Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

Bayes estimation of the linear hazard-rate model

In life testing, the failure-time distributions are often specified by choosing an appropriate hazard-rate function. The class of life-time distribution characterized by a linear hazard-rate includes the one-parameter exponential and Rayleigh distributions. Usually the parameters of the linear hazard-rate model are estimated by the method of least squares. This work is concerned with Bayes estimation of the two-parameters from a type-2 censored sample. Monte Carlo simulation is used to compare the Bayes risk of the regression estimator with the minimum Bayes risk. Discrete mixtures of decreasing failure rate distributions are known to have decreasing failure rates. The authors prove that the result holds for continuous mixtures as well     

The mouse homolog of the human Miller-Dieker chromosomal region (MDCR) maps to mouse chromosome 11 in close proximity to Mov9 and D11Nds1

Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 have been shown to stimulate the synthesis of acute-phase proteins; however, few studies have examined the effect of these cytokines on gluconeogenesis. We investigated the effects of these cytokines on gluconeogenesis in primary cultures of rat hepatocytes. Incubation of hepatocytes for 24 hours with TNF-alpha or IL-1 alpha did not affect gluconeogenesis. Hepatocytes incubated with 100 pmol/L and 1 nmol/L IL-6 had a dose-dependent increase (P < .05) in gluconeogenesis (2.6 +/- 0.1 and 3.2 +/- 0.1 pmol/10(6) cells/min, respectively) as compared with controls (2.0 +/- 0.1).     

A Bethe theory for the directional dependence of stopping by molecules

We derive a Bethe formula for the stopping of swift ions by target molecules oriented with respect to the beam. The theory is characterized by a directional mean excitation energy formed from transition energies and dipole matrix elements. The expression for the mean excitation energy is similar to the one for an isotropic sample but the dipole matrix elements corresponding to the various transition moment directions carry unequal weights which depend on the orientation of the molecule with respect to the beam. For a large class of molecules, the logarithm of the mean excitation energy is linear in sin² θ, where θ denotes the angle between the beam and the principal molecular axis. We illustrate the properties of the theory in the simple case of a diatomic molecule.     

Group codes on certain algebraic curves with many rational points

We construct a series of algebraic geometric codes using a class of curves which have many rational points. We obtain codes of lengthq ² over _q , whereq = 2q ₀ ² andq ₀ = 2 ⁿ , such that dimension + minimal distance q ² + 1 – q ₀ (q – 1). The codes are ideals in the group algebra _q [S], whereS is a Sylow-2-subgroup of orderq ² of the Suzuki-group of orderq ² (q ² + 1)(q – 1). The curves used for construction have in relation to their genera the maximal number of GF _q -rational points. This maximal number is determined by the explicit formulas of Weil and is effectively smaller than the Hasse—Weil bound.Supported by Deutsche Forschungsgemeinschaft while visiting Essen University     

Comparison of different methods to determine the spreadability and firmness of processed cheese

Summary Current texture-measuring instruments and a recently developed measuring method (two-dimensional measuring of the force necessary to spread a sample) were compared in measuring the spreadability of processed cheese. How far subjective assessment by a qualified panel correlates with the instrumental results in determining spreadability and firmness was also investigated. Samples of processed cheese with various consistencies were measured by an Universal testing machine, a buttermeasuring instrument (DIN 10331), a rotational-type rheometer (oscillation mode) and a two-dimensional force measuring instrument. The evaluation of the results shows that an oscillating rheometer is most suitable to measure the spreadability of processed cheese; the correlation coefficient (r) between the dynamic Weissenberg number, calculated from parameters of the rheometer, and the subjective judgement by the panel wasr=0.91. For the determination of firmness the two-dimensional force measuring instrument is most suitable. The correlation coefficient between the parameter tangential energy (S _t) and the sensorially evaluated firmness wasr=0.95.

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Vergleich verschiedener Bestimmungsmethoden für die Streichfähigkeit und Festigkeit von Schmelzkäse

Zusammenfassung Verschiedene gebräuchliche Meßinstrumente und ein neu entwickeltes Gerät zur zweidimensionalen Messung der Kräfte, die zum Ausstreichen einer Probe erforderlich sind, wurden vergleichend zur Charakterisierung der Streichfähigkeit von Schmelzkäse erprobt. Dabei wurde auch geprüft, inwieweit die subjektiven Beurteilungen eines qualifizierten Prüferpanels mit den Meßwerten für Streichfähigkeit und Festigkeit korrelierten. Gemessen wurde mit einer Universalprüfmaschine, dem Butterprüfgerät (DIN 10331), einem Rotationsrheometer und mit dem zweidimensional registrierenden Kraftmeßgerät. Dabei zeigte sich, daß das Rheometer im oscillierenden Modus die Streichfähigkeit am besten zu charakterisieren vermag. Die Korrelation zwischen den Rheometerwerten, berechnet als dynamische Weissenbergzahl, und den sensorisch ermittelten Werten für die Streichfähigkeit betrugr=0,91. Zur Bestimmung der Festigkeit ist das zweidimensional registrierende Kraftmeßgerät am besten geeignet, was sich in einem Korrelationskoeffizienten vonr=0,95 zwischen dem ParameterS _t und den im Sensoriktest ermittelten Werten für dieFestigkeit ausdrückt.

     

Overview of Tiber-II—Evolution toward an Engineering Test Reactor

TIBER II is designed to be a minimum size and cost candidate for an international Engineering Test Reactor. High-current density Nb₃Sn superconducting magnets with radiation-tolerant polymide insulation is combined with a minimum thickness tungsten inbored shield and a common, external vacuum boundary to minimize the inner radial build of the tokamak core. This results in a major radius of 3 m, compared to 5 m for previous ETR designs such as INTOR, with correspondingly lower costs expected. Cyclic stress fatigue limits the number of pulses so that steady-state current drive, based on a combination of neutral beams, lower hybrid and ECH, is designed to achieve reactor-relevant nuclear testing conditions (Fluence 3MW yr/m², rwall > 1 MW/m² in steady state).This report is abstracted from a more complete information document UCID-20863 with numerous authors. See Ref. l for complete credits.     

Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.