Riverine sustainment 2012

Student Integrated ProjectIncludes supplementary materialThis technical report analyzed the Navy's proposed Riverine Force (RF) structure and capabilities for 2012. The Riverine Sustainment 2012 Team (RST) examined the cost and performance of systems of systems which increased RF sustainment in logistically barren environments. RF sustainment was decomposed into its functional areas of supply, repair, and force protection. The functional and physical architectures were developed in parallel and were used to construct an operational architecture for the RF. The RST used mathematical, agent-based and queuing models to analyze various supply, repair and force protection system alternatives. Extraction of modeling data revealed several key insights. Waterborne heavy lift connectors such as the LCU-2000 are vital in the re-supply of the RF when it is operating up river in a non-permissive environment. Airborne heavy lift connectors such as the MV-22 were ineffective and dominated by the waterborne variants in the same environment. Increase in manpower and facilities did appreciable add to the operational availability of the RF. Mean supply response time was the biggest factor effecting operational availability and should be kept below 24 hours to maintain operational availability rates above 80%. Current mortar defenses proposed by the RF are insufficient.N

Complete Ichthyornis skull illuminates mosaic assembly of the avian head

The skull of living birds is greatly modified from the condition found in their dinosaurian antecedents. Bird skulls have an enlarged, toothless premaxillary beak and an intricate kinetic system that includes a mobile palate and jaw suspensorium. The expanded avian neurocranium protects an enlarged brain and is flanked by reduced jaw adductor muscles. However, the order of appearance of these features and the nature of their earliest manifestations remain unknown. The Late Cretaceous toothed bird Ichthyornis dispar sits in a pivotal phylogenetic position outside living groups: it is close to the extant avian radiation but retains numerous ancestral characters 1-3. Although its evolutionary importance continues to be affirmed 3-8, no substantial new cranial material of I. dispar has been described beyond incomplete remains recovered in the 1870s. Jurassic and Cretaceous Lagerstatten have yielded important avialan fossils, but their skulls are typically crushed and distorted 9. Here we report four three-dimensionally preserved specimens of I. dispar- including an unusually complete skull-as well as two previously overlooked elements from the Yale Peabody Museum holotype, YPM 1450. We used these specimens to generate a nearly complete three-dimensional reconstruction of the I. dispar skull using highresolution computed tomography. Our study reveals that I. dispar had a transitional beak-small, lacking a palatal shelf and restricted to the tips of the jaws-coupled with a kinetic system similar to that of living birds. The feeding apparatus of extant birds therefore evolved earlier than previously thought and its components were functionally and developmentally coordinated. The brain was relatively modern, but the temporal region was unexpectedly dinosaurian: it retained a large adductor chamber bounded dorsally by substantial bony remnants of the ancestral reptilian upper temporal fenestra. This combination of features documents that important attributes of the avian brain and palate evolved before the reduction of jaw musculature and the full transformation of the beak. </p

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models

Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models. PDX-MI defines the minimal information for describing the clinical attributes of a patient's tumor, the processes of implantation and passaging of tumors in a host mouse strain, quality assurance methods, and the use of PDX models in cancer research. Adherence to PDX-MI standards will facilitate accurate search results for oncology models and their associated data across distributed repository databases and promote reproducibility in research studies using these models. Cancer Res; 77(21); e62-66. ©2017 AAC

Market Knowledge Dimensions and Cross-Functional Collaboration: Examining the Different Routes to Product Innovation Performance

There is consensus in the marketing literature that market knowledge and cross-functional collaboration are two fundamental resources for successful product innovation. However, few studies examine the dimensions or characteristics of market knowledge and how and why these resources influence product innovation performance. Drawing on contingency theory and the knowledge-based view of the firm, the authors argue that knowledge integration mechanisms may account for the effects of market knowledge dimensions (i.e., breadth, depth, tacitness, and specificity) and cross-functional collaboration on product innovation performance. They find that market knowledge specificity and cross-functional collaboration affect product innovation performance through knowledge integration mechanisms. In contrast, whereas the effect of market knowledge depth is partially mediated, market knowledge breadth has a direct, unmediated effect on product innovation performance. A test of an alternative moderating perspective shows that the effects of market knowledge depth and cross-functional collaboration on product innovation are negatively moderated by knowledge integration mechanisms. By showing the differential effects of market knowledge dimensions on product innovation performance, the authors provide a more refined understanding of the interplay among market knowledge, its integration, and the firm's performance in product innovation. The authors also conclude that by overlooking the role of knowledge integration mechanisms, previous research may have provided an overly optimistic view of the value of cross-functional collaboration in product innovation