Pressure and Motion of Dry Sand -- Translation of Hagen's Paper from 1852

In a remarkable paper from 1852, Gotthilf Heinrich Ludwig Hagen measured and explained two fundamental aspects of granular matter: The first effect is the saturation of pressure with depth in a static granular system confined by silo walls -- generally known as the Janssen effect. The second part of his paper describes the dynamics observed during the flow out of the container -- today often called the Beverloo law -- and forms the foundation of the hourglass theory. The following is a translation of the original German paper from 1852.Comment: 4 pages, accepted for publication in Granular Matter, original article (German) can be found under http://www.phy.duke.edu/~msperl/Janssen

Development of a Cofactor Balanced, Multi Enzymatic Cascade Reaction for the Simultaneous Production of L-Alanine and L-Serine from 2-Keto-3-deoxy-gluconate

Enzymatic reaction cascades represent a powerful tool to convert biogenic resources into valuable chemicals for fuel and commodity markets. Sugars and their breakdown products constitute a significant group of possible substrates for such biocatalytic conversion strategies to value-added products. However, one major drawback of sugar cascades is the need for cofactor recycling without using additional enzymes and/or creating unwanted by-products. Here, we describe a novel, multi-enzymatic reaction cascade for the one-pot simultaneous synthesis of L-alanine and L-serine, using the sugar degradation product 2-keto-3-deoxygluconate and ammonium as precursors. To pursue this aim, we used four different, thermostable enzymes, while the necessary cofactor NADH is recycled entirely self-sufficiently. Buffer and pH optimisation in combination with an enzyme titration study yielded an optimised production of 21.3 +/− 1.0 mM L-alanine and 8.9 +/− 0.4 mM L-serine in one pot after 21 h

Development of an improved peroxidase-based high-throughput screening for the optimization of D-glycerate dehydratase activity

Successful directed evolution examples span a broad range of improved enzyme properties. Nevertheless, the most challenging step for each single directed evolution approach is an efficient identification of improved variants from a large genetic library. Thus, the development and choice of a proper high-throughput screening is a central key for the optimization of enzymes. The detection of low enzymatic activities is especially complicated when they lead to products that are present in the metabolism of the utilized genetic host. Coupled enzymatic assays based on colorimetric products have enabled the optimization of many of such enzymes, but are susceptible to problems when applied on cell extract samples. The purpose of this study was the development of a high-throughput screening for D-glycerate dehydratase activity in cell lysates. With the aid of an automated liquid handling system, we developed a high-throughput assay that relied on a pre-treatment step of cell extract prior to performing the enzymatic and assay reactions. We could successfully apply our method, which should also be transferable to other cell extract-based peroxidase assays, to identify an improved enzyme for the dehydration of D-glycerate

Impact of Generalist Care Managers on Patients with Diabetes

OBJECTIVE: To determine how the addition of generalist care managers and collaborative information technology to an ambulatory team affects the care of patients with diabetes. STUDY SETTING: Multiple ambulatory clinics within Intermountain Health Care (IHC), a large integrated delivery network. STUDY DESIGN: A retrospective cohort study comparing diabetic patients treated by generalist care managers with matched controls was completed. Exposure patients had one or more contacts with a care manager; controls were matched on utilization, demographics, testing, and baseline glucose control. Using role-specific information technology to support their efforts, care managers assessed patients' readiness for change, followed guidelines, and educated and motivated patients. DATA COLLECTION: Patient data collected as part of an electronic patient record were combined with care manager-created databases to assess timely testing of glycosylated hemoglobin (HbA1c) and low-density lipoprotein (LDL) levels and changes in LDL and HbA1c levels. PRINCIPAL FINDINGS: In a multivariable model, the odds of being overdue for testing for HbA1c decreased by 21 percent in the exposure group (n=1,185) versus the control group (n=4,740). The odds of being tested when overdue for HbA1c or LDL increased by 49 and 26 percent, respectively, and the odds of HbA1c <7.0 percent also increased by 19 percent in the exposure group. The average HbA1c levels decreased more in the exposure group than in the controls. The effect on LDL was not significant. CONCLUSIONS: Generalist care managers using computer-supported diabetes management helped increase adherence to guidelines for testing and control of HbA1c levels, leading to improved health status of patients with diabetes