Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Minimal invasive therapy of aneurysms of the superficial femoral artery and the popliteal artery

Percutaneous stent placement has been described for treatment of aneurysms as an alternative to surgical therapy. Literature reports of percutaneous minimal invasive therapy of peripheral aneurysms shall be reviewed and compared with our own results. Six male patients (51-69 years) with femoropopliteal occlusions related to aneurysms were treated percutaneously. In two cases Wallstents and in four cases polyester-covered nitinol stents were applicated. A clinical investigation including doppler-ultrasound was performed 24 hrs, 1, 3, 6, 12 and 24 months after the intervention. Stent placement succeeded in all cases. No adjunctive surgical treatment was necessary. Ankle-brachial-index (ABI) improved from 0.22 +/- 0.2 before to 0.74 +/- 0.2 24 hours after the intervention. One patient was lost for follow-up (Wallstent). A decrease of ABI and additional intraarterial angiography revealed stent-graft occlusion within one month (n = 2) and within three months (n = 1). One of these cases was successfully recanalized with local fibrinolysis therapy. In three patients patency of the stent persisted for 24 (+/- 2) months follow-up with three-vessel-supply of the calf. These results warrant further investigations for this minimal invasive method of percutaneous stent deployment as an alternative to surgical bypass treatment of femoropopliteal aneurysms. Time of hospitalization was reduced. At this time, surgical treatment of peripheral vascular aneurysms is gold standard.     

Gas-Liquid chromatography of fatty derivatives. I. Separation of homologous series ofa-olefins,n-hydrocarbons,n-nitriles,and n-alcohols

Summary Gas-liquid chromatography has been shown to be applicable to the analysis of several fatty derivatives. The difficulties inherent in conventional separation schemes such as liquid-liquid chromatography, fractional distillation, and crystallization can be overcome through the use of gas-liquid chromatography. It becomes the preferred procedure for several reasons: a) fractions are more nearly pure, b) analysis time is a fraction of the time required for conventional separations, c) operational procedures are simple and highly reproducible, d) sample size requirements are low, e) the cost per unit analysis is low. These factors suggest that gas-liquid chromatography is highly useful as an analytical tool in fat research. In many cases the determination of chainlength distribution has already become a routine function. There remain areas in which gas-liquid chromatography has not been completely successful. Until very recently the separation of fatty methyl esters of similar chain length and varying degrees of unsaturation has been time-consuming and tedious. Several new partitioning agents hold out great promise in the separation of the isomeric C₁₈ fatty acids. More selective partitioning agents and refined techniques undoubtedly will equally improve the resolution of unsaturated alcohols and other unsaturated fatty derivatives. Presented at annual meeting, American Oil Chemists' Society, Memphis, Tenn., April 21–23, 1958. Technical Paper No. 160, Archer-Daniels-Midland Company.     

Cross-Campus Collaboration to Produce Camtasia-Enhanced Lessons to Improve Distance Learning

This pilot study examines the use of Camtasia-enhanced lessons to supplement distance education provided to medical laboratory science students. More programs of study are available as distance learning opportunities, creating challenges to find better ways to present material. Librarians provided technical expertise necessary to produce a Camtasia video. This helped instructors prepare engaging lectures for phlebotomy to supplement the PowerPoint presentations and self-directed lessons provided in previous courses. Medical laboratory science faculty collaborated with library staff to produce videos that demonstrate proper phlebotomy technique using training personnel and faculty, whom the students eventually interact with in the clinical environment.     

Designing Personalized Garments with Body Movement

The standardized sizes used in the garment industry do not cover the range of individual differences in body shape for most people, leading to ill-fitting clothes, high return rates and overproduction. Recent research efforts in both industry and academia, therefore, focus on virtual try-on and on-demand fabrication of individually fitting garments. We propose an interactive design tool for creating custom-fit garments based on 3D body scans of the intended wearer. Our method explicitly incorporates transitions between various body poses to ensure a better fit and freedom of movement. The core of our method focuses on tools to create a 3D garment shape directly on an avatar without an underlying sewing pattern, and on the adjustment of that garment's rest shape while interpolating and moving through the different input poses. We alternate between cloth simulation and rest shape adjustment based on stretch to achieve the final shape of the garment. At any step in the real-time process, we allow for interactive changes to the garment. Once the garment shape is finalized for production, established techniques can be used to parameterize it into a 2D sewing pattern or transform it into a knitting pattern.     

Pressure dependence of superconductivity in Ba4C60

In Ba_xC₆₀ superconductivity (sc) at T_c=(6.8±0.2) K is associated with the x=4 phase. Here we present pressure studies of T_c of a Ba_xC₆₀ sample (dT_c/dp= –1.9 K/GPa) which exhibits a large volume fraction of the x=4 phase. In the alkali-fullerides K₆₀C₆₀ and Rb₃C₆₀ T_c is governed by the electronic density of states N(E_F) (T_c exp{–1/N(E_F)V}). The dependence of N(E_F) on volume can be approximated by N(E_F)=N₀ d _eff ³, where d_eff is the surface to surface distance of neighboured C₆₀-molecules. This relationship is corroborated by (T_C,d)-data of various compounds of the form A_3–xB_xC₆₀ (A: K, Rb; B: K, Rb, Cs; x2). Strong deviation from this behavior is found for the alkaline-fulleride superconductor Ba₄C₆₀. This deviation is attributed to the hybridization of alkaline-metal s-, d-states and C₆₀ -states.     

Evaluation of motor power cables for PWM AC drives

Three-phase power cables installed between the inverter and motor of AC motor drive systems have been mostly ignored in the years since AC drives have become widely accepted in industrial applications. However, power cable characteristics have become quite critical with the advent of faster inverter switching times, which have decreased by a factor of perhaps 20:1 in the last ten years. This paper describes the present areas of concern with regard to power cabling, as well as a test program to quantitatively evaluate power cable-related remedies for these problematic areas. A relative ranking of test results is developed comparing the eight power cable types tested. Cable connector considerations are examined, together with interconnection of the cable shield, or sheath, and the NEC ground circuits are discussed in light of the test results and recommendations presented. Power cable voltage ratings are discussed and recommendations made. A final cable total performance comparison, including installation factors, summarizes the paper