The Other SiO2: Investigating Oxidation of Alcohols Using (NH4)2Cr2O7 in Sand

Oxidation of alcohols to aldehydes and ketones is one of the classical reactions in organic chemistry which is utilized frequently in medicine, industry, and pharmaceuticals. Classical effective reagents in oxidation include pyridinium chlorochromate, potassium permanganate, Jones reagent, bleach, and Swern conditions. There has been an increasing interest throughout the years to use supported-based reagents in tandem with these reagents, particularly with silica gel especially towards Cr-based oxidizing agents. Despite the abundance of reported reactions in the literature pertaining to silica gel, little is known about sand, despite both are silicon dioxide and exhibit similar porosity and crystallinity. It is not clear as why silica gel is frequently used in chemical reactions compared to sand. Herein, we report some of our results regarding the utilization of washed sand in oxidation of primary and secondary alcohols. Using an appropriate solvent under reflux, primary and secondary alcohols are oxidized cleanly into aldehydes and ketones based on TLC monitoring and 1H and 13C-NMR of the crude material. More importantly, reactions can be carried out in lower reagent loading compared to silica-gel based oxidations

174— Developing Oxidation of Alcohols in Sand

We present the oxidation of alcohols into aldehydes and ketones using (NH4)2Cr2O7 in sand. Several alcohols undergo oxidation using an appropriate solvent to afford aldehyde and ketones in good yields. The reactions were analyzed by TLC, 1H and 13C-NMR. The developed reaction is also compared to reactions done using silica gel

Observations on Expedited Systems Engineering Practices in Military Rapid Development Projects

This research, conducted in the Systems Engineering Research Center (SERC), examined systems engineering and engineering management practices for military rapid capability and urgent needs programs. Lifecycle of urgent needs programs is driven by “time to market” as opposed to complete satisfaction of static requirements, with delivery expected in months versus years/decades. The processes and practices applied to urgent needs must add value and not require an excessive bureaucratic oversight to implement, while at the same time address, understand, and manage risk such that programs can understand better where to include, truncate, eliminate, tailor, or scale systems engineering practices and processes. Focusing on aspects of the product, process, and people of military rapid organizations, the analysis showed that these organizations have the right team, develop innovative conceptual solutions, quickly prune the design space, and identify appropriate designs that can deliver warfighting capability expeditiously. While these observations may not seem new, they provide the foundation for a broader framework of rapid development, which is the subject of ongoing research

Observations on Expedited Systems Engineering Practices in Military Rapid Development Projects

This research, conducted in the Systems Engineering Research Center (SERC), examined systems engineering and engineering management practices for military rapid capability and urgent needs programs. Lifecycle of urgent needs programs is driven by “time to market” as opposed to complete satisfaction of static requirements, with delivery expected in months versus years/decades. The processes and practices applied to urgent needs must add value and not require an excessive bureaucratic oversight to implement, while at the same time address, understand, and manage risk such that programs can understand better where to include, truncate, eliminate, tailor, or scale systems engineering practices and processes. Focusing on aspects of the product, process, and people of military rapid organizations, the analysis showed that these organizations have the right team, develop innovative conceptual solutions, quickly prune the design space, and identify appropriate designs that can deliver warfighting capability expeditiously. While these observations may not seem new, they provide the foundation for a broader framework of rapid development, which is the subject of ongoing research

Adaptability of a Catalog Spacecraft Bus to Diverse Science Missions

Over the past decade, the concept of using “offthe- shelf” Spacecraft (SC) buses for space science and earth science missions has become widespread. A “common bus” design approach has been used for Geosynchronous (GEO) communications satellites since the early 1970’s. The success of using common bus designs for the manufacture of GEO communications satellites is due to the commonality of mission requirements and orbit geometry. Science missions, on the other hand, each have unique mission and instrument payload requirements that can vary widely, encompassing orbit geometry, instrument type and configuration, science target, SC attitude, operations concept, and launch scenario. One of the most visible and successful implementations of “off-the-shelf” SC for science applications is the NASA Goddard Space Flight Center (GSFC) Rapid Spacecraft Development Office (RSDO) catalog, first released in 1997. In the current catalog (Rapid II), there are twenty-three different SC buses manufactured by eight aerospace companies. This paper provides a case study describing the adaptation of Spectrum Astro’s SA-200HP (High Performance) RSDO catalog SC bus to two very different Low Earth Orbiting (LEO) science missions, Coriolis and Swift, which were both procured via the RSDO. Coriolis is a Department-of-Defense-sponsored sunsynchronous earth observation satellite whose primary instrument, WindSat, is designed to precisely measure the ocean surface wind vector. Swift is a low inclination NASA Medium Explorer (MIDEX) mission to detect and characterize Gamma Ray Bursts (GRBs). The Swift Observatory carries three separate telescopes. In addition to describing how the catalog SC bus was applied to these missions, this paper discusses the unique features and benefits of the catalog bus approach to both the procuring agency and the industry bus provider. Misconceptions associated with the use of the catalog bus approach are also discussed

Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

Chronic neurohormonal and mechanical stresses are central fea-tures of heart disease. Increasing evidence supports a role forthe transient receptor potential canonical channels TRPC3 andTRPC6 in this pathophysiology. Channel expression for both is nor-mally very low but is increased by cardiac disease, and geneticgain- or loss-of-function studies support contributions to hypertro-phy and dysfunction. Selective small-molecule inhibitors remainscarce, and none target both channels, which may be useful giventhe high homology among them and evidence of redundant sig-naling. Here we tested selective TRPC3/6 antagonists (GSK2332255Band GSK2833503A; IC50,3–21 nM against TRPC3 and TRPC6) andfound dose-dependent blockade of cell hypertrophy signaling trig-gered by angiotensin II or endothelin-1 in HEK293T cells as well as inneonatal and adult cardiac myocytes. In vivo efficacy in mice andrats was greatly limited by rapid metabolism and high protein bind-ing, although antifibrotic effects with pressure overload were ob-served. Intriguingly, although gene deletion of TRPC3 or TRPC6alone did not protect against hypertrophy or dysfunction frompressure overload, combined deletion was protective, support-ing the value of dual inhibition. Further development of thispharmaceutical class may yield a useful therapeutic agent forheart disease management.Fil: Seo, Kinya. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Rainer, Peter P.. Johns Hopkins Medical Institutions. Department of Medicine; Estados Unidos. Medical University of Graz. Department of Medicine; AustriaFil: Shalkey Hahn, Virginia. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Lee, Dong-ik. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Jo, Su-Hyun. Kangwon National University School of Medicine; Corea del Sur. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Andersen, Asger. Aarhus University Hospital. Department of Cardiology; DinamarcaFil: Liu, Ting. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Xu, Xiaoping. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Willette, Robert N.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Lepore, John J.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Marino, Joseph P.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Birnbaumer, Lutz. ational Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Schnackenberg, Christine G.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Kass, David A.. Johns Hopkins Medical Institutions. Department of Medicine; Estados Unido

Impaired Notch Signaling Promotes \u3cem\u3eDe novo\u3c/em\u3e Squamous Cell Carcinoma Formation

Signaling through Notch receptors in the skin has been implicated in the differentiation, proliferation, and survival of keratinocytes, as well as in the pathogenesis of basal cell carcinoma (BCC). To determine the composite function of Notch receptor–mediated signaling in the skin and overcome potential redundancies between receptors, conditional transgenic mice were generated that express the pan-Notch inhibitor, dominant-negative Mastermind Like 1 (DNMAML1), to repress all canonical [CBF-1/Suppressor of hairless/LAG-1 (CSL)–dependent] Notch signaling exclusively in the epidermis. Here, we report that DNMAML1 mice display hyperplastic epidermis and spontaneously develop cutaneous squamous cell carcinoma (SCC) as well as dysplastic precursor lesions, actinic keratoses. Mice expressing epidermal DNMAML1 display enhanced accumulation of nuclear ß-catenin and cyclin D1 in suprabasilar keratinocytes and in lesional cells from SCCs, which was also observed in human cutaneous SCC. These results suggest a model wherein CSL-dependent Notch signaling confers protection against cutaneous SCC. The demonstration that inhibition of canonical Notch signaling in mice leads to spontaneous formation of SCC and recapitulates the disease in humans yields fundamental insights into the pathogenesis of SCC and provides a unique in vivo animal model to examine the pathobiology of cutaneous SCC and for evaluating novel therapies

Human Glial-Restricted Progenitor Transplantation into Cervical Spinal Cord of the SOD1G93A Mouse Model of ALS

Cellular abnormalities are not limited to motor neurons in amyotrophic lateral sclerosis (ALS). There are numerous observations of astrocyte dysfunction in both humans with ALS and in SOD1G93A rodents, a widely studied ALS model. The present study therapeutically targeted astrocyte replacement in this model via transplantation of human Glial-Restricted Progenitors (hGRPs), lineage-restricted progenitors derived from human fetal neural tissue. Our previous findings demonstrated that transplantation of rodent-derived GRPs into cervical spinal cord ventral gray matter (in order to target therapy to diaphragmatic function) resulted in therapeutic efficacy in the SOD1G93A rat. Those findings demonstrated the feasibility and efficacy of transplantation-based astrocyte replacement for ALS, and also show that targeted multi-segmental cell delivery to cervical spinal cord is a promising therapeutic strategy, particularly because of its relevance to addressing respiratory compromise associated with ALS. The present study investigated the safety and in vivo survival, distribution, differentiation, and potential efficacy of hGRPs in the SOD1G93A mouse. hGRP transplants robustly survived and migrated in both gray and white matter and differentiated into astrocytes in SOD1G93A mice spinal cord, despite ongoing disease progression. However, cervical spinal cord transplants did not result in motor neuron protection or any therapeutic benefits on functional outcome measures. This study provides an in vivo characterization of this glial progenitor cell and provides a foundation for understanding their capacity for survival, integration within host tissues, differentiation into glial subtypes, migration, and lack of toxicity or tumor formation