Development of a Novel Tool To Demystify Drug Distribution at Tissue-Blood Barriers

Tissue endothelial cells express ABC-transporter enzymes that change the concentration of small molecules within different tissue compartments. These “blood-tissue barriers” have been shown to directly affect the efficacy and toxicity of anticancer, antimicrobial, psychiatric, and anti-epileptic drugs. Currently this phenomenon is best studied for the blood-brain barrier, but remains enigmatic for most other tissues. In addition, canonical pharmacokinetic theory specifically assumes an equal concentration of free drug within all tissue compartments. Inspired by Lipinski's “rule of 5,” we here clarify current knowledge on drug–tissue distribution by: 1) curating the in-vivo literature on 73 drugs across 23 tissues and 2) developing two graphical web-based applications to visually describe and interpret data. These curated in-vivo dataset and visualization tools enabled us to achieve new insights into the logic of the barrier-tissue organization and showed remarkable correspondence to whole-body imaging of radiolabeled molecules.     

The relationship between work organization and workforce agility in small manufacturing enterprises

Organizational agility requires development of an adaptable workforce that is able to deal with unexpected and dynamic changes in the business environment. However, little research has been done on the attributes and characteristics of workforce agility. Even less is known about what organization characteristics are conducive to the agile performance of employees. The main goal of this study was to explore the effect of agile strategies on work organization and employees' performance. A total of 41 managers, 82 office workers, and 52 production workers from six small manufacturing companies participated in the study. Three questionnaires, including Agility Strategy Scale, Work Organization Scale, and Workforce Agility Scale, were used for the purpose of data collection. The results support a hypothesized relationship between management strategies focused on agility development, work characteristics, and workforce agility. The results also reveal that autonomy at work is one of the most important predictors of workforce agility. A combination of job demands and job uncertainty had a significant effect on workforce agility. The study also suggests that developing strong cooperative relationships within an organization and with customers and suppliers promotes workforce agility in small manufacturing enterprises.     

Highly Substituted Carboxymethyl Starch

Carboxymethyl starches (CMS) with a degree of substitution (DS) in the range of 0.5 to 1.5 and reagent yields about 70% were synthesised under heterogeneous reaction conditions. Starting from a standard procedure for manufacturing low substituted CMS the molar ratios of the reagents were increased. Under these conditions starch particles agglomerated during the reaction and the stirrer stopped. The reaction conditions (pulp density, addition of dispersing and water binding agents, pressure, sequence of reagents addition, reaction time, temperature, starch variety, etc.) were varied to find the best process conditions for optimum reaction efficiencies and product properties. If an amylose‐free starch, e.g. waxy corn starch is used as starting material, the obtained products are completely soluble in water to form a clear solution. The products are good viscosity regulators. Using a 2% aqueous solution a wide range of viscosity (1–90 000 mPa s) can be adjusted. The calcium‐binding capacity and the biodegradability of the products were investigated.     

Activation parameters and excitation yields of 1,2-dioxetanes of photogenotoxic interest

The chemiluminescent decomposition of functionalized 1,2-dioxetanes was examined in toluene solution. Activation energies were measured by isothermal and nonisothermal kinetic methods. Quantum efficiencies were determined by Stern-Volmer kinetics, using the fluorescers 9,10-dibromo- and 9,10-diphenylanthracene for the triplet and singlet excitation yields. The derivatives of 3-hydroxymethyl-3,4,4-trimethyl-1,2-dioxetane ( 1a ) have free energies of activation (ΔG^≠) of ca. 25 kcal/mol, but the ΔG^≠ values of the annelated benzofuran-type dioxetanes ( 5 ) are ca. 1 kcal/mol lower. There exists a reasonable correlation between the free energies of activation (ΔG^≠) for the thermal decomposition of the dioxetanes and their triplet excitation flux (E_p^T).     

Hydrolysis of polyhydroxy polyunsaturated fatty acid-glycerophosphocholines by Group IIA,V, and X secretory phospholipases A2

It is widely accepted that unesterified polyunsaturated ω-6 and ω-3 fatty acids (PUFA) are converted through various lipoxygenases, cyclooxygenases, and cytochrome P450 enzymes to a range of oxygenated derivatives (oxylipins), among which the polyhydroxides of unesterified PUFA have recently been recognized as cell signaling molecules with anti-inflammatory and pro-resolving properties, known as specialized pro-resolving mediators (SPMs). This study investigates the mono-, di-, and trihydroxy 16:0/PUFA-GPCs, and the corresponding 16:0/SPM-GPC, in plasma lipoproteins. We describe the isolation and identification of mono-, di-, and trihydroxy AA, EPA, and DHA-GPC in plasma LDL, HDL, HDL3, and acute phase HDL using normal phase LC/ESI-MS, as previously reported. The lipoproteins contained variable amounts of the polyhydroxy-PUFA-GPC (0–10 nmol/mg protein), likely the product of lipid peroxidation and the action of various lipoxygenases and cytochrome P450 enzymes on both free fatty acids and the parent GPCs. Polyhydroxy-PUFA-GPC was hydrolyzed to variable extent (20%–80%) by the different secretory phospholipases A₂ (sPLA₂s), with Group IIA sPLA₂ showing the lowest and Group X sPLA₂ the highest activity. Surprisingly, the trihydroxy-16:0/PUFA-GPC of APHDL was largely absent, while large amounts of unidentified material had migrated in the free fatty acid elution area. The free fatty acid mass spectra were consistent with that anticipated for branched chain polyhydroxy fatty acids. There was general agreement between the masses determined by LC/ESI-MS for the polyhydroxy PUFA-GPC and the masses calculated for the GPC equivalents of resolvins, protectins, and maresins using the fatty acid structures reported in the literature.     

圆筒实验数据研究高能炸药的爆轰特性（英）

根据圆筒实验数据,采用新方法计算了HMX、RDX、PETN、TNT等炸药的爆轰能,研究了爆轰产物的加速能力,并与CHEETAH的计算结果进行了对比。通过爆轰波在柱壳水介质中传播的圆筒实验方法,预估了炸药的爆压。利用实验和热化学计算的结果推导了JWL状态方程的待定常数,并依据JWL等熵线计算了做功能力。