Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73⁺ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73⁺ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73⁺ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73⁺ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.     

The oxidation of benzene under conditions encountered in waste incinerators

The oxidation of benzene was studied as a function of residence time (τ_res=0–2.5 s), temperature (850–960 K), and oxygen concentration (O₂=0.2–2.3%) in a heated laminar flow reactor at atmospheric pressure. Nitrogen, doped with 350 ppm benzene, was injected downstream of the burned gas from a near stoichiometric flame of methane + air. Gas samples were taken at different heights up the reactor and analyzed using GC-FID/TCD and HPLC techniques. Phenol and partially oxidized hydrocarbons such as acetaldehyde, formaldehyde, and acrolein were found with concentrations up to 50 ppm. At relatively low temperatures, the conversion of benzene was observed to proceed considerably more slowly at higher oxygen concentrations. Measured concentration profiles were modeled using detailed reaction schemes. A modified mechanism for the oxidation of benzene called BenWas was constructed from the mechanism of Zhang and McKinnon (Combust. Sci. Technol. 107 (1995) 261) by incorporating a submechanism for benzoquinone (OC₆H₄O) and by updating and enlarging the reaction scheme of cyclopentadiene (C₅H₆). The agreement between observed and predicted concentration profiles, e.g., of phenol (C₆H₅OH), acetylene (C₂H₂), and carbon monoxide (CO), was considerably improved by the use of the BenWas mechanism for rich and lean conditions, mainly due to the introduction of an additional pathway for phenyl oxidation (C₆H₅ + O₂ = OC₆H₄O + H) and due to the changed kinetics of the oxidation of cyclopentadienyl (C₅H₅) in C₅H₅ + O₂ = C₅H₄O + OH. The measured retardation of benzene oxidation with higher amounts of oxygen can be explained by the formation and reactions of peroxy radicals.     

Insights into the In Vitro Formation of Apatite from Mg-Stabilized Amorphous Calcium Carbonate

A protein-free formation of bone-like apatite from amorphous precursors through ball-milling is reported. Mg²⁺ ions are crucial to achieve full amorphization of CaCO₃. Mg²⁺ incorporation generates defects which strongly retard a recrystallization of ball-milled Mg-doped amorphous calcium carbonate (BM-aMCC), which promotes the growth of osteoblastic and endothelial cells in simulated body fluid and has no effect on endothelial cell gene expression. Ex situ snapshots of the processes revealed the reaction mechanisms. For low Mg contents (<30%) a two phase system consisting of Mg-doped amorphous calcium carbonate (ACC) and calcite “impurities” was formed. For high (>40%) Mg²⁺ contents, BM-aMCC follows a different crystallization path via magnesian calcite and monohydrocalcite to aragonite. While pure ACC crystallizes rapidly to calcite in aqueous media, Mg-doped ACC forms in the presence of phosphate ions bone-like hydroxycarbonate apatite (dahllite), a carbonate apatite with carbonate substitution in both type A (OH⁻) and type B (PO₄³⁻) sites, which grows on calcite “impurities” via heterogeneous nucleation. This process produces an endotoxin-free material and makes BM-aMCC an excellent “ion storage buffer” that promotes cell growth by stimulating cell viability and metabolism with promising applications in the treatment of bone defects and bone degenerative diseases.     

Capacity-achieving probability measure for a reduced number of signaling points

Putting bounding constraints on the input of a channel leads in many cases to a discrete capacity-achieving distribution with a finite support. Given a finite number of signaling points, we determine reduced subsets and the corresponding optimal probability measures to simplify the receiver design. The objective for the subset selection is to keep the channel quality high by maximizing mutual information and cutoff rate. Two approaches are introduced to obtain a capacity-achieving probability measure for the reduced subset. The first one is based on a preceded signaling point selection while the second one chooses the signaling points and corresponding probabilities simultaneously. Numerical results for both approaches show that using only a small number of signaling points achieves a very high mutual information compared to channels utilizing the full set of signaling points.     

Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Argon belongs to the group of noble gases, which are regarded as chemically inert. Astonishingly some of these gases exert biological properties and during the last decades more and more reports demonstrated neuroprotective and organoprotective effects. Recent studies predominately use in vivo or in vitro models for ischemic pathologies to investigate the effect of argon treatment. Promising data has been published concerning pathologies like cerebral ischemia, traumatic brain injury and hypoxic ischemic encephalopathy. However, models applied and administration of the therapeutic gas vary. Here we provide a systematic review to summarize the available data on argon’s neuro- and organoprotective effects and discuss its possible mechanism of action. We aim to provide a summary to allow further studies with a more homogeneous setting to investigate possible clinical applications of argon.     

Processing behavior and mechanical properties of autopolymerizing hypoallergenic denture base polymers

Driven by the phenomenon of increasing irritations and allergic reactions of dental prosthesis carriers preferably due to residual methyl methacrylate monomer in conventional dental materials, autopolymerizing hypoallergenic denture base polymers were prepared as two‐component materials in the shape of paste/paste‐ or powder/liquid systems. The processing behavior of these materials was investigated regarding the processing and solidification times also in dependence on the polymerization catalyst concentration, whereas the whole processing and curing characteristics and the final polymer properties were evaluated by dynamic mechanical analysis in shear mode in the temperature range from ?145°C to 200°C. The mechanical properties of the hypoallergenic denture base polymers were validated regarding stiffness (flexural modulus E') and fracture toughness (maximum factor of loading intensity , total work of fracture ) and the effects of monomer composition, kind of resin powder, impact modification by the liquid component, and water immersion on these properties were investigated. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41378.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Site-selective substitution and resulting magnetism in arc-melted perovskite ATiO3-δ (A = Ca,Sr, Ba)

Magnetic properties in perovskite titanates ATiO_3-δ (A = Ca, Sr, Ba) were investigated before and after arc melting. Crystal structure analysis was conducted by powder synchrotron X-ray diffraction with Rietveld refinements. Quantitative chemical element analysis was carried out by X-ray photoelectron spectroscopy. Magnetic measurements were conducted by vibrating sample magnetometer and X-ray magnetic circular dichroism (XMCD). The magnetic properties are found to be affected by impurities of 3d elements such as Fe, Co, and Ni. Depending on the composition and crystal structure, the occupation of the magnetic ions in perovskite titanates is selectively varied, which is interpreted to be the origin of the different magnetic behaviors in arc-melted perovskite titanates ATiO_3-δ (A = Ca, Sr, Ba). In addition, both formation of oxygen vacancies and the reduction of Ti⁴⁺ to Ti³⁺ during arc-melting also play a role as proven by XMCD. Nevertheless, preferential site occupation of magnetic impurities is dominant in the magnetic properties of arc-melted perovskite ATiO_3-δ (A = Ca, Sr, Ba).     

Inhibitors of inducible NO synthase expression: total synthesis of (S)-curvularin and its ring homologues

(S)-Curvularin and its 13-, 14-, and 16-membered lactone homologues were synthesized through a uniform strategy in which a Kochi oxidative decarboxylation and ring-closing metathesis reactions constitute the key processes. In the evaluation of the anti-inflammatory effects of the synthesized compounds in assays using cells stably transfected with a human iNOS promoter-luciferase reporter gene construct, the 14- and 16-membered homologues showed a slightly higher inhibitory effect towards iNOS promoter activity than curvularin itself. However, the larger ring homologues also exhibited higher cytotoxicity, manifest in downregulated eNOS promoter activity. In contrast, the di-O-acetyl and 4-chloro derivatives of (S)-curvularin showed higher inhibitory efficiency towards induction of the iNOS promoter and less negative effect on eNOS promoter activity than curvularin.