S.L.A. Marshall and the Ratio of Fire: History, Interpretation, and the Canadian Experience

The famous “ratio of fire” data proposed by S.L.A. Marshall claims that no more than 15-20 percent of soldiers fired their weapons in combat. This article examines whether or not historians can treat Marshall’s ratio of fire data as veracious, and if so what interpretations one can assign to the phenomenon of combat non-participation. The article contends that based upon the Canadian experience it is premature to universalize Marshall’s findings beyond his specific historical subjects, and that studies of human behaviour in war need to look beyond the ratio of fire data as a paradigm for understanding the conduct of soldiers in battle

Review of Canada’s Mechanized Infantry: The Evolution of a Combat Arm, 1920-2012 by Peter Kasurak

Review of Canada’s Mechanized Infantry: The Evolution of a Combat Arm, 1920-2012 by Peter Kasura

Theology, News and Notes - Vol. 36, No. 02

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1103/thumbnail.jp

Theology, News and Notes - Vol. 45, No. 02

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1132/thumbnail.jp

A conserved isoleucine maintains the inactive state of Bruton’s tyrosine kinase

Despite high homology among non-receptor tyrosine kinases, different kinase families employ a diverse array of regulatory mechanisms. For example, the catalytic kinase domains of the Tec family kinases are inactive without assembly of the adjacent regulatory domains, whereas the Src kinase domains are autoinhibited by the assembly of similar adjacent regulatory domains. Using molecular dynamic simulations, biochemical assays, and biophysical approaches, we have uncovered an isoleucine residue in the kinase domain of the Tec family member Btk that, when mutated to the closely related leucine, leads to a shift in the conformational equilibrium of the kinase domain toward the active state. The single amino acid mutation results in measureable catalytic activity for the Btk kinase domain in the absence of the regulatory domains. We suggest this isoleucine side chain in the Tec family kinases acts as a ‘wedge’ that restricts the conformational space available to key regions in the kinase domain, preventing activation until the kinase domain associates with its regulatory subunits and overcomes the energetic barrier to activation imposed by the isoleucine side chain

A Counterexample Regarding Labelled Well-Quasi-Ordering

Korpelainen, Lozin, and Razgon conjectured that a hereditary property of graphs which is well-quasi-ordered by the induced subgraph order and defined by only finitely many minimal forbidden induced subgraphs is labelled well-quasi-ordered, a notion stronger than that of n-well-quasi-order introduced by Pouzet in the 1970s. We present a counterexample to this conjecture. In fact, we exhibit a hereditary property of graphs which is well-quasi-ordered by the induced subgraph order and defined by finitely many minimal forbidden induced subgraphs yet is not 2-well-quasi-ordered. This counterexample is based on the widdershins spiral, which has received some study in the area of permutation patterns

Large-Scale Asset Purchases by the Federal Reserve: Did They Work?

Discusses how the Federal Reserve faced the challenge to further ease the stance of monetary policy as the economic outlook deteriorated through LSAPs

Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism

Ubiquitin specific peptidase 7 (USP7) is a deubiquitinating enzyme (DUB) that removes ubiquitin tags from specific protein substrates in order to alter their degradation rate and sub-cellular localization. USP7 has been proposed as a therapeutic target in several cancers because it has many reported substrates with a role in cancer progression, including FOXO4, MDM2, N-Myc, and PTEN. The multisubstrate nature of USP7, combined with the modest potency and selectivity of early generation USP7 inhibitors, has presented a challenge in defining predictors of response to USP7 and potential patient populations that would benefit most from USP7-targeted drugs. Here, we describe the structureguided development of XL177A, which irreversibly inhibits USP7 with sub-nM potency and selectivity across the human proteome. Evaluation of the cellular effects of XL177A reveals that selective USP7 inhibition suppresses cancer cell growth predominantly through a p53-dependent mechanism: XL177A specifically upregulates p53 transcriptional targets transcriptome-wide, hotspot mutations in TP53 but not any other genes predict response to XL177A across a panel of similar to 500 cancer cell lines, and TP53 knockout rescues XL177A-mediated growth suppression of TP53 wild-type (WT) cells. Together, these findings suggest TP53 mutational status as a biomarker for response to USP7 inhibition. We find that Ewing sarcoma and malignant rhabdoid tumor (MRT), two pediatric cancers that are sensitive to other p53-dependent cytotoxic drugs, also display increased sensitivity to XL177A