The Effect of Annealing on the Charge‐Carrier Dynamics in a Polymer/Polymer Bulk Heterojunction for Photovoltaic Applications

The effect of annealing blends of poly(2‐methoxy‐5‐(3′,7′‐dimethyloctyloxy)‐1,4‐phenylenevinylene) (MDMO‐PPV) and a poly(cyanoether phenylenevinylene) (PCNEPV) on the photoconductivity is studied. Charge carriers are generated by pulsed‐laser excitation and their mobility and decay kinetics are monitored using time‐resolved microwave conductivity (TRMC) measurements. Photoexcitation leads to the formation of an exciton, which can undergo charge separation at an interface between the electron‐donating MDMO‐PPV and the electron‐accepting PCNEPV. The electrons and holes formed in this way must escape from each other to contribute to the photoconductivity. The photoconductivity of the blends is found to increase by almost two orders of magnitude upon thermal annealing for three hours at 100 °C. This increase is attributed to the occurrence of phase separation in the polymer/polymer film, resulting in PCNEPV‐rich parts. The formation of PCNEPV‐rich parts allows the electron to diffuse away from the interface, which favors escape from geminate recombination, leading to a higher photoconductivity.     

Effect of pulse consumption on perceived flatulence and gastrointestinal function in healthy males

Despite their demonstrated health benefits, consumption of pulses in Western societies has traditionally been low. This is, in part, due to the perception that pulses cause flatulence and gastrointestinal upset. This randomized, double-blind placebo-controlled, cross-over study assessed the impact of 28 consecutive days consumption of 100 g dry weight Kabuli chickpeas, green Laird lentils, and green peas, in comparison to a potato control, on perceived flatulence, abdominal comfort, bowel movements and overall gastrointestinal function using a questionnaire with yes/no and visual analog rankings, in 21 healthy males between the ages of 19–40. Questionnaires were completed during three phases (PRE, EARLY, LATE) of each treatment period. Chi-square (occurrence) and Wilcoxon test (severity rank) analyses revealed minor changes in occurrence and/or severity of flatulence and abdominal comfort, but no changes in overall gastrointestinal function. These results demonstrate that pulses containing oligosaccharides are well tolerated with negligible perceived changes in flatulence and overall gastrointestinal function when incorporated into the diet of healthy adult males.     

Zafirlukast Induces VHL- and HIF-2α-Dependent Oxidative Cell Death in 786-O Clear Cell Renal Carcinoma Cells

Mutations in the Von Hippel–Lindau (VHL) gene are the driving force in many forms of clear cell renal cell carcinoma (ccRCC) and promote hypoxia-inducible factor (HIF)-dependent tumor proliferation, metastasis and angiogenesis. Despite the progress that has already been made, ccRCC generally remain resistant to conventional therapies and ccRCC patients suffer from metastasis and acquired resistance, highlighting the need for novel therapeutic options. Cysteinyl leukotriene receptor 1 (CysLTR1) antagonists, like zafirlukast, are administered in bronchial asthma to control eicosanoid signaling. Intriguingly, long-term use of zafirlukast decreases cancer risk and leukotriene receptor antagonists inhibit tumor growth, but the mechanisms still remain unexplored. Therefore, we aim to understand the mechanisms of zafirlukast-mediated cell death in ccRCC cells. We show that zafirlukast induces VHL-dependent and TNFα-independent non-apoptotic and non-necroptotic cell death in ccRCC cells. Cell death triggered by zafirlukast could be rescued with antioxidants and the PARP-1 inhibitor Olaparib, and additionally relies on HIF-2α. Finally, MG-132-mediated proteasome inhibition sensitized VHL wild-type cells to zafirlukast-induced cell death and inhibition of HIF-2α rescued zafirlukast- and MG-132-triggered cell death. Together, these results highlight the importance of VHL, HIF and proteasomal degradation in zafirlukast-induced oxidative cell death with potentially novel therapeutic implications for ccRCC.     

Four-Variable Model of an Enzymatic Oscillator Based on Trypsin

This paper describes a four-variable model for an enzymatic oscillator based on trypsin. Variables in this model are concentrations of the essential proteins (trypsin and trypsinogen) and small molecules (masked and active inhibitors of trypsin) within the network. Importantly, to simplify the model, non-essential side reactions are neglected and essential reactions are assumed to follow first or second order kinetics. Numerical solutions of this reduced model semi-quantitatively reproduce experimentally determined periods, amplitudes, and phase shifts of oscillations in the concentrations of several species in the network. Moreover, linear stability analysis shows that oscillations in the trypsin oscillator emerge and disappear through Hopf bifurcation. The model will be helpful in situations where simplicity is necessary such as detailed analysis of dynamics and modeling of reaction-diffusion systems.     

