/10.2139/ssrn.2905547The rise of large business corporations in the late 19th century compelled many American observers to admit that the nature of the corporation had yet to be understood. Published in this context, Ernst Freund's little-known The Legal Nature of Corporations (1897) was an original attempt to come to terms with a new legal and economic reality. But it can also be described, to paraphrase Oliver Wendell Holmes, as the earliest example of the rational study of corporate law. The paper shows that Freund had the intuitions of an institutional economist, and engaged in what today would be called comparative institutional analysis. Remarkably, his argument that the corporate form secures property against insider defection and against outsiders anticipated recent work on entity shielding and capital lock-in, and can be read as an early contribution to what today would be called the theory of the firm.Peer reviewe

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module

The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub-domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand-bound CBMs suggest that EmbCCT contains two separate carbohydrate binding sites, associated with subdomains I and II, respectively. Single-residue substitution of conserved tryptophan residues (Trp868, Trp985) at these respective sites inhibited EmbC-catalysed extension of LAM. The same substitutions differentially abrogated binding of di- and penta-arabinofuranoside acceptor analogues to EmbCCT, linking the loss of activity to compromised acceptor substrate binding, indicating the presence of two separate carbohydrate binding sites, and demonstrating that subdomain II indeed functions as a carbohydrate-binding module. This work provides the first step towards unravelling the structure and function of a GT-C-type glycosyltransferase that is essential in M. tuberculosis. Author Summary Top Tuberculosis (TB), an infectious disease caused by the bacillus Mycobacterium tuberculosis, burdens large swaths of the world population. Treatment of active TB typically requires administration of an antibiotic cocktail over several months that includes the drug ethambutol. This front line compound inhibits a set of arabinosyltransferase enzymes, called EmbA, EmbB and EmbC, which are critical for the synthesis of arabinan, a vital polysaccharide in the pathogen's unique cell envelope. How precisely ethambutol inhibits arabinosyltransferase activity is not clear, in part because structural information of its pharmacological targets has been elusive. Here, we report the high-resolution structure of the C-terminal domain of the ethambutol-target EmbC, a 390-amino acid fragment responsible for acceptor substrate recognition. Combining the X-ray crystallographic analysis with structural comparisons, site-directed mutagenesis, activity and ligand binding assays, we identified two regions in the C-terminal domain of EmbC that are capable of binding acceptor substrate mimics and are critical for activity of the full-length enzyme. Our results begin to define structure-function relationships in a family of structurally uncharacterised membrane-embedded glycosyltransferases, which are an important target for tuberculosis therapy

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN