Construct validity of WAIS—R factors: Neuropsychological test correlates in adults referred for evaluation of possible head injury.

A 3-factor solution of the Wechsler Adult Intelligence Scale—Revised (WAIS—R; Wechsler, 1981) in 260 adults with suspected head injury suggested relatively good construct validity for the factors, based on correlations with neuropsychological tests purported to measure similar abilities. The Verbal Comprehension factor was related to verbal ability, verbal memory, and executive functioning. The Perceptual Organization factor, although measuring primarily visual–spatial perception and visual constructional ability, was related to visual–spatial memory, visual attention, and executive functioning. The Freedom From Distractibility factor was correlated with two attention measures and was not associated with memory measures. Its association with executive functioning was inconsistent. The findings are discussed in terms of the multidimensional nature of neuropsychological tests and WAIS—R factors. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Alterations in Protein Expression of Arabidopsis thaliana Cell Cultures During Hyper- and Simulated Micro-Gravity

Callus cell cultures of Arabidopsis thaliana exposed to hypergravity (8×g), 2D clinorotation and random positioning exhibit changes in gene expression (Martzivanou et al., Protoplasma 229:155–162, 2006). In a recent investigation we could show that after 2 h of exposure also the protein complement shows treatment-related changes which are indicative for reactive oxygen species being involved in the perception of/response to changes in the gravitational field. In the present study we have extended these investigations for a period of up to 16 h of exposure. We report on changes in abundance of 28 proteins which have been identified by nano HPLC-ESI-MS/MS, and which were altered in amount after 2 h of treatment. According to changes between 2 and 16 h we could distinguish four groups of proteins which either declined, increased from down-regulated to control levels, showed a transient decline or a transient increase. With regard to function, our data indicate stress relief or adaptation to a new gravitational steady state under prolonged exposure. The latter assumption is supported by the appearance of a new set of 19 proteins which is changed in abundance after 8 h of hypergravity. A comparative analysis of the different treatments showed some similarities in response between 8×g centrifugation and 2D clinorotation, while random positioning showed the least responses.     

Topography of brain sodium accumulation in progressive multiple sclerosis

Object

Sodium accumulation is involved in neuronal injury occurring in multiple sclerosis (MS). We aimed to assess sodium accumulation in progressive MS, known to suffer from severe neuronal injury.

Materials and methods

3D-²³Na-MRI was obtained on a 3T-MR-scanner in 20 progressive MS patients [11 primary-progressive (PPMS) and nine secondary-progressive (SPMS)] and 15 controls. Total sodium concentrations (TSC) within grey matter (GM), normal-appearing white matter (WM) and lesions were extracted. Statistical mapping analyses of TSC abnormalities were also performed.

Results

Progressive MS patients presented higher GM–TSC values (48.8 ± 3.1 mmol/l wet tissue vol, p < 0.001) and T₂lesions-TSC values (50.9 ± 2.2 mmol/l wet tissue vol, p = 0.01) compared to GM and WM of controls. Statistical mapping analysis showed TSC increases in PPMS patients confined to motor and somatosensory cortices, prefrontal cortices, pons and cerebellum. In SPMS, TSC increases were associated with areas involving: primary motor, premotor and somatosensory cortices; prefrontal, cingulate and visual cortices; the corpus callosum, thalami, brainstem and cerebellum. Anterior prefrontal and premotor cortices TSC were correlated with disability.

Conclusion

Sodium accumulation is present in progressive MS patients, more restricted to the motor system in PPMS and more widespread in SPMS. Local brain sodium accumulation appears as a promising marker to monitor patients with progressive MS.     

Development and characterization of inks for screen printing of glass solders for SOFCs

Glass ceramics are supposed to produce stable sealants between ceramic electrolyte and ferritic steel in planar SOFC stacks. The screen printing method is a suitable industrial process in order to produce layers with tailored height and width reproducibly. An appropriate suspension was developed for this application and improved by adjusting the additive composition. This study investigates the rheological behavior of screen printing inks and the corresponding topography of the printed layers. Rotary measurements were carried out to analyse the impact of shear rates on viscosity showing shear thinning behavior. In addition, oscillatory rheometry is performed to gain information about the viscoelastic properties of the slurries and to understand the internal structure of the developed inks. The viscoelasticity and the recovery behavior after shear loading are crucial for the topography of printed films. The principal investigations are executed on solvent-based suspensions, whereby the knowledge gained is used for a transfer to water-based systems allowing a more environmentally friendly handling.     

Targeted Synthesis of Complex Spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-ones by Intramolecular Cyclization of Azomethine Ylides: Highly Potent MDM2–p53 Inhibitors

Mouse double minute 2 (MDM2) is a main and direct inhibitor of the crucial tumor suppressor p53. Reports from initial clinical trials showed that blocking this interaction with a small-molecule inhibitor can have great value in the treatment of cancer for patients with p53 wild-type tumors; however, it also revealed dose-limiting hematological toxicities and drug-induced resistance as main issues. To overcome the former, an inhibitor with superior potency and pharmacokinetic properties to ultimately achieve full efficacy with less-frequent dosing schedules is required. Toward this aim, we optimized our recently reported spiro-oxindole inhibitors by focusing on the crucial interaction with the amino acid side chain of His96_MDM2. The designed molecules required the targeted synthesis of structurally complex spiro[indole-3,2′-pyrrolo[2,3-c]pyrrole]-2,4′-diones for which we developed an unprecedented intramolecular azomethine ylide cycloaddition and investigated the results by computational methods. One of the new compounds showed superior cellular potency over previously reported BI-0252. This finding is a significant step toward an inhibitor suitable to potentially mitigate hematological on-target adverse effects.     