Simplified Monopalmitoyl Toll-like Receptor 2 Ligand Mini-UPam for Self-Adjuvanting Neoantigen-Based Synthetic Cancer Vaccines

Synthetic vaccines, based on antigenic peptides that comprise MHC−I and MHC-II T-cell epitopes expressed by tumors, show great promise for the immunotherapy of cancer. For optimal immunogenicity, the synthetic peptides (SPs) should be adjuvanted with suitable immunostimulatory additives. Previously, we have shown that improved immunogenicity in vivo is obtained with vaccine modalities in which an SP is covalently connected to an adjuvanting moiety, typically a ligand to Toll-like receptor 2 (TLR2). SPs were covalently attached to UPam, which is a derivative of the classic TLR2 ligand Pam₃CysSK₄. A disadvantage of the triply palmitoylated UPam is its high lipophilicity, which precludes universal adoption of this adjuvant for covalent modification of various antigenic peptides as it renders the synthetic vaccine insoluble in several cases. Here, we report a novel conjugatable TLR2 ligand, mini-UPam, which contains only one palmitoyl chain, rather than three, and therefore has less impact on the solubility and other physicochemical properties of a synthetic peptide. In this study, we used SPs that contain the clinically relevant neoepitopes identified in a melanoma patient who completely recovered after T-cell therapy. Homogeneous mini-UPam-SP conjugates have been prepared in good yields by stepwise solid-phase synthesis that employed a mini-UPam building block pre-prepared in solution and the standard set of Fmoc-amino acids. The immunogenicity of the novel mini-UPam-SP conjugates was demonstrated by using the cancer patient's T-cells.     

A linear translation from CTL* to the first-order modal μ -calculus

The modal μ-calculus is a very expressive temporal logic. In particular, logics such as LTL, CTL and CTL* can be translated into the modal μ-calculus, although existing translations of LTL and CTL* are at least exponential in size. We show that an existing simple first-order extension of the modal μ-calculus allows for a linear translation from LTL. Furthermore, we show that solving the translated formulae is as efficient as the best known methods to solve LTL formulae directly.     

Guarding against online threats: why entrepreneurs take protective measures

Information technology is becoming increasingly important for entrepreneurs. Protecting their technical infrastructure and stored data is, therefore, also becoming more vital. Nevertheless, research into the safety and security of entrepreneurs in general, and online threats targeted at entrepreneurs in particular, is still limited. This study investigates to what extent self-employed entrepreneurs protect themselves against online threats, and what motivates them to do so. Based on secondary analyses on data collected from 1622 Dutch entrepreneurs, we observe that the majority implement technical and personal coping measures. By adopting protection motivation theory as a theoretical basis for our study, we found that coping appraisal explains the adoption of protective measures. Entrepreneurs are likely to implement protective measures when they believe a measure is effective, when they are capable of using internet technology, when their attitude towards online protection is positive and when they believe they are responsible for their own online security. Although the secondary analysis provides some limitations, this study offers new insights into the usage of protective measures and the motivation for taking them. These insights can help to improve information security campaigns.     

Proteomic analysis of the response of the human neutrophil-like cell line NB-4 after exposure to anthrax lethal toxin

We used 2‐D DIGE to analyze the early response of NB‐4 cells, a human promyelotic leukemia cell line, exposed to lethal toxin from Bacillus anthracis at the proteome level. After a 2 h exposure, cells were still viable and 43% of spots (n = 1042) showed a significant change in protein level. We identified 59 spots whose expression had changed significantly, and these reflected cytoskeleton damage, mitochondrial lysis and endoplasmic reticulum stress. Actin filament assembly was disrupted as evidenced by an increase in both actin subunits and phosphorylated cofilin, whilst levels of tropomyosin, tropomodulin and actin related protein 2/3 complex subunit decreased. Lower levels of ATP synthase subunits and mitochondrial inner membrane protein were identified as markers of mitochondrial lysis. Levels of various stress response proteins rose and, uniquely, levels of Ca²⁺ binding proteins such as translationally controlled tumor protein rose and hippocalcin‐like protein 1 decreased. This response may have mitigated effects brought about by mitochondrial lysis and endoplasmic reticulum stress, and delayed or prevented apoptosis in NB‐4 cells. These results resemble findings of similar proteomics studies in murine macrophages, although quantitative differences were observed.     

Direction coding using a tactile chair

This laboratory study examined the possibility of using a car seat instrumented with a tactile display to communicate directional information to a driver. A car seat fitted with an 8 × 8 matrix of vibrators embedded in the seat pan was used to code eight different directions. Localization response time and angular accuracy were examined as a function of stimulus direction, presence of a tactile attention cue, temporal pattern, stimulus layout, age, and gender. The mean absolute angular error was 23°, and both localization accuracy and response times were superior for the back left, backward, and back right directions. Of the various temporal pattern/attention cue combinations examined, results favored the relatively fast patterns consisting of vibration bursts of 125 or 250 ms without a centrally located attention cue over 500 ms bursts that were preceded by an attention cue. Observed age and gender effects were relatively modest, suggesting that using tactile cueing to communicate direction is effective across a wide range of users. In addition, the tactile stimulus was detected by more than 90% of the participants under surprise trial conditions. Overall, these results indicate that the tactile chair provides a promising and robust method of providing directional information.     

Analysis of biofluids for biomarker research

While many of the developments made in high-throughput proteomics were originally applied to procaryotic and simple eucaryotic organisms, the analysis of biofluids became increasingly important as the prospect of using proteomics to discover novel biomarkers became realized. Biofluids have represented a unique challenge to proteomics as they are often present only in small amounts and, particularly in the cases of serum and plasma, can have protein concentration ranges that differ by ten orders of magnitude. While the discovery of authentic, clinically useful biomarkers in the proteomics era has been lacking, there have been a number of significant developments in the ability to more comprehensively characterize biofluid proteomes. The rapid pace of these developments suggest that the eventual discovery of clinically validate biomarkers using proteomic technologies still has a bright future.