Immune Aging and Immunotherapy in Cancer

Immune functions decline as we age, while the incidence of cancer rises. The advent of immune checkpoint blockade (ICB) has not only revolutionized cancer therapy, but also spawned great interest in identifying predictive biomarkers, since only one third of patients show treatment response. The aging process extensively affects the adaptive immune system and thus T cells, which are the main target of ICB. In this review, we address age-related changes regarding the adaptive immune system with a focus on T cells and their implication on carcinogenesis and ICB. Differences between senescence, exhaustion, and anergy are defined and current knowledge, treatment strategies, and studies exploring T cell aging as a biomarker for ICB are discussed. Finally, novel approaches to improve immunotherapies and to identify biomarkers of response to ICB are presented and their potential is assessed in a comparative analysis.     

Synthesis and conductivities of (μ-cyano)phthalocyaninatometal compounds

A review of the synthesis and characterization of a new type of stacked, bridged macrocyclic metal complexes, the (μ-cyano)phthalocyaninatometal compounds [PcMCN]_n (2) is given. By using the routes described in Fig. 3 the polymers were synthesized with M = Co³⁺, Fe²⁺, Fe³⁺, Mn³⁺ and Cr³⁺ as the central metal ion. The compounds were characterized by IR, far-IR, UV, thermal and elemental analysis, and partly by ¹H NMR and FD (field desorption) mass spectroscopy.[PcCoCN] (2a) and [PcFeCN]_n (2b) exhibit d.c. room temperature conductivities around 10^?2 S/cm without doping, thereby showing conductivities which are in the same range as the iodine-doped phthalocyaninatosiloxanes [PcSiO]_n.     

Polyplexes of polyethylenimine and per-N-methylated polyethylenimine-cytotoxicity and transfection efficiency

For non-viral gene delivery, the carriers for DNA transfer into cells must be vastly improved. The branched cationic polymer polyethylenimine has been described as an efficient gene carrier. However, polyethylenimine was demonstrated to mediate substantial cytotoxicity. Therefore, this study is aimed at investigating per-N-methylated polyethylenimine, which is thought to have a much lower cytotoxicity due to its lower charge density. Results from a gel retardation assay and laser light scattering indicated that per-N-methylated polyethylenimine condenses DNA into small and compact nanoparticles with a mean diameter <150 nm. Furthermore, polyplexes of polyethylenimine and per-N-methylated polyethylenimine with DNA had a positive zeta potential and the polymers protected DNA from nuclease-mediated digestion. The transfection efficiency of polyethylenimine and per-N-methylated polyethylenimine was tested in CHO-K1 cells. Using green fluorescent protein as reporter gene and flow cytometry analysis, we demonstrated that per-N-methylated polyethylenimine has a lower cytotoxicity, but also a significantly lower transfection efficiency. Using propidium iodide staining, we could additionally distinguish between viable and dead cells. At NP > or = 12, per-N-methylated polyethylenimine showed a much higher cell viability and the ratio of viable and transfected cells to dead and transfected cells was about 1.5 to 1.7 fold higher than for polyethylenimine. The results of cell viability from flow cytometry analysis were confirmed by the MTS assay. Using luciferase reporter gene for transfection experiments, the gene expression of per-N-methylated polyethylenimine was lower at NP 6, 12 and 18 as compared to polyethylenimine, but at NP 24 it yielded similar levels.     

A stereophonic acoustic signal extraction scheme for noisy and reverberant environments

In this contribution, a novel two-channel acoustic front-end for robust automatic speech recognition in adverse acoustic environments with nonstationary interference and reverberation is proposed. From a MISO system perspective, a statistically optimum source signal extraction scheme based on the multichannel Wiener filter (MWF) is discussed for application in noisy and underdetermined scenarios. For free-field and diffuse noise conditions, this optimum scheme reduces to a Delay & Sum beamformer followed by a single-channel Wiener postfilter. Scenarios with multiple simultaneously interfering sources and background noise are usually modeled by a diffuse noise field. However, in reality, the free-field assumption is very weak because of the reverberant nature of acoustic environments. Therefore, we propose to estimate this simplified MWF solution in each frequency bin separately to cope with reverberation. We show that this approach can very efficiently be realized by the combination of a blocking matrix based on semi-blind source separation (‘directional BSS’), which provides a continuously updated reference of all undesired noise and interference components separated from the desired source and its reflections, and a single-channel Wiener postfilter. Moreover, it is shown, how the obtained reference signal of all undesired components can efficiently be used to realize the Wiener postfilter, and at the same time, generalizes well-known postfilter realizations. The proposed front-end and its integration into an automatic speech recognition (ASR) system are analyzed and evaluated in noisy living-room-like environments according to the PASCAL CHiME challenge. A comparison to a simplified front-end based on a free-field assumption shows that the introduced system substantially improves the speech quality and the recognition performance under the considered adverse conditions.     

Evidence for organosulfates in secondary organic aerosol

Recent work has shown that particle-phase reactions contribute to the formation of secondary organic aerosol (SOA), with enhancements of SOA yields in the presence of acidic seed aerosol. In this study, the chemical composition of SOA from the photooxidations of alpha-pinene and isoprene, in the presence or absence of sulfate seed aerosol, is investigated through a series of controlled chamber experiments in two separate laboratories. By using electrospray ionization-mass spectrometry, sulfate esters in SOA produced in laboratory photooxidation experiments are identified for the first time. Sulfate esters are found to account for a larger fraction of the SOA mass when the acidity of seed aerosol is increased, a result consistent with aerosol acidity increasing SOA formation. Many of the isoprene and alpha-pinene sulfate esters identified in these chamber experiments are also found in ambient aerosol collected at several locations in the southeastern U.S. It is likely that this pathway is important for other biogenic terpenes, and may be important in the formation of humic-like substances (HULIS) in ambient aerosol.