Biocomposite films based on poly(lactic acid) and chitosan nanoparticles: Elaboration,microstructural and thermal characterization

Structured and fully bio‐based polymer assemblies based on chitosan micro‐ and nano‐particles and poly(lactic acid) (PLA) were developed using a continuous cast‐film extrusion process. The microstructure and thermal properties of the resulting biocomposite films are studied. Dispersion and size distribution of chitosan particles within the films were analyzed by optical microscopy and laser diffraction. Results show a homogeneous dispersion with no particles agglomeration, due to favorable physico–chemical interactions between chitosan particles and PLA and weak particle cohesion within the agglomerates. Differential scanning calorimetry experiments evidence a pronounced nucleating effect as well as an enhanced crystal growth rate, and a great increase in crystallinity of PLA in the presence of chitosan particles. Furthermore, in the case of chitosan nanoparticles, no reduction of PLA molecular weight occurred as revealed by gel permeation chromatography. The dispersion of nanosized chitosan particles in PLA thus appears to be an efficient way to control its crystallization behavior without degrading its molecular characteristics. POLYM. ENG. SCI., 59:E350–E360, 2019. © 2018 Society of Plastics Engineers     

The Human Host Defense Ribonucleases 1, 3 and 7 Are Elevated in Patients with Sepsis after Major Surgery—A Pilot Study

Sepsis is the most common cause of death in intensive care units and associated with widespread activation of host innate immunity responses. Ribonucleases (RNases) are important components of the innate immune system, however the role of RNases in sepsis has not been investigated. We evaluated serum levels of RNase 1, 3 and 7 in 20 surgical sepsis patients (Sepsis), nine surgical patients (Surgery) and 10 healthy controls (Healthy). RNase 1 and 3 were elevated in Sepsis compared to Surgery (2.2- and 3.1-fold, respectively; both p < 0.0001) or compared to Healthy (3.0- and 15.5-fold, respectively; both p < 0.0001). RNase 1 showed a high predictive value for the development of more than two organ failures (AUC 0.82, p = 0.01). Patients with renal dysfunction revealed higher RNase 1 levels than without renal dysfunction (p = 0.03). RNase 1 and 3 were higher in respiratory failure than without respiratory failure (p < 0.0001 and p = 0.02, respectively). RNase 7 was not detected in Healthy patients and only in two patients of Surgery, however RNase 7 was detected in 10 of 20 Sepsis patients. RNase 7 was higher in renal or metabolic failure than without failure (p = 0.04 and p = 0.02, respectively). In conclusion, RNase 1, 3 and 7 are secreted into serum under conditions with tissue injury, such as major surgery or sepsis. Thus, RNases might serve as laboratory parameters to diagnose and monitor organ failure in sepsis.     

Mild Stereoselective Intermolecular Acetoxylation and Azidation of α‐C−H Bonds in Tröger's Bases

Introduction of oxygen and nitrogen into organic molecules is one of the fundamental strategies for their functionalization. Traditional approaches rely on the formation of an activated intermediate, which is then modified in a subsequent step. Here we report a simple direct oxidative α‐acetoxylation and azidation of α‐C−H bonds in Tröger's base analogues promoted by N‐bromosuccinimide (NBS) and palladium(II)acetate [Pd(OAc)₂] under mild conditions. This approach is pivotal on NBS oxidizing the carbon atoms next to the nitrogen atoms in the presence of Pd(OAc)₂ followed by a reaction with oxygen‐ or nitrogen‐centred nucleophiles such as KOAc or NaN₃ to yield either the mono‐ and bisacetoxylated or azidated Tröger's base derivatives in a stereo‐ and chemoselective manner. The obtained products can be efficiently modified to access synthetically meaningful structures.

     

Trans-Splicing Improvement by the Combined Application of Antisense Strategies

Spliceosome-mediated RNA trans-splicing has become an emergent tool for the repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans-splicing molecules (RTMs) are designed to induce a specific trans-splicing reaction via a binding domain for a respective target pre-mRNA region. A previously established reporter-based screening system allows us to analyze the impact of various factors on the RTM trans-splicing efficiency in vitro. Using this system, we are further able to investigate the potential of antisense RNAs (AS RNAs), presuming to improve the trans-splicing efficiency of a selected RTM, specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB). We have shown that co-transfections of the RTM and a selected AS RNA, interfering with competitive splicing elements on a COL7A1-minigene (COL7A1-MG), lead to a significant increase of the RNA trans-splicing efficiency. Thereby, accurate trans-splicing between the RTM and the COL7A1-MG is represented by the restoration of full-length green fluorescent protein GFP on mRNA and protein level. This mechanism can be crucial for the improvement of an RTM-mediated correction, especially in cases where a high trans-splicing efficiency is required.     

Calcium silicate hydrate—in-situ development of the silicate structure followed by infrared spectroscopy

In the current study, the development of the silicate structure of synthetic calcium silicate hydrates with different calcium contents was followed by in-situ infrared (IR) spectroscopy and correlated to the in-situ phase development evaluated by X-ray diffraction (XRD). A baseline correction method initially developed for X-ray diffractograms was successfully adapted for the complex background of the fingerprint region in in-situ IR, which significantly contributed to signal quality and reproducibility. The development of separate silicate infrared bands could be monitored over 24 h of reaction. These bands could be assigned to oligomeric and dimeric species based on their time and stoichiometry-dependent development. It was clearly shown that the main peak of the dimeric silicate species was overlooked in the literature. The correlation of time-dependent events to in-situ XRD revealed that changes in the unit cell of calcium silicate hydrate are related to silicate polymerization. The results were compared to ²⁹Si-MAS-NMR, which highlighted the benefits of in-situ IR spectroscopy.